Skip to main content
UploadLanguage (EN)Support
BusinessMobileSocial MediaMarketingTechnologyArt & PhotosCareerDesignEducationPresentations & Public SpeakingGovernment & NonprofitHealthcareInternetLawLeadership & ManagementAutomotiveEngineeringSoftwareRecruiting & HRRetailSalesServicesScienceSmall Business & EntrepreneurshipFoodEnvironmentEconomy & FinanceData & AnalyticsInvestor RelationsSportsSpiritualNews & PoliticsTravelSelf ImprovementReal EstateEntertainment & HumorHealth & MedicineDevices & HardwareLifestyle
Uploaded bythekashmedico
39,717 views

Pharmacology_RR.pdf by Dr Gobind Rai Garg

The document covers essential concepts of pharmacology, focusing on pharmacokinetics (ADME: absorption, distribution, metabolism, excretion) and pharmacodynamics (drug action mechanisms). Key points include the significance of bioavailability, the role of enzymes in drug metabolism, various drug classifications, and the effects of drug interactions. It also highlights clinical trial phases, regulatory aspects, and the prescription writing guidelines.

Education◦
Downloaded 423 times
Pharmacology Quick Revision Notes
Pharmacology is the science dealing with drugs. Two branches: 1. PharmacoKinetics → Effect of Body on Drug 2.PharmacoDynamics → Effect of Drug on Body PHARMACOKINETICS • • Aka ADME Study – – Absorption – – Distribution – – Metabolism – – Excretion 1. Absorption • • It is the movement of drug from site of administration to blood. • • Lipid Solubility is the most important factor in absorption.Q When The Medium Is Same, Then The Drug Will Cross DRUG MEDIUM FORM SOLUBILITY CROSS Acidic Basic Acidic Basic Acidic Basic Basic Acidic Non ionized Non ionized lonized lonized Lipid Soluble Lipid soluble Water Soluble Water Soluble   x x Bioavailability • • It is the fraction of given dose that reaches the systemic circulation in unchanged form Factors affecting: 1. Absorption → Absorption → ↑ Bioavailability Chapter - 1 General Pharmacology ↓ Absorption → ↓ Bioavailability 2. First Pass metabolism/Pre systemic metabolism ↑ First Pass metabolism → ↓ Bioavailability ↓ First Pass metabolism → ↓ Bioavailability Note: If we give a drug by IV route, bioavailability is 100%Q Plasma Concentration Vs Time Graph Cmax Maximum concentration obtained by a particular dose Should lie between MTC and MEC Tmax Time in which plasma concentration becomes maximum Tells Rate of absorption AUC Total area covered by graphQ Tells Extent of absorption 2. Distribution • • Distribution is a measure of amount of drug in tissues after absorption in the systemic circulation • • It depends upon lipid solubility and plasma protein binding. Plasma Protein BindingQ • • Acidic drugs bind to → Albumin • • Basic drugs bind to → a1 Acid Glycoprotein High PPB drugs have • • Low Vd • • Long duration of action • • More drug interactions • • Dialysis not useful in poisoning • • Less Filtration
3 Pharmacology Volume of Distribution (Vd)Q Amount given Plasma concentration Vd = • • Volume of Distribution (Vd) ∝ Amount of Drug in Tissues More Vd → More distribution Loading Dose [LD] Initial high dose given to start the action LD = Vd x Target Plasma Concentration Maintenance DoseQ Repeateddosesgiventomaintaintheplasmaconcentration. MD = CL x Target PC 3. Metabolism Aim of Metabolism → To Make a Drug Water Soluble (Polar) PHASE I REACTIONSQ PHASE II REACTIONSQ Mostly catabolic Reactions Includes • • Oxidation (MC) • • Reduction • • Hydrolysis • • Cyclization • • Deamination Mostly anabolic reactions Includes • • Glucuronidation (MC) • • Glutathione conjugation • • Acetylation • • Methylation • • Sulfate conjugation Purpose of Phase I → Expose the Functional Group on the drug Purpose of Phase II → Makes the drug water soluble Enzymes • • Divided into Microsomal and Non-microsomal Microsomal Non-microsomal Present in smooth endoplasmic reticulum Present outside SER Can be induced or inhibited Cannot be induced or inhibited Enzyme InducersQ Enzyme inhibitorsQ G -Griseofulvin P -Phenytoin R -Rifampicin S -Smoking Cell -Carbamazepine Phone -Phenobarbitone Vit -Valproate K -Ketoconazole Can’t -Cimetidine Cause -Ciprofloxacin Enzyme -Erythromycin Inhibition -Isoniazid Cytochrome p450 Enzymes These are one type of microsomal enzymes. CYP3A4 CYP2D6 CYP2C19Q C : Cyclosporine T : Tacrolimus S : Statins C : CAT (Cisapride, Astemizole, Terfenadine) A :Amiodarone N :Navirs 2 : b-Blockers D:Anti-Depressants 6:Anti-Anthythmies (except amiodarone) Clopidogrel CYP2C9Q Warfarin Phenytoin Clopidogrel CYP2C19 PPI – Active Therefore, PPIs are avoided with clopidogrel 4. Excretion
Ad
4 Cerebellum Quick Revision Notes Glomerular Filtration • • Lipid soluble as well as water soluble drugs can be filtered • • Filtration is inversely proportional to Plasma Protein binding Tubular Reabsorption • • 99% of GFR is reabsorbed – – Lipid soluble drugs reabsorbed – – Water soluble drugs excreted Tubular Secretion • • Due to pumps/transporters in proximal tubules • • These transporters are Saturable (One drug can be transported at one time) • • Probenecid prolongs action of penicillins by inhibiting tubular secretion Kinetics of Elimination Half Life [t1/2 ] • • It is the time in which plasma concentration of a drug becomes half. • • Half-life is constant in first order kinetics. Question: t1/2= 6hrs, after 1 day • • How much drug remains in body → 6.25% • • How much drug eliminated from body →100-remaining→ 93.75% Importance of t ½: • • Dose cannot be calculated • • Dosing Interval/ Frequency can be known Formula of Half-life: t K 1 2 0 693 = . (where, K is elimination rate constant) As So, K CL Vd = t X Vd CL 1 2 0 693 = . Order of Kinetics First order kinetics Zero order kineticsQ → Fraction is constant → Amount is constant R a PC CL = Constant t½ = Constant R = Constant CL a 1/ PC t½ a PC • • Majority of drugs follow First Order Kinetics Drugs Following Zero Order Kinetics areQ Zero → Zero order Kinetics W → Warfarin A → Alcohol/Aspirin T → Theophylline T → Tolbutamide Power → Phenytoin PHARMACODYNAMICS: It deals with action of a drug as well as the mechanism of action Major mechanism of action of a drug are through enzymes or through receptors. Enzyme inhibitionQ Km Vmax Competitive ↑ - Non competitive - ↓ Lineweaver Burke Plot: • • Also known as double reciprocal plot • • Graph between 1/S (on X-axis) and 1/V (on Y-axis)
5 Pharmacology • • X-axis tells Km and Y-axis tells Vmax • • If lines intersect at X-axis, it is non-competitive inhibition • • If lines intersect at Y-axis, it is competitive inhibition Classification of DrugsQ Drug Intrinsic Activity Agonist Maximum [+1] Partial Agonist Submaximum [0 to 1] Inverse Agonist Opposite action [-ve] Antagonist No action of itself but interfere with action of other drugs [0] Classification of Receptors 1. lonotropic Receptors • • The receptors present on ion channels are known as ionotropic receptors. • • Fastest acting receptors 2. Enzymatic Receptors • • These are present on cell membrane with intracellular and extracellular ends. • • Drug binds outside and enzyme is activated inside and action is produced • • Aka Tyrosine Kinase Receptors 3. G-Protein Coupled Receptors [GPCR] Works by one out of the 3 mechanisms • • By changing the level of cAMP • • Can act through Ca2+ • • Can open the ion channels
Ad
6 Cerebellum Quick Revision Notes Types of G proteins Type Mechanism Second/Third messenger GS Stimulate adenylate cyclase ↑ cAMP Gi Inhibit adenylate cyclase ↓ cAMP Gq Convert PIP2 to IP3 and DAG IP3 DAG Calcium 4. Intracellular Receptors A. Cytoplasmic Receptors B. Nuclear Receptors • • Only Lipid soluble drugs acts through these receptors • • Thus, whether a drug binds the cytoplasmic receptors or the nuclear receptors, it will finally work through DNA (nuclear mechanism) • • These are also called nuclear recetor superfamilty • • These are slowest acting receptors. Receptors Examples 1. Ionotropic GABAA , NMDA, NN , NM , 5HT3 2. Enzymatic Cytokines, Prolactin, Insulin, GH 3. Intracellular A. Cytoplasmic B. Nuclear Vit D, Glucocorticoids, Mineralocorticoids Vit A, Thyroid hormones, Sex hormones 4. GPCR Most others Log Dose Response Curve (Log DRC) • • S-shaped curve [Sigmoid Curve) • • Clinically more useful than DRC • • 3 important parameters obtained from log DRC: 1. Potency 2. Efficacy 3. Slope Potency • • To produce a similar response if a drug is required in lesser dose, it is more potent • • On log DRC, left-sided curve is more potent drug whereas right-sided curve is less potent Efficacy • • Relates to maximum effect of a drug regardless of dose • • Higher the curve, more is efficacy H - Height tells aboutQ E - Efficacy L - Left side drugs are more P - Potent C → Most efficacious (Highest curve) D → Least efficacious (Lowest curve) D → Most potent (Most left) B → Least potent (Most right)
7 Pharmacology Quantal DRC • • For All or None phenomenon, where grade of response cannot be plotted. • • Percentage of subjects responding are kept on Y-axis • • Tells about effect of a drug in population i) If 50% respond to a particular dose → Then it is called ED50 (Median Effective dose) ii) If 50% of animals die after receiving a particular dose it is median lethal dose (LD50 ). Therapeutic index = LD50 /ED50 Q • • Therapeutic index is margin of the safety of a drug The Drugs and Cosmetics Act – – An act to regulate the import, manufacture, distribution and sales of drugs. • • Spurious drug: Imitation of or substitute of another drug in a manner likely to deceive the name of another drug. The less known pharmaceutical company try to take advantage of reputation of a well-known company. • • Misbranded drug: If a drug is not labelled in prescribed manner or its label contains any statement which makes any false claims for the drug. • • Adulterated drug: If it contains filthy, patrid or decomposed substances. Clinical Trials Testing of drugs in humans is called clinical trials • • Licensing Authority to give approval for a new drug in USA is FDA whereas in India it is DCGI (Drug Controller General of India) Q Q Q Phase Zero Clinical Trials • • Micro-dosing study • • It is conducted on humans • • Maximum amount of drug given is 100 mcg or (1/100)th of Human Equivalent Dose, whichever is lower • • Radiolabeled substances are added with this sub therapeutic dose to know the Pharmacokinetics of the drug. • • It is not mandatory Q
Ad
8 Cerebellum Quick Revision Notes Pregnancy Categories: Drugs are categorized into 5 groups according to safety in pregnancy Category Special points A Safest in pregnancy B C D X Contra-indicated in pregnancy e.g. ThalidomideQ Note: • • Schedule X drugs and category X drugs are totally different. • • Schedule X include narcotic and psychotropic drugs e.g. ketamine. • • Category X contain teratogenic drugs like thalidomide • • Schedule H drugs require prescription of a RMP. SAFE AND UNSAFE DRUGS IN PREGNANCY Condition Drugs safe in Pregnancy Drugs to beQ avoided in Pregnancy Hypertension Labetalol, Methyldopa ACE Inhibitors and ARBs Anti-coagulants Heparin Warfarin Bipolar disorders Anti-psychotics Valproate (Contra- indicated) Lithium (Avoid) Anti-thyroid Propylthiouracil Carbimazole (1st trimester) Anti-microbials Penicillins, Cephalosporins Macrolides Tetracyclines Quinolones Aminoglycosides Anti-Epileptics Levetiracetam Lamotrigine Valproate Enteric Coating of Drugs: • • This is a coating that dissolves in alkaline medium only. • • It can be used for – – Protecting the acid labile drugs from gastric acid, e.g., proton pump inhibitors. – – It can protect gastric mucosa from irritant drugs e.g. NSAIDS – – It increases the absorption of drugs that are preferentially absorbed distal to stomach. Fixed Dose Combinations (FDC): When two or more drugs are combined to- gether in a particular ratio. Advantages: • • Compliance improves • • One drug may reduce the adverse effects of the other drug • • Efficacy may increase • • Cost may decrease Disadvantages: • • May be used irrationally. • • If adverse effect occurs, it cannot be ascribed to one drug. • • Drugs with different pharmacokinetics cannot be combined. • • Dose of one drug cannot be altered independently as per requirement. Prescription Writing Prescription is the written order by the doctor to the pharmacist to dispense some medication.Q Note: • • Without date and signature (initials), the prescription is invalid. • • Drug name should never be written in short form (e.g., write paracetamol, not PCM) • • Abbreviations like OD, BD, HS should not be usedQ • • In dose of drug – – Leading zeros should always be mentioned (e.g., 0.5 mg is correct but .5 mg is wrong) – – Trial zeros should never be mentioned (e.g., 5 mg is correct but 5.0 mg is wrong) – – Microgram should be written as mcg not μg.Q
9 Pharmacology Q8. Which of the following drugs follow zero order kinetics? A. Phenytoin B. Diclofenac C. Morphine D. Propranolol Q9. Identify the type of inhibition from the given graph A. Competitive B. Non-competitive C. Un-competitive D. Allosteric Q10. True about non-competitive inhibition is A. Km remains same, Vmax decreases B. Km increases, Vmax remains same C. Km decreases, Vmax increases D. Km increases, Vmax increases Q11. Identify the missing substance X marked in the box in the given diagram A. G protein B. Protein C C. Cyclic AMP D. Calcium Previous Years Questions Q1. Which of the following factor in PC vs time graph is a measure of extent of drug absorption of a drug? A. Area under the curve B. Half life C. Cmax D. Tmax Q2. Rate of administration of a drug is equal to rate of elimination. How will you calculate the dosing rate of the drug to maintain steady state concentration? A. Dosing rate = Vd x target plasma concentration B. Dosing rate = CL x target plasma concentration C. Dosing rate = Vd/target plasma concentration D. Dosing rate = CL/target plasma concentration Q3. Anionic and slightly acidic drugs usually bind to A. Albumin B. Alpha acid glycoprotein C. Ceruloplasmin D. Globulin Q4. High plasma protein binding of a drug results in: A. Decreased glomerular filtration B. High volume of distribution C. Lowers duration of action D. Less drug interaction Q5. A patient with stroke was started on clopidogrel. He developed another episode of stroke 6 months later. Which of the following is the likely cause? A. Rapid metabolism by CYP 1A2 B. Poor metabolism by CYP 2C19 C. Poor metabolism by CYP 2D6 D. Poor metabolism by CYP 2E1 Q6. Which of the following treatment option is utilized in salicylate poisoning? A. Alkalinization of urine B. Acidificaition of urine C. Alkalinization of blood D. Acidification of blood Q7. Elimination rate constant of a drug is 0.05/hr. What is its half life? A. 6.5 hr B. 20 hr C. 13.9 hr D. 8 hr Answers 1. - A 2. - B 3. - A 4. - A 5. - B 6. - A 7. - C 8. - A 9. - A 10. - A 11. - C
Ad
10 Cerebellum Quick Revision Notes Q12. Which of the following statement is correct regarding the given graph? A. Drug A is agonist and Drug B represents inverse agonist B. Drug C represents agonist and Drug D is inverse agonist C. Drug A is agonist and Drug D is inverse agonist D. Drug B is partial agonist and Drug C is inverse agonist Q13.TypeofstimulatoryGproteininPIP2-Phospholipase activation pathway is A. Gs B. Gi C. Gq D. Go Q14. Drug acting via tyrosine kinase receptor is A. TRH B. TSH C. Insulin D. MSH Q15. Which of the following drugs act through intracellular receptors? A. Thyroxin B. Glucagon C. Epinephrine D. Parathyroid hormone Q16. Find therapeutic index of a drug from the information given below in the graph A. 1 B. 2 C. 4 D. 8 Q17. What does LD50 signifies A. It is the dose at which 50% of animals will die B. It is the dose at which 50 animals will die C. It is the dose at which 50% patients will get the desired response D. It is drug that will be effective at 50% dose Q18. Which of the following statements about these drugs is true? A. Drug A is most potent B. Drug A and B have equal efficacy but B is more potent than drug A C. Drug C is least potent D. Drug B has more potency but less efficacy than drug A Q19. Which of the following statement is correct about clinical trials? A. New drug application is filed with Phase 2 clinical trials B. Phase 0 clinical trials is for checking the pharma- cokinetics of the drug C. In Phase 3, open label studies are done D. Phase 2 is post marketing surveillance. Answers 12. - C 13. - C 14. - C 15. - A 16. - C 17. - A 18. - A 19. - B
11 Pharmacology Q20. New drug application is filed after which phase of clinical trials? A. Phase 1 B. Phase 2 C. Phase 3 D. Phase 4 Q21. Manufacturer of a drug company labels the drug contains 500 mg paracetamol. On quantitative analysis by the authorities, it was found to contain only 200 mg of drug. According to drugs and cosmetics act 1940, this type of drug is known as? A. Spurious drug B. Adulterant drug C. Unethical drug D. Misbranded drug Q22. Identify the true statement regarding Clinical Trials: A. Phase 1 is done to determine efficacy in patients B. Healthy volunteers are recruited for the first time in Phase II C. Randomized Controlled Trials in patients is done in Phase III D. Phase IV is Pharmacokinetics study in animals Q23. All of the following are advantages of enteric coated tablets except A. It increases the half-life of the drug B. It protects acid labile drugs from gastric pH C. It increases the absorption of drugs that are preferentially absorbed distal to stomach. D. It protects stomach from irritant drugs Q24. Category A, B, C, D, X division of drugs is based on A. Safety in pregnancy B. Dose adjustment in renal failure C. Therapeutic index and safety D. Over the counter use of drug Q25. Variation in drug responsiveness to a particular dose of the drug in different individuals can be obtained from: A. Graded Dose Response Curve B. Efficacy C. Potency D. Quantal Dose Response Curve Q26. Which of the following statement is true regarding Fixed Dose Combination of drugs? A. Adverse effect of one drug may be reduced by the other drug B. Two drugs with different pharmacokinetics can be combined easily C. Dose of one drug can be altered independently as per requirement D. Adverse effect can be ascribed to a single drug Q27. Which of the following drug must be sold by retail only production of a prescription by a registered medical practitioner? A. Schedule H B. Schedule G C. Schedule X D. Schedule M Q28. As an Indian medical intern, which of the following is the correct format for prescription of alprazolam? A. Tablet alprazolam 0.5 mg once a day before bed time for 7 days B. Tablet alprazolam 0.5 mg HS for 7 days C. Tablet alprazolam 500 mcg one tablet OD for 7 days D. Tablet alprazolam ½ mg tablet HS daily Answers 20. - C 21. - D 22. - C 23. - A 24. - A 25. - D 26. - A 27. - A 28. - A
Ad
Location Neurotrans- mitter Preganglionic parasympathetic Preganglionic sympathetic Postganglionic parasympathetic Postganglionic sympathetic • • At all places • • At sweat glands ACh ACh ACh NA ACh Actions: Location Parasympathetic Sympathetic Heart Bronchus GIT Bladder Glands Pupil Sexual system ↓↓ Bronchoconstriction Diarrhea Contract ↑ Secretions Miosis Erection + + + Bronchodilation Constipation Relax ↓ Secretions Mydriasis Ejaculation PARASYMPATHETIC SYSTEM Major neurotransmitter is ACh It works on cholinergic receptors Cholinergic Receptors Nicotinic Receptor Muscarinic Receptor NN → Ganglia NM → NMJ (require optimal stimulation) M1 → Stomach: ↑HCl M2 → Heart: ↓ HR, ↓ Conduction M3 → Bronchus : BC GIT : ↑ Peristalsis Bladder : ↑ Contraction Glands : ↑ Secretions Pupil : Miosis Chapter - 2 Autonomic Nervous System Origin: Neurotransmitters:
13 Pharmacology CHOLINERGIC DRUGS: Drugs stimulating the parasympathetic system can be: Directly Acting Cholinergic Drugs: DRUG ACTS ON ACTION INDICATION Pilocarpine Pupil [M3] Miosis Angle closure glaucoma Q Indirectly Acting Cholinergic Drugs: • • These drugs act by inhibiting AChE. • • These may be reversible or irreversible AChE inhibitors. • • Reversible AChE inhibitors are used clinically whereas irreversible AChE inhibitors are toxic. Reversible AChE Inhibitors: Uses of NeostigmineQ Irreversible AChE Inhibitors Include Organophosphates - Malathion Parathion Carbamates - Carbaryl Propoxur Organophosphate Poisoning: Clinical features: Receptor stimulated Feature M1 Aciditiy M2 Bradycardia and Hypotension M3 • • Pin point pupil • • ↑ Secretions • • Diarrhea • • Urination • • Bronchoconstriction M1, M2, M3 Coma NM Muscle weakness NN Tachycardia and Hypertension Note: • • Nicotinic symptoms (NN ) are extremely rare. • • If pin point pupil with increase in secretions are present, diagnosis of OP poisoning is almost sure. Treatment 1. AtropineQ • • DOC For OP and Carbamate poisoning • • Given by iv route (every 5 min) till signs of atropinization occur. • • Atropine cannot reverse muscle weakness Signs of Atropinization • • ↓ Secretions → Most reliable (Most specific) sign • • Mydriasis → Most commonly used sign • • Tachycardia → HR > 100 bpm Note: Atropine is not used in organochlorine (endrin) poisoning. 2. AChE Reactivators (Oximes)Q Pralidoxime [PAM] Di Acetyl Monoxime [DAM] • • Not DOC • • Only effective in OP Poisoning • • PAM acts only peripherally, DAM has both central as well as peripheral actions.
Ad
14 Cerebellum Quick Revision Notes ANTICHOLINERGIC DRUGS Organ Receptor blocked Drugs Uses Stomach M1 Pirenzepine Telenzepine Peptic ulcer Heart M2 Atropine (DOC) Bradycardia AV block Bronchus M3 Ipratropium Tiotropium Bronchial asthma COPD Bladder M3 S- Solefenacin O- Oxybutynin F- Flavoxate T - Tolterodine BladDAR- DARifenacin Overactive bladderQ EYE M3 Atropine Homatropine Cyclopentolate Tropicamide Longest acting: Atropine Shortest acting: Tropicamide Fundoscopy Refraction testing Iridocyclitis DOC in children–Atropine eye ointment ATROPINE POISONING: (ANTICHOLINERGIC POISONING) • • Patient has a history of taking some wild fruit (Dhatura/Belladona) and presents withQ D – Dry mouth, Delirium H – Hyperthermia A – Agitation T – Tachycardia U – Urinary R – Retention A – Accommodation lost (Blurred vision, Photophobia) • • DOC for treatment of atropine poisoning is physostigmine.Q SYMPATHETIC NERVOUS SYSTEM • • Major neurotransmitter is nor-adrenaline Adrenergic Receptors a1 a2 Location Action Presynaptic receptor → Acts like brake to sympathetic system Blood vessels Vasoconstriction Eye Mydriasis Prostatic urethra ↓ Outflow
15 Pharmacology b1 b2 b3 Location Action Location Action Location Action Heart ↑ HR, BP Lungs Bronchodilation Fat Lipolysis JG cells Renin secretion GIT Constipation Bladder Relax Bladder ↓ Out flow Glands ↓ Secretions Uterus Tocolytic Blood vessels Vasodilation Skeletal muscle spindle Tremors Liver ↑ Blood sugar Effect on blood vessels A1 -> C α1 – Cause vasoconstrictionQ B2 -> D β2 – Cause vasodilation Effect on metabolism: • • Sympathetic system protects from hypoglycemia by two mechanisms: Warning symptoms Hypoglycemia reversal • • Tachycardia (b1 ) • • Palpitations (b1 ) • • Tremor (b2 ) • • Sweating (M3 ) • • By changing metabolism (b2 ) - ⊕ Gluconeogenesis - ⊕ Glycogenolysis - ⊝ Glycogenesis • • Beta Blockers cause (in diabetic patients) 1. Masking of warning symptoms 2.Prevent reversal of hypoglycemia • • So, b blockers are contraindicated in diabetic patients. • • Sweating is only reliable symptom of hypoglycemia in diabetics on b blocker medication.Q ADRENERGIC DRUGS: These can be divided into: • • Indirectly Acting Drugs • • Directly Acting Drugs Indirectly Acting Drugs COCAINE - It acts by inhibiting reuptake of NAQ • • It is a local anaesthetic – – All LA cause vasodilation except cocaine – – Cocaine cause vasoconstriction and hypertension • • It is an addictive drug – – Shows tactile hallucinations (cocaine bugs): Scratching of skin – – Cause palatine perforation – – Overdose characterized by ƒ ƒ Agitation ƒ ƒ Ulcers or scratch marks on skin ƒ ƒ Sympathetic symptoms (Tachycardia, Mydriasis, Hypertension, MI) Note: Cocaine does not cause bradycardia since it is a sympathetic drug. Directly Acting Drugs 1.CATECHOLAMINES – Not effective orally Endogenous Exogenous Adrenaline (a1, a2, b1, b2) NA (a1, a2, b1) Dopamine (D1, b1, a1) Dobutamine (b1) Isoprenaline (b1, b2) Fenoldopam (D1) Uses of Catecholamines Adrenaline 1. Anaphylactic Shock • • DOC is Adrenaline • • Route of choice is I.M. or S.C. • • Concentration is 1:1000 (0.5 ml)Q 2. Cardiac Arrest • • CPR is done first • • Adrenaline is useful • • Concentration is 1:10,000Q • • Preferred routes are IV > Intraoseous > ET
Ad
16 Cerebellum Quick Revision Notes Nor-Adrenaline • • DOC for septic shock • • Effect is monitored by checking mean blood pressure Dopamine Acts onQ Receptors Dose (mcg/ kg/min) Organ Action D1 < 2 Blood vessels Vasodilation (Max in Renal BV) b1 2-10 Heart Stimulation a1 > 10 Blood vessels Vasoconstriction Uses 1. CHF 2. Shock + Oliguria [DOC] Dobutamine • • Mainly b1 agonist • • Used for CHF Fenoldopam • • Only D1 agonist • • Used for hypertensive emergencies Isoprenaline • • ↑ SBP but ↓ DBPQ • • Maximum increase in pulse pressure 2. NON-CATECHOLAMINES Stimulates Drugs Action a1 Phenylephrine eye drops Mydriasis without cycloplegia Methoxamine Mephentermine → Vasoconstriction → Used in shock Xylometazoline Oxymetazoline Naphozoline → Nasal decongestants a2 Clonidine Methyldopa →Brakeforsympatheticsystem →Usedforhypertension b2 Salbutamol Terbutaline Salmeterol Formoterol → Bronchodilation → Used for asthma by inhalational route Ritodrine Isoxsuprine → Tocolytic → Used for preterm labour b3 Mirabegron Overactive bladder Note: Beta-2 agonists can cause following adverse effects: – – T - Tremors – – T - Trachycardia – – T - T-wave changes in ECG (due to hypokalemia) – – Pulmonary edema - by ritodrine – – However, b2 agonists do not cause hypoglycemia.Q ANTI - ADRENERGIC DRUGS These may be alpha blockers or b - Blockers. ALPHA BLOCKERS These can be non-selective (α1 + α2 ) blockers or selective α1 blockers Non-selective α blocker α1 Blocker 1. Used in severe hypertension 2. Can cause severe tachycardia 1. Used in mild to moderate hypertension 2. Cannot cause severe tachycardia Non-Selective α Blockers Irreversible Reversible Phenoxybenzamine Phentolamine, Tolazoline Used for – Pheochromocytoma Used for – Cheese Reaction – Clonidine withdrawal Selective α1 Blockers • • Prazosin • • Terazosin • • Doxazosin • • Alfuzosin Uses • • BPH (Due to a1A blockade) • • Scorpion sting (D.O.C is Prazosin) Adverse Effect First Dose (Postural) Hypotension → a1 blockers always started at bed-time.Q Types of α1 receptors α1A α1B/1D On Prostatic Urethra On Blood Vessels TAMSULOSIN SILODOSIN • • No postural hypotension • • DOC for normotensives with BPH
17 Pharmacology Benign Prostatic Hyperplasia: (BPH) α1A blockers • • Tamsulosin - Stops the dynamic component and do not affect the size of prostate i.e they are only for the symptoms of BPH but do not stop the growth of prostate. 5-α reductase inhibitors: • • Finasteride - Stops the conversion of Testosterone to DHT which control/stops the growth of Prostate in BPH (Static Component). 2. BETA (β) BLOCKERS Beta-1 + Beta-2 # (First Generation) Beta-1 # (Second Generation) Cardiac and non-cardiac uses Contraindicated in Asthma, DM and PVD Only cardiac uses Relatively safe 1. Beta-1# or Cardio-Selective or 2nd Generation Beta # New → Nebivolol Beta → Betaxolol Blockers → Bisoprolol Act → Acebutolol Exclusively → Esmolol At → Atenolol Myo → Metoprolol Cardium → Celiprolol → These are relatively safe in Asthma, PVD & DM 2. Intrinsic Sympathomimetic Activity [ISA] or Partial Agonists → Less chances of causing severe bradycardiaQ Contain → Celiprolol Partial → Pindolol Agonist → Alprenolol Activity → Acebutolol Indications Cardiac Uses 1. Hypertension 2. Classical Angina [C/I in Variant angina] 3. MI 4. Chronic CHF [C/I in acute CHF] 5. Arrhythmia Non-Cardiac Uses Play - Performance anxiety (DOC : Propranolol) The – Thyrotoxicosis (DOC : Propranolol) G – Glaucoma (Timolol is used) A – Akathisia (DOC : Propranolol) M – Migraine prophylaxis (DOC : Propranolol) E – Essential tremors (DOC : Propranolol) Adverse Effects and Contra-indications Due to β1 Blockade 1. ↓ Rate →Bradycardia(C/IinSicksinussyndrome) 2. ↓ Conduction → AV Block 3. ↓ Contractility → Acute CHF Due to β2 Blockade 1. Asthma 2. Peripheral vascular Disease 3. Diabetes mellitus 4. Variant angina. GLAUCOMA → Glaucoma is characterized by ↑ IOP: It may be due to – – ↑ Aqueous humor production – – ↓ Aqueous humor drainage
Ad
18 Cerebellum Quick Revision Notes DRUG OF CHOICE - POAG – Latanoprost - Angle closure glaucoma – Acetazolamide - Acute congestive glaucoma – Mannitol Adverse Effects MiotiCS – – Cataract – – Stenosis of NLD PGF2a Analogues (Latanoprost)Q – – Pigmentation of Iris (Heterochromia Iridis) – – Growth of eyelashes (Hypertrichosis) – – Fluid in macula (Macular edema) – – Contra-indicated in uveitis ApracLonIDine Q – – Lid retraction Brimonidine Q – – Causes Brain suppression in Infants (Leads to Apnea) – – C/l in children < 2yrs Netarsudil (Rho-kinase inhibitor)Q – – Cornea verticillata. ANS PRACTICALS 1. Ileum graphQ
19 Pharmacology 2. Dog Blood Pressure ExperimentQ A: Adrenaline B: Nor-adrenaline C: Isoprenaline Biphasic Response → Effect of high dose of adrenaline → Dog is given Phentolamine → α-blocker → BP → → Then, Epinephrine (high dose) is given → BP ↓ →No Biphasic Response produced → Called Vasomotor Reversal of Dale → Dog is given Atropine first → HR ↑ → After this, a high dose of ACh given → BP & HR ↑ → Nicotinic action appear → Stimulate sympathetic ganglia → Ephedrine given → BP ↑ → Same dose is repeated → Less ↑ in BP → Called Tachyphylaxis
Ad
20 Cerebellum Quick Revision Notes Previous Years Questions Q1. Which of the following action is expected on stimulation of muscarinic receptors? A. Erection B. Ejaculation C. Increased contraction of cardiac muscles D. Bronchodilation Q2. A farmer presented with pin point pupil and increase in secretions. Likely poisoning is A. Organophosphate poisoning B. Dhatura poisoning C. Opioid poisoning D. Atropine poisoning Q3. Topical antiglaucoma drug dorzolamide act by which of the following mechanism of action? A. Carbonic anhydrase inhibition B. Beta blockade C. Alpha agonist D. Prostaglandin analog Q4. A patient with history of snake bite presented in emergency with symptoms of fatigue and irritability. Ten vials of antivenom were administered intravenously but the patient is still having difficulty in swallowing, ptosis and respiratory distress. What should be the next line of management? A. Atropine and neostigmine B. Nebulizer with salbutamol C. IV hydrocortisone D. Antihistamines Q5. A patient on treatment of myasthenia gravis presents with increasing muscle weakness. Which of the following drug is used to differentiate myasthenia gravis from cholinergic crisis? A. Edrophonium B. Pilocarpine C. Atropine D. Pyridostigmine Q6. A 20 year old boy was brought to emergency room after consuming some unknown substance. The patient was sweating profusely, saliva was drooling from mouth and tears were present. The boy had involuntary urination and diarrhea. On examination, the heart rate was 58 beats per minute and blood pressure was 80/60 mm Hg. Which of the following is the drug of choice for treatment of this patient? A. Atropine B. N-acetylcysteine C. Naloxone D. Physostigmine Q7. A study was conducted to see the effect of different drugs on isolated mammalian intestinal tissue in Dale’s organ bath. The following graph is obtained. Which of the following is the likely drug? A. Acetylcholine B. Barium chloride C. Adrenaline D. KCl Q8. An experiment on dog blood pressure was done by adding different drugs. The drugs added and the effects are as shown in the given figure. This experiment is done to demonstrate the Answers 1. - A 2. - A 3. - A 4. - A 5. - A 6. - A 7. - C 8. - B
21 Pharmacology Answers 19. - B 20. - C A. Muscarinic action of ACh B. Nicotinic action of ACh C. Potentiation of ACh D. Antagonistic action of ACh Q9. After eating an unknown plant, A child presented to emergency in comatose state. The pupils were dilated and skin was dry. Body temperature is raised and heart rate is high. These signs and symptoms can occur with the intake of which of the following substance? A. Dhatura B. Poppy seeds C. Mushroom D. Cannabis Q10. Topical atropine is not given in A. Acute congestive glaucoma B. Corneal ulcer C. Malignant glaucoma D. Acute anterior uveitis Q11. All of the following are Side effects of Ritodrine except? A. Hypoglycemia B. Tachycardia C. Hypotension D. Pulmonary edema Q12. Which of the following is the action of dopamine at low doses? A. It increases renal blood flow B. It causes vasoconstriciton C. It has positive chronotropic action D. It causes hypotension Q13. A lady was stung by many bees. She developed breathing difficulty and hypotension. Drug used for treatment of this condition is? A. Adrenaline B. Nor-adrenaline C. Dopamine D. Isoprenaline Q14. A drug addict patient presented with agitation and ulceration on skin. The patient had severe itching and scratch marks on the body. On examination there is presence of tachycardia, mydriasis and hypertension. Likely substance responsible for these symptoms is? A. Cocaine B. Cannabis C. LSD D. Heroin Q15. Which dose of dopamine act preferably on beta-1 receptors? A. Less than 2 mcg/kg/min B. 2-10 mcg/kg/min C. 10-20 mcg/kg/min D. More than 20 mcg/kg/min Q16. A patient was on metoprolol therapy for hypertension. He was also administered verapamil. Which of the following is likely to happen with above combination therapy? A. Torsades de pointes B. Ventricular tachycardia C. Ventricular fibrillation D. Bradycardia with AV block Q17. A 65 years old patient presented with dribbling of urine with urgency. He was started on prazosin therapy but the patient developed postural hypotension. Which of the following is the better alternative drug for this patient? A. Terazosin B. Tamsulosin C. Timolol D. Phenoxybenzamine Q18. Beta blockers are avoided in all of the following conditions except A. Glaucoma B. Peripheral vascular disease C. Diabetes mellitus D. COPD Q19. Hypertension and pulmonary edema associated with scorpion sting is managed by: A. Carvedilol B. Prazosin C. Spironolactone D. Phentolamine Q20. Which of the following is a contraindication to the use of Beta Blockers? A. Glaucoma B. Tachycardia C. Bronchial asthma D. Hypertension 9. - A 10. - A 17. - B 18. - A 11. - A 12. - A 13. - A 14. - A 15. - B 16. - D
Ad
22 Cerebellum Quick Revision Notes Q21. A known patient of bronchial asthma was started on treatment with an anti-glaucoma drug. During the course of treatment, asthma worsened. Which drug is likely responsible for these symptoms? A. Timolol B. Brimonidine C. Latanoprost D. Pilocarpine Q22. A patient had symptoms of redness and photophobia. On examination, cells were present in anterior chamber with keratic precipitates. Intraocular pressure was measured to be 38 mm Hg. Which of the following anti-glaucoma drug should be avoided? A. PG analogues B. Beta blockers C. Mannitol D. Carbonic anhydrase inhibitors Q23. Drug capable of causing ocular hypotension with apnoea in infants is: A. Acetazolamide B. Latanoprost C. Brimonidine D. Apraclonidine Q24. Anti-glaucoma drug that acts by increasing uveoscleral outflow is A. Latanoprost B. Timolol C. Pilocarpine D. Dorzolamide Q25. A patient with bronchial asthma presents with raised intraocular pressure. Treatment of open angle glaucoma in this patient is A. Latanoprost B. Alprostadil C. Gemeprost D. Carboprost Q26. Which anti-glaucoma drug acts by increasing trabecular outflow? A. Netarsudil B. Timolol C. Acetazolamide D. Brimonidine Answers 21. - A 22. - A 23. - C 24. - A 25. - A 26. - A
Chapter - 3 Autacoids - Have autocrine effects [Local effects] - Based on chemical Structure Peptide Autacoids → Angiotensin → Bradykinin Amine Autacoids →Histamine → 5-HT Lipid Autacoids →Prostaglandins →Leukotrienes →Thromboxane HISTAMINE Receptors Location Action Blockers H1 CNS Bronchus Allergy Stimulates RAS Promote wakefulness First and second Generation Drugs H2 Stomach Secrete Acid Ranitidine Cimetidine H3 PreSynaptic BRAKE H3 Inverse Agonist Tiprolisant [Pitolisant] Used for Narcolepsy H4 WBC Chemotaxis H1 Blockers 1st Generation 2nd Generation Cross BBB, cause sedation Do not cross BBB, no sedation Have Anti-cholinergic action → Anticholinergic S/E occur No Anti-cholinergic action Useful for allergy and Possess : Prophylaxis of motion sickness Anti : Akathisia Cholinergic : Common Cold Property : Parkinsonism (Drug induced) Useful only for allergy Promethazine FexofenadineQ • • Terfenadine metabolite Loratidine Cetirizine 5-HT (SEROTONIN) Serotonin Receptors Location Action Drugs Example Uses 5HT1A Presynaptic Brake Agonist BuspironeQ Anxiety 5HT1B/ID BV of Brain Vasoconstriction Agonist Sumatriptan Naratriptan Eletriptan Rizatriptan DOC for Acute Severe Migraine 5HT2A/2C Brain Blockers Clozapine , Olanzapine Atypical Antipsychotics 5HT3 CTZ Emesis Blockers Ondansetron Granisetron Tropisetron Dolasetron PalonosetronQ DOC for vomiting due to Chemotherapy Radiotherapy Post-operativeQ 5HT4 GIT Prokinetic Agonist Cisapride , Mosapride, Prucalopride As prokinetics for GERD
Ad
24 Cerebellum Quick Revision Notes MIGRAINE:Q → Drug of choice for mild to moderate headache – NSAIDs (Paracetamol, Diclofenac) → Drug of choice for Acute severe attack – Triptans → Other drug for Acute severe migraine – Ergotamine → DOC for prophylaxis of migraine – Propranolol New Drugs for Migraine: 1. Lasmiditan (DITANS) Q • • Stimulates 5HT1F receptor and decreases CGRP release. • • This prevents the vasodilation and neuronal inflammation. • • Effective orally. • • It is recently approved for acute attacks of migraine. • • Advantage over triptans is that it does not induce peripheral vasoconstriction. 2. Monoclonal Antibodies Against CGRP • • Approved for prophylaxis of migraine. • • Given by injectable route. – – Erenumab – – Fremanezumab – – Galcanezumab – – Eptinezumab 3. CGRP Antagonist: (GEPANTS) Q • • Used for acute attack • • Effective orally • • Drugs are – – Olcegepant – – Rimegepant – – Ubrogepant PROSTAGLANDINS 1. General Effects • • Fever • • Pain • • Inflammation 2. Platelets • • TXA2 → Aggregation • • PGl2 → Inhibition of aggregation 3. Heart • • Ductus Arteriosus is kept open by PGE1 • • PDA [Patent ductus Arteriosus] is treated by NSAIDs like – – Aspirin – – Indomethacin – – Ibuprofen (DOC) 4. Uterus • • PGs Contract upper segment of uterus • • Used for abortion (Misoprostol is used) 5. Stomach • • PGE2 protect the stomach from peptic ulcer disease • • For NSAID Induced Peptic Ulcer Disease – – Most specific drug is MisoprostolQ – – DOC is proton pump inhibitors 6. Eye PGF2α → ↑ Uveo scleral outflow → Latanoprost → DOC for Primary Open Angle GlaucomaQ
25 Pharmacology NON-STEROIDAL ANTI- INFLAMMATORY DRUGS (NSAIDs) COX 1 COX-2 Constitutive Enzyme Present normally at most places Inducible enzyme Present normally in • • Kidney • • Endothelium • • CNS NSAIDS act by inhibiting COX. These may be: Non-Selective COX Inhibitors Selective COX-2 Inhibitors ↑ Risk of PUD Less risk of PUD Non-Selective COX Inhibitors Drugs - Aspirin : Irreversible COX inhibitor (Antiplatelet), ↑Uric acid - Paracetamol : COX - 3 inhibitor, safe in CKD - Ibuprofen : DOC for PDA - Diclofenac : Partial COX-2 selective - Indomethacin: Sedation is adverse effect - Piroxicam : Longest acting NSAID - Nimesulide : Not used in children (hepatotoxic) - Ketorolac : Given IV Selective COX 2 Inhibitors Drugs - Celecoxib - Rofecoxib - Valdecoxib - Parecoxib - Lumiracoxib • • These have lesser risk of causing PUD • • These increase the risk of MI and stroke - Etoricoxib Longest acting - Rofecoxib and Valdecoxib Withdrawn because of MI and stroke - Parecoxib is given by Parenteral route - Lumiracoxib is withdrawn Due to Liver toxicity GOUT It is characterized by increase in serum uric acid. Acute Gout 1. DOC : NSAIDs (except aspirin and paracetamol) 2. Steriods : If NSAIDs do not work 3. Colchicine (Most effective drug):Q - Can cause myopathy and diarrhea - Inhibit granulocyte migration Chronic Gout Three types of drugs can be used in chronic gout. – Drugs decreasing production of uric acid – Drugs increasing excretion of uric acid (Uricosuric agents) – Drugs increasing metabolism of uric acid Proteins / Purines Xanthine Uric acid Excretion 1 2 3 Allantoin Uricase In birds Xanthine oxidase
Ad
26 Cerebellum Quick Revision Notes 1. ↓ Formation 2. ↑ Excretion AllopurinolQ • • Inhibit xanthine oxidase • • DOC for chronic gout Febuxostat • • Inhibit xanthine oxidase Probenecid Sulfinpyrazone Lesinurad → Plenty of fluids should be taken 3.↑ Metabolism Rasburicase → Recombinant uricase Pegloticase → Long acting uricase These are fastest urate lowering agents for tumor lysis syndromeQ RHEUMATOID ARTHRITIS NSAIDs and Steroids DMARDs or SAARDs • • ↓ Pain and lnflammation • • No effect on disease Progression • • Fast acting • • Slow down the disease progression • • Slow acting 1. Conventional DMARD: Cute and Chloroquine DMARD of choice in pregnancy p Penicillamine Used for Cu poisoning/ Wilson’s disease A Azathioprine G Gold salts L Leflunomide Fastest acting DMARDQ I Inhibitors of JAK Tofacitinib Baricitinib Malika Methotrexate DOC, Needs LFT Monitoring Sherawat Sulfasalazine DOC for ulcerative colitis 2. Biological DMARDs: i. Drugs Inhibiting TNF-a:Q - All are injectable A Adalimumab C Certolizumab E Etanercept Inhibitor lnfliximab Goli Golimumab → ↑ Risk of infections. → Contra-indicated in T.B. and Hepatitis B → Apart from R.A., these drugs can be used for Crohn’s disease as well as Psoriasis ii. IL - 1 Receptor Antagonist:Q ANAKINRA – – A - 1st letter – – KIN - Interleukin – – R - Receptor – – A - Antagonist iii. IL - 6 Receptor Antagonists:Q Tocilizumab → 1st IL- 6 targeted monoclonal Antibody. → Approved for treatment of cytokine release syndrome also. Sarilumab → Used for rheumatoid arthritis S - Six AR - R.A. MAB - Monoclonal antibody iv. Co-stimulation InhibitorsQ • • Abatacept • • Inhibit the interaction of T-cell and Antigen Presenting Cells (APC).
27 Pharmacology Previous Years Questions Q1. Most specific antiemetic for Chemotherapy induced vomiting is: A. Doxylamine B. Tegaserod C. Granisetron D. Domperidone Q2. Buspirone is a drug used in chronic anxiety. It produce its action by acting on which of the following receptors? A. 5HT1A B. 5HT1B C. 5HT2 D. 5HT3 Q3. A boy is planning to travel by bus. Which of the following drug can be used to prevent motion sickness in this person? A. Promethazine B. Cetrizine C. Loratidine D. Fexofenadine Q4. Drug of choice for prophylaxis of migraine is A. Propranolol B. Imipramine C. Flutamide D. Flunarizine Q5. A young female presented with left sided severe throbbing headache associated with nausea, vomiting, photophobia and phonophobia. Which of the following drug can provide immediate relief to this patient? A. Propranolol B. Sumatriptan C. Topiramate D. Flunarizine Q6. Drug of choice in paracetamol overdose is A. N-acetylcysteine B. Dopamine C. Hydralazine D. Furosemide Q7. A 34 week pregnant female with polyhydramnios presents with labour pain. She was treated with indomethacin earlier. Which of the following can be likely outcome in the baby if delivery occurs at this time? A. Patent ductus arteriosus B. Premature closure of ductus arteriosus C. Patent ductus venosus D. Premature closure of ductus venosus Q8. A 60 year old female with renal disease was admitted for pyelolithotomy. Post operative analgesic of choice in this patient is? A. Diclofenac B. Indomethacin C. Naproxen D. Acetaminophen Q9. Which of the following is the fastest urate lowering therapy in tumor lysis syndrome to prevent renal damage? A. Allopurinol B. Febuxostat C. Rasburicase D. Furosemide Q10. A female patient presented with pain and redness in great toe. Serum uric acid level is 9.6 mg/dL. Apart from prescribing analgesics for relieving pain, the physician prescribed a drug which can decrease the formation of uric acid. Which of the following enzyme is likely to be inhibited by this drug? A. Xanthine oxidase B. Thymidylate synthase C. Phosphpribosyl transferase D. DHFR Q11. Drug inhibiting granulocyte migration is: A. Montelukast B. Cromoglycate C. Colchicine D. Felbamate Q12. Pegloticase is used for treatment of :- A. Ankylosing spondylosis B. CPPD C. Chronic tophaceous gout D. Refractory Rheumatoid arthritis Answers 1. - C 2. - A 3. - A 4. - A 5. - B 6. - A 7. - B 8. - D 9. - C 10. - A 11. - C 12. - C
Ad
28 Cerebellum Quick Revision Notes Q13. A patient diagnosed with Rheumatoid arthritis was on medications. After 2 years, he developed blurring of vision and was found to have corneal opacity. Which drug is most likely to cause this? A. Sulfasalazine B. Chloroquine C. Methotrexate D. Leflunomide Q14. Tocilizumab is an immunosuppressive drug used for Rheumatoid arthritis. It is a monoclonal antibody against A. IL-6 B. IL-12 C. IL-2 D. IL-3 Q15. A 40 year old male patient presents to hospital with pain in great toe. It was diagnosed to be a case of gout. Which of the following drug increases the excretion of uric acid in urine? A. Colchicine B. Probenecid C. Allopurinol D. Febuxostat Answers 15. - B 13. - B 14. - A
Diuretics → Cause loss of Na+ & H2 O in urine Classification Based On Site of Action 1. OSMOTIC DIURETICS → Includes mannitol Uses: • • Acute Congestive GlaucomaQ • • Cerebral edema Contra-Indications: • • Cerebral hemorrhage • • Pulmonary edema 2. CARBONIC ANHYDRASE INHIBITORS → Acts on Proximal tubule → Include: Acetazolamide – Given orally or IV Brinzolamide Dorzolamide Indications: Glaucoma (Angle closure glaucoma) Mountain Sickness [DOC]Q Given as eye drops 3. LOOP DIURETICS → Act on thick ascending limb of loop of Henle → Inhibit Na+ K+ 2Cl– symporter → Include Furosemide Torsemide Bumetanide → High ceiling diuretics [High efficacy Diuretics]Q → Effectve in renal failure 4. THIAZIDES → Act on early distal tubule → Inhibit Na+ – Cl– symporter Include Thiazides Thiazide-like diuretics Chlorothiazide Methiazide Polythiazide Indapamide Metolazone Uses • • Hypertension (DOC)Q – – Metolazone is effective in renal failure unlike other thiazides • • Recurrent renal calcium stones • • Diabetes insipidus • • Osteoporosis • • Recurrent renal calcium stones S/E of both Thiazides and Loop diuretics ↓ Na+ ↑ Glucose ↓ K+ ↑ Uric Acid ↓ Mg2+ ↑ Lipids ↓ H+ Note: Loop diuretics cause hypocalcemia whereas thiazides leads to hypercalcemia 5. K+ SPARING DIURETICS → Act on collecting ducts (1) Aldosterone Receptor Antagonists – – Spironolactone – – Epleronone Chapter - 4 Diuretics
Ad
30 Cerebellum Quick Revision Notes Previous Years Questions Q1. Which of the following drug is a carbonic anhydrase inhibitor? A. Acetazolamide B. Hydrochlorthiazide C. Furosemide D. Mannitol Q2. A 25 year old male presented to emergency with head trauma due to road traffic accident. In hospital, the patient developed seizures. Emergency CT scan revealed widespread cerebral edema. Which of the following is diuretic of choice for cerebral edema in this patient? A. Mannitol B. Spironolactone C. Furosemide D. Hydrochlorthiazide Q3. A 28 year old male went to Ladakh. He developed shortness of breath. Which of the following drug will you use for the treatment of mountain sickness at high altitude? A. Acetazolamide B. Furosemide C. Epleronone D. Salbutamol Q4. Hydrochlorothiazide works by inhibiting A. Na+ Cl- pump in DCT B. Na+ Cl- pump in PCT C. Na+ K+ 2 Cl- pump in descending limb of loop of Henle D. Na+ K+ 2 Cl- pump in ascending limb of loop of Henle Q5. At a high altitude of 3000m, a person complains of breathlessness. All of the following can be used for management of this person except A. Intravenous digoxin B. Oxygen supplementation C. Immediate descent D. Acetazolamide Q6. Mannitol is used in the management of: A. Congestive Cardiac Failure B. Acute Congestive Glaucoma C. Acute Renal Failure D. Pulmonary edema Q7. A patient of chronic liver cirrhosis presents with ascites. Which of the following is the best diuretic to be used in this patient? A. Eplerenone B. Chlorthiazide C. Furosemide D. Triamterene Q8. Which of the following diuretic acts on the site X shown in the figure? A. Furosemide B. Hydrochlorthizide C. Spironolactone D. Acetazolamide Answers 1. - A 2. - A 3. - A 4. - A 5. - A 6. - B 7. - A 8. - B (2) Epithelial Na+ channel Blockers – – Triamterene – – Amiloride These drugs cause ↓ Na+ & H2 O → Diuresis ↑ K+ → Hyperkalemia ↑ H+ → Metabolic AcidosisQ P → Potassium sparing Diuretics A → Amiloride S → Spironolactone → Cause Gynaecomastia T → Triamterene E → Epleronone → Do not cause Gynaecomastia Uses: - DOC for Conn’s Syndrome - DOC for Edema in Cirrhosis - DOC for Resistant hypertension
Chapter - 5 Cardiovascular System CONGESTIVE HEART FAILURE In low output CHF, heart is not able to pump enough blood. It results in accumulation of fluid in various parts of body. ACUTE (DECOMPENSATED) CHF Aim of treatment of Acute CHF 1. ↓ FLUID → Loop Diuretics 2. ↑ PUMPING → Inotropics A. b1 Agonists • • Dopamine • • Dobutamine • • Nor-adrenaline • • Isoprenaline B. Phosphodiesterase Inhibitors [Inodilators] • • Inamrinone • • Milrinone CHRONIC CHF (COMPENSATED) Aim of Treatment in Chronic CHF 1.↓ Work 2.↓ Fluid 3.↓ LVH [Cardiac Remodeling] 4.Inotropic action Drugs Used In Chronic CHF → 4’D’ are used Diuretics Dilators Decrease LVH Digoxin 1. ↓ Work → Vasodilators Venodilators Arteriolar dilators Veno + Arteriolar Dilators ↓ Preload Nitrates ↓ Afterload Hydralazine ↓ Preload and ↓ Afterload Na Nitroprusside ACE inhibitors Angiotensin receptor blockers 2. ↓ Fluid → Loop Diuretics 3. ↓ LVH [Cardiac Remodeling] It results due to excessive aldosterone → These drugs decrease mortality in CHFQ A. Beta Blockers B. ACE inhibitors C. Angiotensin Receptor Blockers D. Aldosterone Antagonists
Ad
32 Cerebellum Quick Revision Notes 4.  Contractility (Ionotropics) DIGOXIN → Only inotropic drug that can be given Orally MOA in CHF → Inhibit Na+ - K+ pump that ↑ intracellular calcium and thus inotropic action. MOA in Atrial Fibrillation → Vagomimetic effect lead to ↓ AV conductionQ Adverse Effects 1. Nausea, Vomiting [MC] 2. Arrhythmias MC arrhythmia → Ventricular bigeminyQ Most specific → NPAT with AV BlockQ 3. Xanthopsia / Yellow VisionQ 4. Gynaecomastia Drugs Causing Gynaecomastia DI : DIgoxin S : Spironolactone C : Cimetidine K : Ketoconazole O : Oestrogens Factors ↑ Digoxin Toxicity Metabolic Drugs ↑ Ca2+ ↓ K+ ↓ Mg2+ Quinidine Verapamil Amiodarone Thiazides and Clarithromycin Mx of Digitalis ToxicityQ 1. Correct the cause 2.DOC for Digitalis induced arrhythmias → Lignocaine 3.Digibind for Severe poisoning ANGINA PECTORIS Drugs for Angina Pectoris I. Nitrates II. Calcium Channel Blockers III. Beta Blockers IV. Potassium Channel Openers I. Nitrates Mechanism of action: Nitrates ↓ Nitric oxide ↓ Guanylate cyclase ↓ ↑ cGMP ↓ Vasodilation (Veins >> Arteries) → MOA of nitrates in classical angina - ↓ Preload → MOA of nitrates in variant angina → Dilation of coronary arteriesQ Drugs • • Glyceryl Trinitrate / Nitroglycerine [GTN/ NTG] • • Isosorbide Dinitrate [IDN] • • Isosorbide Mononitrate [IMN] • • Penta Erythrital Tetra Nitrate [PETN] • • Amyl Nitrite [AN] Nitrates ↓ NO ↓ ↑ cGMP Degraded ↓ VD ↓ Hypotension Nitrates should not be given with Sildenafil [Risk of Severe hypotension]Q Sildenafil PDE
33 Pharmacology GTN/NTG and IDN • • DOC for acute attack of angina • • Have high 1st pass metabolism • • Sublingual route preferred → IMN has minimum 1st pass metabolism → Longest acting → PETN → Shortest acting → AN → Amyl nitrite is used in cyanide poisoning as an antidote → Tolerance occurs, if nitrates are continuously present in blood → To avoid tolerance, 6-8 hours of Nitrate Free Period should be maintainedQ ll. L-Type Calcium Channel Blockers → DOC for variant angina - CCB like verapamil and diltiazem → Dipines are not used because they can worsen angina due to reflex tachycardiaQ III. Potassium Channel Opener NICORANDIL → NO Releaser + K+ channel openerQ IV. Beta Blockers – – Useful in classical angina (Act by ↓ HR) – – Contra-indicated in variant angina New Drugs for Angina Pectoris 1. Bradycardiac Agent → IvabradineQ Ivabradine inhibit Na+ channel [Funny current] in SA node → S/E → ↓ Visual acuity (Phosphenes) 2. Rho Kinase Inhibitor → FasudilQ 3. Metabolic Modulators → Fatty Acids require more oxygen for same energy production than glucose → Metabolic Modulation → Making heart to utilize glucose instead of fatty acids DrugsQ 1. Trimetazidine 2.Ranolazine → Main mechanism of ranolazine is now assumed to be inhibition of Late Inward Na channels. MYOCARDIAL INFARCTION (MI) Non-STEMI M → Morphine O → Oxygen N → Nitrates A → Aspirin STEMI S → Streptokinase O → Oxygen N → Nitrates A → Aspirin M → Morphine HYPERTENSION 1. First Line Drugs for Hypertension without any compelling Indications are: A – ACE inhibitors and ARBQ B – Beta Blockers (Not considered first line drugs now) C – Calcium channel blockers D – Diuretics ACE Inhibitors • • Name ends with pril C → Cough A → Angioedema P → Prodrugs except captopril & Lisinopril T → Taste alteration [Dysgeusia] O → Orthostatic / Postural hypotension [max with captopril]Q P → C/l in Pregnancy R → C/lin B/L Renal Artery StenosisQ I → C/I in Increased K+ L → Lower the risk of Diabetic Nephropathy ARBs [Angiotensin (AT1) Receptors Blockers] - Name ends with ‘SARTAN‘ - All points about ACE inhibitors apply to ARB also, except that these do not cause cough and angioedema and ARB are not pro-drugs. - Telmisartan is a PPAR-g agonist and can reverse insulin resistanceQ
Ad
34 Cerebellum Quick Revision Notes 2. DOC in special situationsQ Condition DOC HTN in pregnancy Oral Labetalol > Methyldopa HTN Emergency in pregnancy IV Labetalol HTN Thiazides HTN Emergency Nicardipine > Nitroprusside Resistant Hypertension (Resistant to minimum 3 drugs including thiazides) Spironolactone PULMONARY HYPERTENSION Intravenous Vasodilator Testing (on giving IV CCB, pulmonary artery pressure decreases) → If positive, DOC → CCBQ → If negative, DOC → Endothelin antagonistQ DRUGS USED IN PULMONARY HYPERTENSION 1. Calcium channel blockers: DHPs like amlodipine are DOC if IV vasodilator testing is positive (in < 5% cases) 2. Endothelin antagonists: Bosentan, ambrisentan like drugs are DOC for pulmo- nary hypertension 3. PDEI [Phosphodiesterase Inhibitors] → Sildenafil, Tadalafil 4. Prostaglandins PGI2 → lloprost 5. Selexipag → Prostacylin agonist → Can be given orally SELE → Selective XI → Non injectable [Oral] P → PGI2 AG → Agonist ANTI-ARRHYTHMIC DRUGS Vaughan Williams Classification → Based on predominant mechanism of action Class I → Na+ Channel Blockers Class II → b Blockers Class III → K+ channel blockers Class IV → Ca2+ Channel Blockers Class V → Others Class I DrugsQ → Na+ Channel blockers → ↓ Slope of Phase 0 Class Effect on K+ channel Effect on APD QT interval 1a Blocker ↑ ↑QT 1b Opener ↓ ↓QT 1c No effect - No effect Class 1a Drugs Class 1b Drugs Class 1c Drugs Quinidine Procainamide Lignocaine Phenytoin Tocainide Encainide Flecainide Cause QT Prolon- gation Used only for Ven- tricular arrhythmia Class II → Beta BlockersQ → Used in Tachyarrhythmias Class III → K+ Channel Blockers B → Bretylium I → Ibutilide N D → Dofetilide, Dronedarone A → Amiodarone S → Sotalol → Sotalol has both Class III [Major] & class II Actions
35 Pharmacology AMIODARONE → Longest acting [t1/2 → > 3wks] anti arrhythmic drug → MOA 1. Na+ channel Blocker 2. Beta-Blocker (Non-competitive) 3. K+ channel Blocker [Main action] 4. Calcium channel blocker → Adverse effect of amiodaroneQ The Thyroid (hypo/hyper) (40% iodine is present in amiodarone) Periphery of Peripheral neuropathy My Myocardial depression Lung Lung fibrosis Liver Liver toxicity Cornea is Corneal deposits Photosensitive Photosensitivity (Rash on exposure to sun) (Bluish: Blue man syndrome) Class IV → L-Ca2+ Channel Blockers – – Verapamil – – Diltiazem – – DHPs [Not Used] → Used in Tachyarrhythmias →Shouldnotbecombinedwithβblockers[RiskofSevere Bradycardia and AV Block] Class V Digoxin - Used for AF (in patients with CHF) Atropine - DOC for Bradycardia & AV block Adenosine -Shortestactingantiarrhythmicdrug(t1/2 < 10s) - DOC for PSVTQ ANTI-DYSLIPIDEMIC DRUGS 1. Statins MOA 1.Inhibit HMG-COA Reductase (Rate limiting enzyme in cholesterol synthesis)Q 2.Compensatory ↑ of LDL - R 3.Cholesterol is taken from blood 4.↓ Serum cholesterol Examples – – Atorvastatin – – Rosuvastatin [Longest Acting] – – Pravastatin – – Simvastatin Important Points A. Statins have maximum LDL – Cholesterol lowering potential B. Given at late evening/night • • Atorvastatin & Rosuvastatin are long acting, can be given at anytime of the day • • Rosuvastatin is longest acting statin.Q C. Adverse EffectsQ – – Myopathy → Risk further ↑ with Fibrates and enzyme inhibitors like clarithromycin and erythromycin. – – Hepatotoxicity – – Hyperglycemia: ↑ Risk of new onset DM. D. Pleiotropic EffectsQ These are additional benefits apart from improving lipid profile. PL → Plaque Stabilization E → ↓ Endothelial dysfunction I → ↓ Inflammation O → ↓ Oxidative Stress TR→ ↓ Thrombosis Opic
Ad
36 Cerebellum Quick Revision Notes 2. Other Drugs Fibrates Clofibrate Fenofibrate • Max TG lowering potential • S/E → Gall StonesQ Ezetimibe Inhibit absorption of cholesterol from intestine Usually combined with statins BABA Cholestyramine Colestipol DOC in pregnancy and children S/E → ↑ TG Niacin Vitamin B3 Max. HDL - C increasing potential Compliance limiting S/E → Itching & flusing HyperuricemiaQ Hepatotoxicity 3. New Drugs A. PCSK - 9 (Pre Protein ConvertinSubtilisinKexin Type 9) InhibitorsQ • • PCSK-9 binds to LDL - receptors and take it to lysosomes that result in breakdown of LDL receptors. • • Thus PCSK 9 inhibitors prevent breakdown of LDL receptors. When more LDL receptors are present, they can take up more LDL-cholesterol from blood. • • So, we can use these drugs as hypolipidemic drugs. • • Alirocumab and Evolocumab are monoclonal antibodies against PCSK-9 B. MTP (Microsomal Triglyceride Triglyceride Transport Protein) Inhibitors • • Triglycerides are packed in VLDL by MTP • • Drug inhibiting MTP is Lomitapide C. Evinacumab • • Monoclonal antibody against ANGPTL1 (Angiopoietin Like Protein 3) • • It acts independent of LDL-receptor density.
37 Pharmacology Previous Years Questions Q1. A hypertensive patient has grade 4 renal failure and GFR less than 30 mL/min. The physician wants to prescribe a thiazide diuretic. Which is the best drug for this patient? A. Hydrochlorthiazide B. Chlorthalidone C. Metolazone D. Indapamide Q2. A patient with chronic stable angina presents with pedal edema, breathlessness and other symptoms of heart failure. Which of the following drug can increase longevity in this patient? A. Nifedipine B. Digoxin C. Lisinopril D. Torsemide Q3. Drug of choice for treatment of digoxin induced ventricular arrhythmias is? A. Atropine B. Lidocaine C. Amiodarone D. Procainamide Q4. A patient on digoxin therapy accidently consumed 8 tablets of digoxin 0.25 mg. Two hours later, he presented to emergency with heart rate of 54 bpm and ECG evidence of third-degree AV block. What is the immediate management of this patient? A. Digoxin immune Fab B. Lignocaine C. Phenytoin D. DC cardioversion Q5. A patient on digoxin therapy and had a level of 1 ng/ ml. He was receiving several other drugs and presented 2 months later with flattening of T waves in ECG. Now the plasma level of digoxin is 3.8 ng/ml. Which of the following drug is likely to be responsible? A. Triamterene B. Atenolol C. Clarithromycin D. KCl Q6. All of the following drugs are indicated in the treatment of NSTEMI except A. Clopidogrel B. Aspirin C. Streptokinase D. Prasugrel Q7. Which of the following is a K+ Channel Opener? A. Ranolazine B. Nicorandil C. Verapamil D. Quinidine Q8. Which of the following is a late inward sodium channel blocker? A. Ivabradine B. Ranolazine C. Trimetazidine D. Fasudil Q9. Which of the following drug acts at the site marked by arrow as shown in the diagram A. Aliskiren B. Ramipril C. Losartan D. Spironolactone Answers 1. - C 2. - C 3. - B 4. - A 5. - C 6. - C 7. - B 8. - B 9. - B
Ad
38 Cerebellum Quick Revision Notes Q10. Which of the following antihypertensive drug is avoided in patients with high serum uric acid levels? A. Hydrochlorothiazide B. Enalapril C. Prazosin D. Atenolol Q11. A 34 weeks pregnant lady presented with seizures. Her blood pressure is 200/110 mm Hg. Which drugs should be used for the treatment of this patient? A. Oral Labetalol B. IV labetalol plus magnesium sulphate C. IV Lorazepam D. IV Enalapril Q12. Drug used for treatment of pregnancy induced hypertension is A. Alpha methyl dopa B. Lisinopril C. Hydralazine D. Telmisartan Q13. A 56 year old patient who is a known case of hypertension was being treated with antihypertensive drugs. He is having chronic cough since 2 weeks. He was started on antimicrobials but cough did not resolve. Which of the following antihypertensive drug may induce chronic cough in this patient? A. Lisinopril B. Minoxidil C. Propranolol D. Amlodipine Q14. A 26 year old female came to hospital for pre- conceptional counselling. Patient is a known hypertensive compliant to drug therapy. Which of the following drugs will you advise to stop? A. Methyl dopa B. Labetalol C. Lisinopril D. Nifedipine Q15.Identify the correct match regarding the drug and its adverse drug reaction? A. Hydralazine: Heart failure B. Verapamil: Constipation C. Aliskiren: Hypokalemia D. Atenolol: Hemolytic anemia Q16. Resistant hypertension is defined as inability to attain goal blood pressure inspite of the concurrent use of 3 antihypertensive agents of different classes prescribed at optimal doses including A. Alpha blockers B. Diuretics C. Reserpine D. Alpha methyl dopa Q17. A 45 year old patient presented with the symptoms shown in image below. Patient is a known hypertensive and was taking some antihypertensive drug. Which of the following drug is the likely cause of this condition? A. Lisinopril B. Clonidine C. Nifedipine D. Timolol Q18. Which of the following drug should be stopped in a patient with hyperkalemia? A. Losartan B. Furosemide C. Amlodipine D. Hydrochlorthiazide Q19. A patient presents with grade 2 pulmonary artery hypertension. Vaso-reactive stimulation test is negative. Which is the most preferred initial management of this patient? A. Epoprostenol B. Amlodipine C. Alprostadil D. Ambrisentan Answers 10. - A 11. - B 12. - A 13. - A 14. - C 15. - B 16. - B 17. - A 18. - A 19. - D
39 Pharmacology Q20. A 65-year-old man comes to OPD with history of fall. He is hypertensive with history of atrial fibrillation and is presently on captopril, atenolol, aspirin and amiodarone. He presents with the following finding as shown in the image. What is the most probable diagnosis? A. Silver toxicity B. Lupus pernio C. Amiodarone induced skin lesion D. Captopril toxicity Q21. Which of the following antiarrhythmic drug is contraindicated in a patient with interstitial lung disease? A. Amiodarone B. Sotalol C. Quinidine D. Lignocaine Q22. The figure below shows the effect of a drug on the action potential of heart as shown by arrow. Which of the following drug is likely to produce this effect on action potential? A. Quinidine B. Lignocaine C. Esmolol D. Tocainide Q23. Which of the following drug should be avoided in a patient on rosuvastatin therapy? A. Clarithromycin B. Oxycodone C. Rivaroxaban D. Adalimumab Q24. Which of the following hypolipidemic drug acts by inhibition of PCSK-9? A. Atorvastatin B. Evolocumab C. Ezetimibe D. Lomitapide Q25. Which of the following anti-dyslipidemic drugs can result in gall stones? A. Statins B. Bile acid sequestrants C. Niacin D. Fibrates Answers 20. - C 21. - A 22. - A 23. - A 24. - B 25. - D
Ad
PITUITARY HYPOTHALAMIC SYSTEM Anterior Pituitary Hypothalamic control Growth Hormone [GH] GHRH [GH Releasing Hormone] GHIH [GH Inhibiting Hormone] Thyroid Stimulating Hormone Thyrotropin Releasing Hormone Adreno corticotropic Hormone Corticotropin Releasing Hormone Gonadotropins GnRH [Gn Releasing Hormone] Prolactin Prolactin Inhibiting Hormone 1. Growth Hormone Inhibiting Hormones [GHIH] – – It is also known as Somatostatin SOMA TOSTATIN USESQ S → Secretory Diarrohea (Carcinoid syndrome, VIPoma) O → Oesophageal Varices M → Malignancy [Insulinoma, Glucagonoma] A → Acromegaly → Any drug ending with “tide” is peptide. → Any endogenous substance ending with “in” is a peptide e.g; Somatostatin Vasopressin Oxytocin → Peptides cannot be given orally Somatostatin → Short acting therefore not used Octreotide → Long-acting somatostatin derivative → Given by SC route 2. Prolactin Inhibiting Hormone [PIH] = Dopamine [DA] → DA acts through D2 Receptors → Dopamine D2 Agonists decrease prolactin Examples Bromocriptine Cabergoline [Long acting] Uses of Dopamine AgonistsQ Dopamin - Diabetes mellitus type 2 (Bromocriptine) Agonists - Acromegaly (by decreasing GH) Suppress - Suppression of lactation. Plasma - Parkinsonism (Bromocriptine can be used) Prolactin - Hyperprolactinemia Drugs for Acromegaly A. Decreased GH release – – Octreotide – – Cabergoline – – Bromocriptine B. GH receptor antagonist – – Pegvisomant 3. Gonadotropin Releasing Hormone [GnRH] Pulsatile Fashion ↓ ↑ Gonadotropins ↓ ↑ Estrogen ↑ Progesterone ↑ Testosterone Continuous Fashion (Non-pulsatile manner) ↓ ↓ Gonadotropins ↓ ↓ Estrogen ↓ Progesterone ↓ Testosterone Indications of GnRH Pulsatile manner Continuous Fashion 1. Anovulatory infertility 2. Hypogonadotropic hypogonadism 3. Delayed Puberty 1. Carcinoma prostate 2. Endometriosis 3. Precocious Puberty GnRH AgonistsQ 1. Leuprolide 2. Nafarelin (nasal route) 3. Goserelin 4. Busurelin 5. Histarelin → Not effective orally (Mostly given by subcutaneous route) → Flare up Reaction: When these are given in continuous Chapter - 6 Endocrine system
41 Pharmacology manner, for initial few days, there is aggravation of disease GnRH AntagonistsQ 1. Cetrorelix 2. Ganirelix 3. Abarelix 4. Degarelix → No Flare up reaction → But they do not ↑ sex hormones (Used only to ↓ sex hormones) → Not effective orally ELAGOLIX → Recently approved oral GnRH antagonist → Approved for pain due to Endometriosis POSTERIOR PITUITARY → Secretes two main hormones • • Oxytocin • • Vasopressin Oxytocin – – Main function is to contract the uterus • • DOC for augmentation of labour • • DOC for postpartum hemorrhage – – Other function is ejection of milk • • DOC for Breast engorgement Vasopressin – – Also known as anti diuretic hormone (ADH) Vasopressin Receptors V1 Receptor – – Present on BV – – Cause vasoconstriction V2 Receptor – – Present on kidney – – ↓ Urine. Vasopressin Receptor Agonists – – V1 agonist is terlipressin • • DOC for esophageal varicesQ – – V2 agonist is desmopressin • • DOC for neurogenic (central) diabetes insipidus (Given by nasal route)Q Vasopressin Receptor Antagonists – – VAPTANS: VAsoPressin ANTagonistsQ – – Examples Conivaptan - Given via Intravenous route Tolvaptan - Given via Oral route – – Used for SIADH THYROID Hypothyroidism – – DOC is L-thyroxine (T4) – – Started at 25 mcg daily – – Gradually the dose is increased Hyperthyroidism 1. Thyroid Peroxidase Inhibitors (Thioamides) Carbimazole (Prodrug) Methimazole (Active) Propyl Thio Uracil (PTU) → Crosses placenta easily → Less crossing of Placenta → DOC for all patients except in 1st trimester of pregnancy → DOC in 1st trimesterQ → Can cause choanal atresia and aplasia cutis in developing fetusQ → Lesser chance 2. Secretion Inhibitors • Nal • Kl • Lugol’s Iodine → Fastest acting anti-thyroid drugs. → Given preoperatively: – – To make the gland small, firm and less vascular – – To reduce the blood loss during surgery.
Ad
42 Cerebellum Quick Revision Notes 3. Radioactive iodine or I131 → C/I in pregnancyQ → Cause irreversible hypothyroidism → Physical t ½ is 8 days ENDOCRINE PANCREAS Secretes Action Uses α cells Glucagon ↑ Blood Sugar Hypoglycemia β cells Insulin Amylin ↓ Blood Sugar Diabetes mellitus δ cells Somatostatin ↓ Insulin ↓ Glucagon Islet cell tumors GLUCAGON Uses 1. Hypoglycemia → Acts by Glycogenolysis → Not useful in hypoglycemia caused by • • Starvation • • Alcohol induced hypoglycemia 2. Beta- Blocker Poisoning – Glucagon is DOCQ – Acts by stimulating glucagon receptors on heart INSULIN Indications 1. All patients of type 1 DM 2. Uncontrolled patients of type 2 DM 3. Diabetes in pregnancy 4. Diabetic Ketoacidosis Routes of Administration 1. Sub - cutaneous route: – – MC route (because self-administration is possible with this route) – – All insulin preparations can be given by subcutaneous route. – – Site of administration • • Entire abdomen except area around umbilicus (thickness of skin is not uniform, soinsulin absorption is affected) • • Anterior thigh • • Lateral thigh • • Arm 2. Intravenous route: • • Only regular insulin can be given • • So, insulin of choice in diabetic Ketoacidosis → Regular insulin 3. Inhalational route: Afreeza → Short acting insulin → So, should be given before every meal INSULIN ANALOGUES Rapid acting Ultra-Long Acting • • LISPRO • • ASPART • • GLULISINE • • GLARGINE • • DETEMIR • • DEGLUDEC (Longest Acting)Q - These are peakless insulins - These have low risk of hypoglycemia Side Effects 1. Hypoglycemia 2. HypokalemiaQ ORAL ANTI DIABETICS DRUGS 1. Insulin Secretagogues (Act by ↑ Insulin secretion)Q – – These drugs secrete insulin and thus can cause hypoglycemia Sulfonylureas Meglitinides 1st Generation Nateglinide Repaglinide Chlorpropamide Tolbutamide 2nd Generation Glipizide Gliclazide Glibenclamide Drugs ending with “IDE” can cause - hypoglycemiaQ
43 Pharmacology 2. Drugs Acting by Other Mechanisms A. Metformin Adverse effects 1. Megaloblastic Anemia 2. Lactic acidosis Risk of lactic acidosis further ↑, if there isQ – – Liver disease (Gluconeogenesis cannot occur) – – Renal disease (Lactic acid produced cannot be excreted) – – Any condition predisposing to hypoxia (e.g.; Shock, COPD) Thus, metformin is C/I in these patients. Indications → Metformin is DOC for Type 2 DM because: – – No risk of hypoglycemia – – Max. reduction in HbA1cQ – – Can cause weight loss or weight neutral (No weight gain) B. Glitazones E.g. Troglitazone Rosiglitazone Pioglitazone Mechanism ActbystimulatingPPAR-ꝩ → ReversalofInsulinResistance Adverse Effects 1. Hepatotoxic → Max. hepatoxicity → Troglitazone [withdrawn]Q → Rosiglitazone and Pioglitazone require LFT monitoringQ 2. Na+ and water Retention → Avoid in CHF and HTNQ 3. Predispose to osteoporotic fractures. 4. ↑ Risk of Ml by rosiglitazone 5. ↑ Risk of urinary bladder carcinoma by PioglitazoneQ C. Acarbose → Act by inhibiting the intestinal absorption of carbohydrates (blood sugar decreases) → Does not cause hypoglycemia → Flatulence → MC side effect → C/I in lnflammatory bowel diseaseQ • • Ulcerative colitis • • Crohn’s disease NEW ANTIDIABETIC DRUGS 1. Incretin – Mimetics → Incretins are normal physiological substances which are released in GIT after food intake that stimulate the release of insulin. → Most important endogenous incretins are GLP (Glucagon like peptide) and GIP (Glucose stimulated insulinotropic polypeptide) → Functions of Incretins: – – Increase insulin release – – Decrease gastric motility → GLP is metabolized by DPP-4 and becomes inactive A. GLP analogues: → Given subcutaneously (Cannot be given orally since these are peptides) GLP-1 analogues : Used for type 2 DMQ – – Exenatide – – Liraglutide GLP-2 analog : Used for short bowel syndromeQ – – Teduglutide Side effects – – Acute pancreatitis (Major side effect) – – Increased risk of Medullary carcinoma of Thyroid
Ad
44 Cerebellum Quick Revision Notes B. DPP - 4 inhibitors: a. Sitagliptin b. Vildagliptin c. Alogliptin d. Linagliptin → Gliptins are oral anti - diabetic drugs. – – Pancreatitis is the major adverse effect – – Gliptins are contraindicated in renal failure except Linagliptin which is safe in renal failure 2. SGLT-2 Inhibitors: → Glucose is freely filtered by glomerulus but the clearance of glucose in urine is negligible. → Because the reabsorption takes place in proximal tubule by sodium glucose transporter (SGLT-2) → SGLT-2 inhibitors stop the reabsorption of glucose in PT resulting in glucosuria. Drugs areQ – – Canagliflozin – – Dapagliflozin – – Empagliflozin – – Ertugliflozin – – Most common side effect of SGLT-2 Inhibitors is Urinary Tract infections – – SLGT-2 inhibitors provide cardiovascular benefits. These are approved for treatment of CHF. 3. Amylin Analogs: → Amylin is secreted form β - cells of pancreas. → Function of amylin is to ↓ blood sugar. → Pramlintide is an amylin analogue → It is approved for both type 1 and 2 diabetes. 4. BromocriptineQ → Decreases insulin resistance and it has been recently approved for type 2 diabetes treatment. → Given in small dose and taken at early morning on awakening. ADRENAL Adrenal Medulla Adrenal Cortex → Secretes – – Adrenaline – – Nor-Adrenaline – – Dopamine → Secretes – – Glucocorticoids – – Mineralocorticoids Mineralocorticoids Aldosterone → Major endogenous Mineralocorticoid Actions – Retain Na+ and water – Remove K+ and H+ Glucocorticoids Hydrocortisone → Major endogenous Glucocorticoid CLASSIFICATION OF DRUGS Glucocorticoids Mineralocorticoids Short Acting (<12 hours) Cortisone Hydrocortisone Aldosterone Fludrocortisone DOCA Intermediate Acting (12-36 hours) Prednisone Prednisolone Triamcinolone Long Acting (> 36 hours) Dexamethasone Betamethasone Paramethasone Special PointsQ Property Drug Maximum G activity Dexamethasone Maximum M activity Aldosterone G with max M activity Hydrocortisone M with max G activity Fludrocortisone Selective G Triamcinolone Dexamethasone Betamethasone
45 Pharmacology Selective M DOCA Note: G means glucocorticoid (anti-inflammatory) M means mineralocroticoid (Na+ and H2 O retaining) Uses of Corticosteroids Antenatal Replacement Other Uses Dexa / Betamethasone for fetal lung maturity (Glucocorticoids increase surfactant production) Acute Adrenal insufficiency / Addisonian crisis [by IV] Chronic Adrenal lnsufficiency / Addison’s disease [by oral] Inflammation Auto immune diseases Transplantation Anticancer therapy Asthma Ante Natal Steroids Total dose Total duration Betamethasone → IM 12 mg every 24 hrs. x 2 DosesQ 24 mg 48 hrs. Dexamethasone → IM 6 mg every 12 hrs. x 4 Doses 24 mg 48 hrs Hypothalamo-Pitutary-Adrenal Axis [HPA Axis] HPA Axis Suppression → Occurs when corticosteroids are given continuously for > 2wks Preventive Measures 1. Stop unnecessary use of steroids 2. If indicated, prescribe them for minimum period preferably < 2wks 3. If indicated for long periods, prescribe them on alternate day – – Long-acting steroids (dexa, beta and paramethasone) are avoided 4. If indicated daily and for longer periods – – Don’t Stop Abruptly – – Tapering should be done Adverse effects Major adverse effect is Cushing syndrome OSTEOPOROSIS Nutritional factors – Calcium – Vitamin D Inhibit osteoclast – Calcitonin – Estrogens – SERMs – Denosumab – Cinacalcet Stimulate osteoblast – PTH 1-34 Drugs used in Osteoporosis Dual action – Strontium – Romosozumab Nutritional Factors – – Calcium is given at a dose of 1200 mg/day (It includes dietary calcium) – – Vitamin D should be given as 800 IU per day Drugs Inhibiting Osteoclast 1. Calcitonin: Given Intranasally 2. BisphosphonatesQ Alendronate Risedronate Zoledronate – – Inhibit osteoclasts – – DOC for Osteoporosis [Osteoporosis due to any reason]
Ad
46 Cerebellum Quick Revision Notes – – These are indicated for a period of maximum 10 years – – Highly toxic to esophagus Prevention of OesophagitisQ – Take empty stomach – Take with full glass of water – Remain upright for 30 min 3. Estrogen and SERM Decreased estrogen is responsible for post- menopausal osteoporosis Actions of Estrogen Bone → Prevent resorption Blood → ↑ HDL/LDLRatio Breast → ↑ Risk of Carcinoma Endometrium → ↑ Risk of Carcinoma Liver → ↑Clotting Factors→ Thromboembolism → Not preferred for Rx of PM Osteoporosis RaloxifeneQ – – It is selective estrogen receptor modulator – – It has agonist action on ER in bone, blood and liver whereas antagonistic action on breast and endometrium – – Used in post menopausal osteoporosis – – AdditionalBenefits • • ↑ HDL • • ↓ Breast and Endometrial carcinoma risk – – Major S/E → Thromboembolism 4. Denosumab DRUGS STIMULATING OSTEOBLASTS 1. Teriparatide – – Parathyroid hormone contains 84 amino acids (i.e., PTH1-84). – – Full molecule stimulates osteoclast and induces osteoporosis by resorption of bone. – – Teriparatide is a fraction of parathyroid (PTH 1-34) that stimulates Osteoblast and is used for osteoporosis treatment.Q – – Route of administration - Not effective orally (given subcutaneously) – – PTH 1-34 is recommended for maximum 2 years. – – Treatment with PTH 1-34 should be followed by bisphosphonates. DRUGS WITH DUAL ACTIONQ – – These have dual activity of stimulating osteoblast and inhibiting osteoclast – – Strontium ranelate and romosozumab act by dual mechanism – – Romosozumab is a monoclonal antibody against sclerostin ANDROGENS – – 5 α reductase converts testosterone into Dihydrotestosterone (DHT) which works on androgen receptors. Testosterone also can directly work on androgen receptors. – – In treatment of prostatic cancer androgen receptor blockers are commonly used. – – In treatment of BPH and androgenital alopecia (Male pattern baldness): 5 α-reductase inhibitors like finasteride are used. – – On the surface of osteoclast cells, RANK receptors are present. When ligand binds to RANK receptors, it stimulates the resorption of bone. – – Denosumab is a monoclonal antibody against RANK ligand. It inhibits the osteoclastic activity and resorption of bone.Q
47 Pharmacology – – Both the class of drugs can cause impotence as an adverse effect ORAL CONTRACEPTIVES 1. COMBINED ORAL CONTRACEPTIVE PILLS → Drugs • • Estrogen - Ethinyl Estradiol • • Progesterone - Levonorgestrel → Dosage • • 1 tablet daily for 21 days from 1st day of menstrual cycle • • No tablet for next 7 days • • To ↑ compliance: 28 tablets strip with 1st 21 tablets contains drug and next 7 tablets contains iron → Missed Tablets If one tablet is missed Take 2 tablet on next day If 2 or more tablets missed • • Discard remaining tablets • • Practice other method of contraception with it. • • Start a fresh from next cycle 2. POP / MINIPILLS – – Used where Combined OCPs cannot be used – – Contains LNG – – OCP of choice in lactationQ 3. EMERGENCY CONTRACEPTIVES A. Combined Oral Contraceptives B. Progesterone Only Pills [LNG] C. Mifepristone Above 3 drugs should be used with in 72 hrs. of unprotected intercourse. D. Ulipristal → Can be used within 120 hours of unprotected intercourse NON CONTRACEPTIVE BENEFITS OF OCPs Other→ ↓ Ovarian cyst [DOC for PCOD] B → ↓ Benign Breast Disease E → ↓ Endometriosis N → ↓ Neoplasia[Endometrial and ovariancancers] E → ↓ Ectopic pregnancy F → ↓ Fibroid I → ↓ Iron deficiency Anemia T → ↓ Premenstrual Tension Syndrome S → ↓ Skeletal Disease [Osteoporosis] ↑ Risk of – – Cervical Ca – – Breast Ca ↓ Risk of – – Endometrial Ca – – Ovarian Ca OCPs POLYCYSTIC OVARIAN DISEASE (PCOD) – – OCPs are DOC for regulating the menstrual cycle in PCOD – – Metformin is used to reverse insulin resistance – – Ovulation inducers are used to induce ovulationQ • • Aromatase inhibitors e.g. letrozole is DOC • • Clomiphene citrate can also be used.
Ad
48 Cerebellum Quick Revision Notes Q6. A 28 year old female with Graves’ disease was taking medication for hyperthyroidism during pregnancy. She delivered a child with congenital anomaly ‘aplasia cutis congenita’. Most likely drug implicated for this teratogenic effect is? A. Carbimazole B. Levo-thyroxine C. Methylthiouracil D. Liothyronine Q7. Drug of choice for hyperthyroidism in third trimester of pregnancy is A. Carbimazole B. Propylthyouracil C. Sodium iodide D. Radioactive iodine Q 8. A 30 year old female presented with weight gain and cold intolerance. On investigations Value of T3 is 70 ng/dl (reference value 100-200 ng/dl),T4 is 3 mcg/ dl (reference value 5-12 mcg/dl) and TSH is 20 mIU/L (reference value 0.5-5 mIU/L). Which of the following statement is correct regarding the management of this patient? A. Measure T3, T4 and TSH after one month B. Start L-thyroxine (T4) treatment 100 mcg once daily C. Start L-thyroxine (T4) treatment 25 mcg daily and gradually increase D. Start daily L-thyroxine (T4) 100 mcg with Liothy- ronine (T3) 5 mcg Q 9. What is the Drug of choice for Hyperthyroidism in first trimester of Pregnancy? A. Lugol’s iodine B. Methimazole C. Propylthiouracil D. Carbimazole Q 10. Which of the following drug is given pre-operatively to decrease the risk of intraoperative bleeding in a hyperthyroid patient planned for thyroidectomy? A. Potassium iodide B. Propranolol C. Propylthiouracil D. Methimazole Previous Years Questions Q1. A patient was operated for prostate carcinoma and during surgery local metastasis was noted. Which of the following drug this patient should receive? A. Leuprolide B. Desmopressin C. Octreotide D. Tamsulosin Q2. Tolvaptan is used for: A. SIADH B. Central Diabetes Insipidus C. Von Willebrand Disease D. Catecholamine resistant Shock Q3. A patient presents with pituitary tumor that overproduces growth hormone. surgical removal of the tumor was incomplete. What is the first line treatment of this patient? A. Leuprolide B. Octreotide C. Nafarelin D. Goserelin Q4. A 40 year old male presents with protrusion of chin, excessive sweating, impaired glucose tolerance and enlargement of hands and feet? Which of the following drugs is a growth hormone receptor antagonist used to treat this condition? A. Pegvisomant B. Octreotide C. Cabergoline D. Olcegepant Q5. A female presented with galactorrhea. Her urine pregnancy test was negative. MRI of head revealed a large pituitary tumor. Patient refused to undergo surgery for the tumor. Which of the following is the best drug for the treatment of this patient? A. Octreotide B. Bromocriptine C. Promethazine D. Clozapine Answers 1. - A 2. - A 3. - B 4. - A 5. - B 6. - A 7. - A 8. - C 9. - C 10. - A
49 Pharmacology Q 16. Which of the following drug is given to mother delivering premature baby for fetal lung maturation? A. Aspirin B. Dexamethasone C. Magnesium sulfate D. Depot medroxy progesterone acetate Q 17. A patient presented with the following features after chronic intake of a drug for several years. Which is the likely drug person has consumed? A. Paracetamol B. Prednisolone C. Phenytoin D. Metformin Q 18. What is the prenatal dose of dexamethasone given for lung maturation in premature infants ? A. 6 mg 2 doses 12 hours apart B. 12 mg 2 doses 24 hours apart C. 6 mg 4 doses 12 hours apart D. 6 mg 4 doses 24 hours apart Q 11. A 70 year old patient has diabetes mellitus and hypertension. He presents with late stage chronic kidney disease. Which of the following anti-diabetic drugs require least dose modification in renal disease? A. Sitagliptin B. Vildagliptin C. Linagliptin D. Saxagliptin Q 12. A 50 year old patient of type 2 diabetes mellitus was controlled on oral hypoglycemic drugs. This patient presented to hospital with profuse sweating and dizziness. There was presence of hypoglycemia. Which among the following drugs can result in hypoglycemia in this patient? A. Metformin B. Voglibose C. Vildagliptin D. Glipizide Q 13. Which of the following anti-diabetic drugs is associated with increased risk of fractures in a female with osteoporosis? A. Canagliflozin B. Rosiglitazone C. Voglibose D. Rapaglinide Q 14. Mechanism of action of exenatide in diabetes mellitus is A. It is analogue of GLP released from gut and in- crease glucose dependent insulin secretion B. It is DPP-4 inhibitor and result in decreased breadkdown of GLP C. It inhibits SGLT-2 and cause glucosuria D. It is amylin analogue and decrease glucagon Q 15. To minimize the risk of HPA axis suppression, what is the correct method of administration of prednisolone? A. Give at night just before bedtime B. Divide in three doses and give small doses 8 hourly C. Give on alternate day D. Replace with betamethasone Answers 11. - C 12. - D 13. - B 14. - A 17. - B 18. - C 15. - C 16. - B
Ad
50 Cerebellum Quick Revision Notes Q 19. Which of the following is not used in treatment of polycystic ovarian disease? A. Letrozole B. Clomiphene citrate C. Ulipristal D. Combined oral contraceptives Q 20. Combined oral contraceptive pills act by all of the following mechanisms except? A. Inhibit implantation by bringing change in the uterus B. Inhibit ovulation C. Makes cervical mucus thick and hostile D. Increase gonadotropin secretion Answers 19. - C 20. - D 21. - A 22. - A Q 21. A 22 year old female presents 8 hours after sexual assault. It is the 13th day of her menstrual cycle. Which emergency contraceptive should be prescribed to her? A. Levonorgestrel 1.5 g single tablet B. Injection DMPA C. OCP from day 1 of next cycle D. Misoprostol Q 22. Which of the following is not used as emergency contraceptive? A. Danazol B. Levonorgestrel C. Mifepristone D. IUCD
Chapter - 7 Central Nervous System NEURODEGENERATIVE DISEASES These occur due to age related degeneration of neurons ALZHEIMER’S DISEASE – – It occurs due to age related degeneration of cholinergic neurons in basal nucleus of Meynert. – – Aβ-amyloid deposition is the underlying cause of neuronal degeneration. – – It is characterized by loss of memory (Dementia) DRUGS USED 1. AChE inhibitors:Q Lipid soluble drugs which have very high entry in the brain are preferred. Donepezil Rivastigmine These are DOC for Alzheimer’s dementia Gallantamine 2. NMDA receptor antagonist: – – Memantine is an NMDA receptor antagonist.Q 3. Monoclonal Antibody against Aβ-amyloid: – – Aducanumab targets the underlying cause i.e., Aβ-amyloid PARKINSONISM – – In Parkinsonism, there is deficiency of dopaminergic activity in basal ganglia of brain – – Normally, there is balance b/w dopaminergic (DA) and cholinergic (ACh) neurons – – In Parkinsonism, this balance is lost [Relative cholinergic excess] Two ways to treat Parkinsonism A. Increase dopamine B. Decrease Ach A. DOPAMINERGIC DRUGS 1. Levo-dopa Peripheral DOPA decarboxylase convert L-dopa to Dopamine. So if given alone: → Less efficacious due to less entry in brain. → DA produced outside the brain causes peripheral side effects like
Ad
52 Cerebellum Quick Revision Notes Carbidopa Benserazide ↓ ↑ Efficacy ↓ Peripheral S/E Psychosis – – Dyskinesia – – Abnormal behavior → Psychosis can occur due to excessive DA in brain – – Central S/E of levodopa cannot be prevented by carbi-dopa → Central S/E of levopa cannot be prevented by carbi-dopa 2. AmantadineQ – – Acts by releasing DA from vesicle – – Can Cause ankle edema (reversible) and Livedo reticularis (Pinkish pigmentation of skin in form of meshwork) – – Recently approved for treating Levo-dopa induced Dyskinesia as Amantadine acts as a NMDA Antagonist (Only anti Parkinsonian drug to treat dyskinesia) 3. Metabolism Inhibitors Selective MAO-B Inhibitors : Selegiline COMT Inhibitors : Entacapone 4. Dopamine Agonists → Directly works on dopamine receptors – – Pramipexole and ropinirole are DOC for Parkinsonism B. ANTI-CHOLINERGIC DRUGS → These are DOC for Drug Induced Parkinsonism Peripheral DOPA Decarboxylase inhibitors Two groups: 1. Central Anti-cholinergics: Benzhexol [Trihexyphenidyl] 2. First Generation Anti-histaminic drugs: Promethazine MULTIPLE SCLEROSIS – – Demyelinating disease Condition DOC Acute Episode Relapsing Remitting (RRMS) Primary Progressive (PPMS) Intravenous Steroids β-IFN Ocrelizumab EPILEPSYQ Seizure Special Feature First Line Drug GTCS Valproate, Lamotrigine Absence EEG shows 3 spike / wave pattern Valproate, Ethosuximide Focal Temporal lobe Carbamazepine (DOC) Oxcarbazepine Levetiracetam, (DOC in elderly) Myoclonic Valproate Atonic Valproate Lennox Gastaut Syndrome Valproate, Rufinamide Febrile seizures Diazepam Status Epilepticus Lorazepam Infantile spasms Also called Salaam seizures Seen in West syndrome ACTH (DOC), Vigabatrin Eclamptic seizures Due to high BP in pregnancy MgSO4 (DOC) • • First sign of toxicity is loss of deep tendon reflexes like patellar reflex Epilepsy in pregnancy - • • Don’t change drug if female is already controlled on any AED • • Least teratogenic are lamotrigine and levetiracetam – – Hypotension – – Arrhythmias – – Hypertension – – Vomiting
53 Pharmacology Lamotrigine – – DOC for focal seizures in elderly (along with levetiracetam) – – Side effects: • • Steven Johnson SyndromeQ • • Toxic Epidermal Necrolysis These side effects can be avoided by gradually increasing the dose. Sodium Valproate It can cause adverse effects like: – – Liver damage – – PancreatitisQ – – PCOD Phenytoin Adverse Effects H - Hirsutism, Hypertrophy of gums O - Osteomalacia T - Teratogenicity [Fetal Hydantoin syndrome] M - Megaloblastic Anemia [↓ Folate]Q A - Arrhythmia [Only in overdose] L - Lymphnode enlargement I - ↓ insulin (avoided in DM)Q K - ↓ Vitamin K A -Ataxias,vertigo[cerebellar symptoms] [only athighdose] Topiramate – – Can cause renal stone – – Other uses of Topiratmate (COMB) – – Craving of Alcohol – – Obesity – – Migraine prophylaxis – – Bipolar disorder Vigabatrin Retigabine – – Used or Focal seizures – – Does not act on GABA – – Can cause retinitis as side-effect. Other uses of AEDs Bipolar disorder CBZ, Valporate, Topiramate Migrane prophylaxis Topiramate, Valproate Neuropathic pain Gabapentin, Pregabalin, CBZ Restless leg syndrome Gabapentin (DOC) Arrhythmias Phenytoin ANTI-PSYCHOTIC DRUGS – – Psychosis occurs due to excessive dopamine in brain. – – Anti-phychotics drug can be divided into: 1. Typical Anti Psychotics [D2 Blockers] 2. Atypical Anti Psychotics [any other mechanism; mainly 5HT2 Blockers] Typical Antipsychotics 1. Strong D2 # – – Haloperidol [Highest risk of EPS] 2. Weak D2 # – – Chlorpromazine Side effects 1. Extra Pyramidal Symptoms [EPS] Extra Pyramidal Symptom Drug of choice 1. Dystonias [Earliest]Q Benzhexol 2. Akathisia [MC]Q Propanolol 3. Parkinsonism Benzhexol 4. Tardive dyskinesia [Very late to appear]Q Valbenazine 5. Malignant Neuroleptic Syndrome Dantrolene 2. Hyperprolactinemia – – Dopamine ↓ prolactin by stimulating D2 receptors. Therefore, antipsychotics can cause hyperprolactinemia due to D2 blockade. – – Hyperprolactinemia can result in galactorrhea and infertility
Ad
54 Cerebellum Quick Revision Notes Atypical Anti Psychotics Advantages 1. Lesser risk of EPS and hyperprolactinemia 2. Effective against both Positive as well as negative symptoms Side effects – Causelipodystrophysyndromecharacterized by • • ↑ Glucose • • ↑ Lipids • • Weight gain • • Insulin Resistance – Risk is highest with clozapine Clozapine → DOC for resistant Schizophrenia → Adverse effects are: – – Agranulocytosis [Dose independent]Q – – Seizures [Dose dependent] – – Myocarditis – – Sedation (Most common adverse effect) – – Sialorrhea (MC side effect)Q ACUTE MANIA – – Patient is usually aggressive and violent – – Rx of Acute Episode: Sedatives [Antipsychotics/ BZD] + Lithium – – Prophylaxis: Lithium is DOC. – – Bipolar disorder: DOC is lithiumQ Lithium Pharmacokinetics – – Half-life is 24 hours – – Narrow Therapeutic Index – – Given thrice a day Therapeutic drug monitoring Interactions Drug increasing toxicity are: – – Lisinopril – – Indomethacin – – Thlazides Toxicity (DAT) – – Diarrhea – – Agitation & Incordination – – Tinnitis Actions of LithiumQ L - Leucocytes I - Increase T - Tremors [MC] H - Hypothyroidism I - Increase U - Urine M - Avoided in Mothers [Lithium in pregnancy → Ebstein anomaly] DEPRESSION – – Earlier it was believed, decrease in Monoamines (5-HT > NA» DA) causes depression. – – Later it was linked with decrease in BDNF i.e., when ↑ Monoamines – – ↑ BDNF → ↑ Neuro Plasticity → ↓ Depression ANTI DEPRESSANTS – – Typical Anti-Depressants → Act by ↑ 5HT – – Atypical Anti-Depressants → Act by other mechanisms Typical Antidepressants These may be: 1. MAO - A Inhibitors – – Moclebemide – – Reversible inhibitors of MAO-A]Q Leukocytosis Polyuria – – For measuring plasma concentration: Sample taken at 12 hours after last dose. – – Plasma concentration of LithiumQ • • Acute mania → 0.8-1.2 mEq/L • • Prophylaxis → 0.5-0.8 mEq/L
55 Pharmacology 2. Reuptake Inhibitors Non Selective Selective • • Inhibit reuptake of 5HT and NA • • Avoided in cardiac patients • • Indicated For severe depression • • Inhibit reuptake of 5HT • • Can be used in cardiac patients • • Indicated for mild to moderate depression A. Non-Selective Reuptake Inhibitors – – Inhibit the reuptake of both 5HT and NA – – Two classes: TCA and SNRI (i) TCA [Tricyclic antidepressants] – – Imipramine – – Desipramine – – Clomipramine – – Amitriptyline – – Nortriptyline → Adverse Effects: • • ACh#: Dry mouth, blurred vision, C/I in glaucoma • • α #: Postural hypotension • • H1 #: Sedation • • Seizures • • Arrhythmias • • Metabolic acidosis → Treatment of TCA poisoning: • • NaHCO3 to correct metabolic acidosis and reverse arrhythmiasQ (ii) SNRI [Serotonin Noradrenaline Reuptake Inhibitors] – – ↑ 5 HT and ↑ NA – – Lesser adverse effects than TCAs. – – DOC for severe depression → Drugs – – Venlafaxine – – Duloxetine – – Milnacipran – – Desvenlafaxine – – Levo-Milnacipran B. Selective Serotonin Reuptake Inhibitors → Drugs – – Fluoxetine – – Paroxetine – – Fluvoxamine – – Sertraline – – Citalopram – – Es-Citalopram – – Dapoxetine → For premature ejaculationQ Indication of SSRI • • SSRI are DOC for mild-moderate depression • • SSRI are DOC for all neurotic disorders like – – GAD – – OCD – – Bulimia – – Phobia – – PTSD – – Impulse control disorders Adverse Effects of SSRI – – Nausea (Most common) – – Anxiety (Due to up-regulation of 5HT2 receptors) – – CNS: Headache, bad dreams – – Sexual:Q • • Due to 5HT2 receptor stimulation • • Include ○ ○ Anorgasmia ○ ○ Delayed ejaculation (Dapoxetine used for Pre mature ejaculation) • • Discontinuation syndrome (Least with Fluoxetine)Q
Ad
56 Cerebellum Quick Revision Notes Atypical Anti-Depressants – – Less sexual side effects → Drugs – – Bupropion - Anti-Smoking drugQ – – Amineptin - ↑ Reuptake of 5-HT – – Tianeptin - ↑ Reuptake of 5-HT – – Vortioxetine – – Vilazodone – – Esketamine – – Brexanolone Esketamine – – Acts by blocking NMDA receptors of Glutamate – – Used as a Nasal spray for treatment resistant depression Brexanolone/ Allopregnanolone Approved for Post-partum depression. DRUG OF ABUSE Opioids Morphine – – Acts on µ, K, δ Receptors – – Stimulation of µ, K, δ Receptors cause – Analgesia µ Receptor FunctionsQ S - Sedation A – Analgesia C – Constipation R - Respiratory depression U - eUphoria M – Miosis Kappa receptors cause dysphoria Important Drugs: Morphine is used to treat pain but it should not be used to treat Biliary colic because morphine causes spasm of sphincter of Oddi which increases the intra biliary pressure that can result in rupture of bileduct.Q Tramadol → Two MOA – – Agonist at µ, k, δ receptors (opioid action) – – ↑ 5HT and NA in spinal cord (Non-opioid action) Naloxone cannot completely abolish the analgesic effect of tramadol and tapentadol Fentanyl – – Highly lipid soluble drugs – – Used for anesthesia – – Cause Post operative muscle rigidity. It is also known as Wooden chest syndrome ANTAGONISTS → Drugs Naloxone - Short acting, given IVQ Naltrexone - Long acting, given Orally DOC for acute Opioid poisoning → Naloxone DOC for maintenance in opioid poisoning → NaltrexoneQ
57 Pharmacology A. Sedation B. Sudden death C. Weight gain D. Skin rash Q 8. Which of the following combination of seizure and its first line drug is not correct? A. Generalized seizure - Valproate B. Myoclonic - Phenytoin C. Focal – Carbamazepine D. Absence - Ethosuximide Q 9. Topiramate is used for the treatment of A. Lennox Gastaut syndrome B. Attention deficit hyperkinetic disorder C. Treatment of migraine D. Prophylaxis of heat stroke Q 10. A young boy was brought to hospital with complaints of few episodes of fast blinking and staring at something for around 20 seconds. ECG shows spike and wave pattern. Which of the following drug should be used for treatment? A. Phenytoin B. Sodium valproate C. Diazepam D. Carbamazepine Q11. ACTH is the treatment of A. Juvenile myoclonic epilepsy B. West syndrome C. Dravet syndrome D. Lennox Gastaut syndrome Q 12. Which of the following anti-epileptic drug is used in treatment of neuropathic pain ? 1. Gabapentin 2. Lamotrigine 3. Carbamazepine 4. Pregabalin A. 1 and 2 B. 2 and 3 C. 1, 2 and 3 D. 1, 3 and 4 Previous Years Questions Q 1. An elderly male developed the symptoms of dementia and was diagnosed as Alzheimer’s disease. Which neurotransmitter level is reduced in this disease? A. Dopamine B. Acetylcholine C. Adrenaline D. Serotonin Q 2. An elderly patient presented with tremors, rigidity and bradykinesia. The most likely neurotransmitter affected in the brain of this patient is? A. Dopamine B. GABA C. Adrenaline D. Serotonin Q 3. Which of the following drug is the only medication useful in preventing disability progression in a patient with primary progressive multiple sclerosis? A. Natalizumab B. Ocrelizumab C. Siponimod D. Rituximab Q 4. A patient presents with tremors, rigidity and bradykinesia. Which of the following drugs can be used for the treatment of this patient? A. Selegiline B. Donepezil C. Fluoxetine D. Haloperidol Q 5. A patient is on long term anticonvulsant therapy. There is progressive contractility of visual field. The likely anti-epileptic drug responsible for this adverse effect is A. Vigabatrin B. Ethosuximide C. Phenobarbital D. Levetiracetam Q 6. Least teratogenic antiepileptic drug in pregnancy is A. Valproate B. Phenytoin C. Carbamazepine D. Levetiracetam Q 7. A patient was started on lamotrigine 50 mg daily for treatment of epilepsy. Gradually, the dose of the drug is increased every 1-2 weeks to reach the final dose of 200 mg per day. This step up titration of lamotrigine dose is done in order to prevent or minimize the development of Answers 1. - B 2. - A 3. - B 4. - A 5. - A 6. - D 7. - D 8. - B 9. - A 10. - B 11. - B 12. - D
Ad
58 Cerebellum Quick Revision Notes Q 19. A 30 year old patient was started on lithium carbonate for bipolar disorder. The nurse will gave instructions on adverse effects of the therapy. The patient should report back if the following features are seen: A. Palpitations, chest pain, raised blood pressure B. Sedation, constipation, vomiting C. Tinnitus, severe diarrhea, ataxia D. Fever, skin rash, bradycardia Q 20. For plasma level monitoring, lithium estimation is done? A. Immediately after the dose B. 8 hours after last dose C. 12 hours after last dose D. 24 hours after last dose Q 21. A 25 year old female presented with mania. History revealed that her father is taking medications for bipolar disorder. Which of the following drug will you prescribe for this patient? A. Sodium valproate B. Lithium C. Carbamazepine D. Lamotrigine Q 22. Which of the following anti-depressant drug acts by inhibiting the reuptake of both serotonin and nor- adrenaline? A. Fluoxetine B. Venlafaxine C. Phenelzine D. Nortriptyline Q 23. A patient had a history of previous child with down syndrome, currently on lithium therapy present for antenatal checkup. Which of the following condition is the fetus at the greatest risk of? A. Ebstein’s anomaly B. Down’s syndrome C. Tetralogy of Fallot D. Neural tube defect Q 24. A 30 year old female presented to psychiatry OPD with symptoms of hypomania. She has a past history of mania and wants to conceive. Which of the following drug is most teratogenic? Q 13. A child born by normal vaginal delivery developed repeated attacks of flexion of neck over the trunk and jerks in the hands. EEG shows the presence of hypsarrhythmia. Anti-epileptic drug of choice for this patient is? A. Phenobarbitone B. Phenytoin C. ACTH D. Levetiracetam Q 14. First sign of MgSO4 toxicity is A. Loss of patellar reflex B. Respiratory distress C. Cardiac arrest D. Decrease in urine output Q 15. Which of the following adverse effect is more with oxcarbazepine as compared to carbamazepine? A. Thrombocytopenia B. Dilutional hyponatremia C. Rash D. Hepatotoxicity Q 16. A patient of psychosis was being treated with risperidone. He presented to emergency with upward fixed gaze. What will be the treatment of this patient? A. Wait and assurance B. Intramuscular Promethazine C. Injection Diazepam D. Injection Lorazepam Q 17. A patient was recently started on Fluphenazine. Few weeks later, he developed tremors, rigidity, bradykinesia and excessive salivation. First line of management for this patient is A. Selegiline B. Trihexyphenidyl C. Pramipexole D. Amantadine Q 18. A psychotropic drug inhibiting the reuptake of serotonin is likely to cause which of the following adverse effect? A. Visual disturbance B. Constipation C. Dry mouth D. Sexual dysfunction Answers 13. - C 14. - A 15. - B 16. - B 19. - C 20. - C 23. - A 24. - A 17. - B 18. - D 21. - B 22. - B
59 Pharmacology Q 30. Whichofthefollowing issafeplasmaconcentration of lithium for treatment of acute attack and prophylaxis of migraine? A. 0.6-1.2 mEq/L B. 0.6-1 mEq/L C. 2-3 mEq/L D. 1-2 mEq/L Q 31. A patient suffering from depression has to be started on anti-depressant drug. Which of the following is least likely to cause sexual side effects? A. Venlafaxine B. Escitalopram C. Imipramine D. Bupropion Q 32. A 22 year old female with bipolar disorder was on lithium therapy. Which of the following statements about the therapy is not correct A. Hemodialysis is not useful in lithium overdose B. Lithium decreases thyroid function C. Lithium toxicity is increased by thiazides D. Lithium is avoided in pregnancy due to its teratogenic effects Q 33. Which of the following drug used for pain relief in arthritis acts by both opioid and non opioid mechanisms? A. Paracetamol B. Tramadol C. Ketorolac D. Diclofenac A. Valproate B. Lithium C. Carbamazepine D. Olanzapine Q 25. Which of the following is a novel antidepressant drug? A. Vilazodone B. Asenapine C. Flibanserin D. Lurasidone Q 26. Which of the following antidepressant drug should be avoided in a patient of angle closure glaucoma? A. Sertraline B. Amitriptyline C. Mirtazapine D. Venlafaxine Q27.Apatientonanti-depressanttherapypresentswith elevated body temperature, dilated pupil, palpitations and low blood pressure. ECG shows tachycardia, broad QRS complex and right axis deviation. Which of the following interventions must be done immediately? A. Wait and watch B. Intravenous sodium bicarbonate C. Intravenous esmolol D. DC cardioversion Q 28. A patient on lithium therapy developed hypertension. He was started on thiazides for hypertension. After few days, he developed coarse tremors and other symptoms suggestive of lithium toxicity. Explain the likely mechanism of this interaction. A. Thiazide inhibits the metabolism of lithium B. Thiazides act as an add on drug to lithium C. Thiazides increase the tubular reabsorption of lithium D. Thiazides cause loss of water thereby increase lithium levels. Q 29. A female patient was on lithium therapy for bipolar disorder for 6 months. She kept the fast for few days due to religious reasons and presented with seizures, coarse tremors, confusion and weakness of limbs. Which of the following should be done to diagnose her condition? A. Serum Electrolytes B.Serum lithium levels C. ECG D. MRI Answers 25. - A 26. - B 27. - B 28. - C 29. - A 30. - A 31. - D 32. - A 33. - B
Ad
DRUGS AFFECTING BLOOD FLOW ANTI PLATELET DRUGS Chapter - 8 Hematology 1. Aspirin Inhibit COX → ↓TXA2 2. Clopidogrel Ticlopidine Acts on ADP 3. Abciximab Tirofiban Eptifibatide Act on GP IIb/IIIaQ 4. Atopaxar Vorapaxar Act on PAR-1 receptors of thrombinQ ANTI COAGULANTS These are divided into oral and parenteral anticoagulants Oral Anti-Coagulants • • Vitamin K inhibitors • • Direct thrombin inhibitors • • Factor Xa inhibitor 1. Vitamin K inhibitors → Includes dicumarol and warfarin Properties of Warfarin: 1. Oral anticoagulant 2. Inhibit vitamin - K 3. Takes 4-5 days to produce action 4. Mainly used for maintenance purpose 5. Contraindicated in pregnancy 6. Effect of Warfarin is monitored by PT/INR Warfarin Overdose: • • Overdose of Warfarin causes bleeding • • Active Factors like IIa, VIIa, IXa, Xa (which are Known as Four Factor complex (or) Prothrombin Factor complex) is the Treatment of choice.Q • • If Four Factor complex is not available, then fresh frozen plasma can be used. • • If the fresh frozen plasma is also not available, whole blood should be given • • But the Treatment of choice for bleeding tendency due to warfarin is Vitamin K • • Vitamin K is also antidote for Warfarin overdose. 2. Direct Thrombin Inhibitors • • Dabigatran - Can be given Orally and does not require monitoringQ 3. Direct factor Xa inhibitors Drugs are • • Rivaroxaban • • Apixaban • • Edoxaban • • Betrixaban RIVAR – REVERSIBLE O – ORAL XA – XA B – BLOCKER (OR) AN – ANTAGONIST
61 Pharmacology Injectable Anti-Coagulants 1. Indirect Thrombin Inhibitors 2. Direct Thrombin Inhibitors 1. Indirect Thrombin Inhibitors [Heparin] UFH Activate antithrombin Inhibit factor IIa = Xa LMWH Activate antithrombin Inhibit factor Xa > llaQ Fondaparinux Activate antithrombin Only inhibits factor XaQ Heparins 1. Route → S.C. or IV 2. Activate anti-thrombin 3. Immediate Action → Useful in acute conditions 4. Anti-coagulant of choice in pregnancy 5. Monitoring done by a PTT 6. Antidote → Protamine Sulphate WARFARIN HEPARIN Route Oral S/C or IV MOA Inhibit vitamin K Activate AT – III Onset 4-5 days Immediate Use Maintenance Acute condition Pregnancy C/I DOC Monitoring PT/INR aPTTQ Antidote Vitamin K Protamine 2. Direct Thrombin Inhibitors (DTI) • • Bivalirudin, argatroban and melagatran are injectable DTI.Q • • Hirudin and lepirudin are not used now • • These are DOC for heparin induced thrombocytopenia (HIT) ANTIDOTES OF ANTI-COAGULANTS Antidote Anticoagulant Vitamin K Protamine sulfate Idarucizumab Andexanet-Alpha Warfarin HeparinQ DabigatranQ Factor Xa inhibitors e.g., Apixaban FIBRINOLYTIC DRUGS • • All drugs in this group are tissue plasminogen activators. • • tPA converts plasminogen to plasmin that breaks the thrombus • • These are used for acute MI, acute stroke and acute DVT → Drugs S – Streptokinase U – Urokinase R – Reteplase A – Alteplase T – Tenecteplase Overdose of thrombolytics → Leads to bleeding → Antidotes: – – Epsilon Amino Caproic Acid [EACA] – – Tranexamic Acid. DRUGS AFFECTING BLOOD CELLS • • Hematinics • • Growth factors HEMATINICS These are nutritional substances which help in formation of blood. e.g. 1. Iron (Fe) 2. Folic acid (FA) 3. Vitamin B12 Iron Deficiency Anemia • • Treatment of choice is Oral iron. Oral Iron • • Various preparations like ferrous sulphate, ferrous fumarate are available. – – For adults, tablets are given – – For children drops are available. These should be given deep in mouth or else they cause skin pigmentation • • Earliest response - ReticulocytosisQ • • If Hb is improving by 0.5 g/dl/week, that means adequate response
Ad
62 Cerebellum Quick Revision Notes • • Oral iron treatment is continued for 2-3 months even after the Hb levels come to normal to replenish the iron stores in body. • • Factors affecting – – Ascorbic acid : Increase Absorption – – Phytates and oxalates :Decrease Absorption Injectable Iron • • Preparations of injectable iron are: – – Iron Dextran –Can be given IV as well as IM – – Iron Sorbital citrate (Used IM only) • • Intramuscular iron is given by Z-tract technique to avoid pigmentation HEMATOPOIETIC GROWTH FACTORS Cells Growth Factor Drug Indications RBC Erythropoietin Darbopoietin Anemia due to chronic renal failure Anemia due to bone marrow suppression WBC G-CSF GM-CSF Filgrastim Sargramostim Leukopenia due to bone marrow suppression Platelets IL-11 Oprelvekin Thrombocytopenia due to bone marrow suppression Previous Years Questions Q1. Which of the following is an oral direct thrombin inhibitor? A. Dabigatran B. Rivaroxaban C. Warfarin D. Lepirudin Q2. What is the mechanism of action of tPA? A. Fibrinolysis B. Inhibition of factor V and VII C. Inhibition of factor III and V D. Activation of anti-thrombin III Q3. A female patient was taking warfarin for prosthetic heart valves. She became pregnant. What advise will you give regarding use of this drug in early pregnancy? A. Continue warfarin without any concern B. Continue warfarin but add vitamin K to the therapy C. Change warfarin to heparin D. Terminate the pregnancy Q4. In the given diagram, identify drug Z marked by the arrow A. Clopidogrel B. Heparin C. Dicumarol D. Alteplase Q5. A patient presented to hospital with chest pain. ECG of the patient confirms it to be non ST elevation myocardial infarction. Which of the following drug useful in this patient acts by inhibiting platelet aggregation? A. Clopidogrel B.Streptokinase C. Low molecular weight heparin D.Warfarin Answers 1. - A 2. - A 3. - C 4. - C 5. - A
63 Pharmacology Drug A Drug B Drug C a Aspirin Vorapaxar Prasugrel b Dipyridamole Eptifibatide Vorapaxar c Aspirin Eptifibatide Prasugrel d Dipyridamole Prasugrel Eptifibatide Q10. Which of the following statements is most correct regarding mechanism of action of dicumarol? A. It acts as a calcium chelator and reduces the availability of calcium in coagulation pathway B. It binds and activates anti-thrombin 3 that accelerates its interaction with thrombin and factor Xa resulting in their degradation C. It acts as a Vitamin K inhibitor that results in inhibition of activation of clotting factors 2,7,9 and 10 D. It inhibits tissue plasminogen activator resulting in stoppage of conversion of plasminogen to plasmin Q11. Vitamin that increases the absorption of iron from stomach is? A. Vitamin A B. Vitamin B12 C. Vitamin C D. Vitamin D Q12. Excessive phytates intake in the diet may lead to deficiency of A. Proteins B. Iron C. Vitamin B12 D. Vitamin D Q13. Indication for use of Pegylated Filgrastim is in the correction of: A. Anaemia B. Neutropenia C. Thrombocytopenia D. Pancytopenia Q6. A deep vein thrombosis patient was started on an anticoagulant therapy. Next day, the patient presented with the features shown in the diagram below. Likely drug implicated for this adverse effect is A. Heparin B. Rivaroxaban C. Warfarin D. Dabigatran Q7. Among the following drugs, oral factor Xa inhibitor is: A. Dabigatran etexilate B. Rivaroxaban C. Fondaparinux D. Bivalirudin Q8. A 45 year old patient being treated with low dose aspirin since 6 months presented with rectal bleeding. Inhibition of which of the following substance is likely to responsible for the bleeding? A. TXA2 B. LT C. Bradykinin D. PGI2 Q9. Mechanism of action of some antiplatelet drugs is shown in the given diagram. Which of the following is correct match: Answers 6. - C 7. - B 8. - A 9. - C 10. - C 11. - C 12. - B 13. - B
Ad
Chapter - 9 Gastrointestinal Tract PEPTIC ULCER DISEASE → Due to excessive acid in stomach Treatment 1. ↓ ACID → HCl produced by Parietal cell of stomach → Proton Pump [H+ -K+ -Pump] helps in secretion of acid – – Stimulated by ƒ ƒ ACh [M1 ] ƒ ƒ Histamine [H2 ] ƒ ƒ Gastrin [CCK] – – Inhibited by PGE2 Drugs ↓ Acid M1 blockers H2 blockers PGE2 PPI Pirenzepine Telenzepine Cimetidine Ranitidine Famotidine Loxatidine Misoprostol Omeprazole Esomeprazole Pantoprazole Lansoprazole Rabeprazole Most specific drug for NSAID induced Peptic ulcer MisoprostolQ DOC for NSAID induced Peptic ulcer Proton Pump lnhibitorsQ PPls [Proton Pump Inhibitors] • • Irreversible inhibitors • • Example of Hit and Run Drugs • • Exert systemic effect [Do not work locally] • • Given with acid resistant coating (Enteric coating) Indications • DOC for PUD due to any reason • DOC for GERD • DOC for Zollinger Ellison Syndrome Adverse Effects (on long-term use) • • ↓ Ca2+ [Osteoporosis] • • ↓ Vit B12 [Megaloblastic anaemia]Q • • ↑ Infections 2. ANTACIDS → Fastest pain relievers of PUD → Include – – AI [OH]3 → Cause constipation – – Mg [OH]2 → Cause Diarrhoea → Given in combination 3. ULCER PROTECTIVE DRUGS → Sucralfate → Sucralfate acts by Polymerization, requires acidic pH [<4] – – Should not be combined with antacids → Inhibits absorption of several drugs like phenytoin. So, a gap of minimum 120 minutes should be kept between two drugs 4. ANTI-H. PYLORI DRUGS • Amoxycillin • Metronidazole • Clarithromycin Triple Drug Therapy • • Used for H. pylori associated PUD • • PPI + 2AMA used C → Clarithromycin A → Amoxycillin P → PPI Preferred triple drug therapyQ Given for 2 weeks
65 Pharmacology Previous Years Questions Q1. A patient on phenytoin for seizure disorder was prescribed sucralfate 4 times a day for peptic ulcer. What should be the minimum duration between consumption of two drugs? A. 30 min B. 60 min C. 90 min D. 120 min Q2. A female with ovarian cancer was on cisplatin therapy. He presented to hospital with several episodes of vomiting. After giving an antiemetic drug, the patient developed dystonia. The anti-emetic drug most likely to be responsible for these features is A. Metoclopramide B. Meclizine C. Ondansetron D. Scopolamine Q3. Which of the following is not a prokinetic? A. 5HT4 agonist B. D2 blocker C. Macrolides D. Diphenoxymethane Q4. A patient presented to hospital with three bouts of vomiting and treated with anti-emetic drug. Vomiting subsided but after sometime, he developed abnormal movements. Which of the following drug is used for treatment of these motor symptoms? A. Benzhexol B. Cyproheptadine C. L-dopa D. Hyoscine Q5. A patient is planned to receive chemotherapy with cisplatin. Which of the following drugs are used for the treatment of chemotherapy induced nausea and vomiting A. Granisetron, aprepitant and dexamethasone B. Metoclopramide, dexamethasone and domperidone C. Prochlorperazine, granisetron and domperidone D. Promethazine, doxylamine and metoclopramide Answers 1. - D 2. - A 3. - D 4. - A ANTI-EMETIC DRUGS 1. Chemotherapy induced nausea and vomiting (CINV): Type Drug of Choice Early CINV 5HT3 antagonistsQ - Ondansetron - Granisetron - Palonosetron Delayed CINV Substance P antagonistsQ - Aprepitant - Rolapitant 2. D2 Blockers Metoclopramide DomperidoneQ Cross BBB Do not cross BBB Can cause dystonia Do not cause dystonia DOC for Levodopa induced vomiting PROKINETIC DRUGS → Used in GERD → Drugs are 1. D2 Blockers • • Domperidone • • Metoclopramide 2. 5HT4 Agonist • • Mosapride • • Prucalopride 3. Motilin Receptor Agonist • • Erythromycin 5. - A
Ad
BRONCHIAL ASTHMA 1. Bronchodilators A. Sympathomimetics b2 Agonists Salmeterol → Slow acting → Only used for prophylaxis Formoterol → Fast acting → Used for acute attacks also Adverse Effects of b2 Agonists T - Tachycardia T - Tremors (Most common side effect) T - Tolerance (Mainly with long-acting beta 2 agonists) T - T wave changes (Because of hypokalaemia) These drugs can cause hyperglycaemia (but never hypoglycemia) B. Parasympatholytics M3 Blockers • • Ipratropium • • Tiotropium → Given by inhalational route C. Phosphodiesterase Inhibitors • • Include theophylline and aminophylline • • Given orally or by intravenous route (not available by inhalational route) Chapter - 10 Respiratory System Mechanism → Inhibit PDE (thereby ↑ cAMP) → Adenosine A1 receptor antagonistQ Adverse effects Due to PDE inhibition Due to ADEnosine A1 an- tagonismQ Nausea, Vomiting, Diarrhea Arrhythmias Headache Diuresis Arrhythmias Epileptic seizures → Theophylline is metabolized by microsomal enzymes, so prone to drug interactions • • Enzyme inducers (like smoking) decrease the effect, therefore smokers require higher doses • • Enzyme inhibitors (like ciprofloxacin, clarithromycin and erythromycin) can result in toxicity (seizures, arrhythmias etc.)Q 2.Drugs affecting LTs A. Steroids → DOC for prophylaxis → Also used in acute attack along with bronchodilators Function in acute attack of asthma is to ↑ the sensitivity of b2 agonists. → Preferred by inhalational route – – MC side effect is oropharyngeal candidiasis – – Topical Nystatin or clotrimazole is used to treat candidiasis – – Gargling after every dose will prevent this adverse effect
67 Pharmacology Previous Years Questions Q1. A patient was taking theophylline for bronchial asthma. After starting another drug, symptoms of theophylline toxicity started appearing. Which is the likely drug started? A. Erythromycin B. Phenytoin C. Griseofulvin D. Rifampicin B. LOX inhibitors – – Zileuton C. LT Receptor antagonists – – Zafirlukast – – Montelukast 3. Mast Cell Stabilizers – – Sodium Cromoglycate – – Nedocromil → Only used for prophylaxisQ → Given by inhalational route 4. Omalizumab → Monoclonal antibody against IgEQ → Only used for prophylaxis → Given subcutaneously GINA (GLOBAL INITIATIVE FOR ASTHMA) GUIDELINES • • Drug of choice for treatment of acute attack of asthma (rescue therapy) is combination of inhalational formoterol and low dose inhaled corticosteroids.Q • • Drug of choice for maintenance therapy in asthma is also the same combination (Formoterol + Low dose ICS).Q Q2. A patient with COPD was given intravenous aminophylline therapy following which the patient developed diuresis. This is due to action on which effector? A. Adenosine receptors B. Beta 2 adrenergic receptors C. IL-10 D. Histone deacetylase Answers 1. - A 2. - A
Ad
Chapter - 11 Antimicrobial Agents These drugs are used to kill or inhibit the growth of micro-organisms CLASSIFICATION OF ANTIMICROBIALS Based on activity CIDAL: These kill the microoganisms These must be used to treat infections in immunocompromised person BEta lactams VAncomycin Fluroquinolones Aminoglycosides BE VA F A STATIC: These inhibit the growth of microorganisms. These cannot be relied upon if there is immunosuppression Based on Mechanism of Action Cell wall inhibitors Firmly – Fosfomycin Bind to – Beta lactans Bacterial – Bacitracin Cell – Cycloserine Vall – Vancomycin Protein inhibitors Bind at 30S ribosomes: Aminoglycosides Tetracyclines Bind to 50S ribosomes: Chloramphenicol Macrolides Clindamycin Quinpristin Linezolide Metabolism inhibitors – Sulfonamides – Trimethoprim – Pyrimethamine DNA gyrase inhibitors – Fluroquinolones – Nalidixic acid Drugs acting on membranes – Daptomycin – Polymyxin B – Polymyxin E • • Vancomycin inhibits transglycosylase and thus chain elongation step in bacterial cell wall synthesis.Q • • Beta-lactams inhibit transpeptidase and thus cross- linking of peptidoglycan chainsQ CELL WALL SYNTHESIS INHIBITORS A. BETA LACTAMS 1. Penicillins 2. Cephalosporins 3. Carbapenems 4. Monobactams 1. Penicillins Penicillin G (Benzyl Penicillin) Limitations 1. Not effective orally [Acid labile] 2. Short acting [Due to rapid tubular secretion] 3. Narrow spectrum 4. Resistance 5. Allergy
69 Pharmacology 1. Acid Resistant / Oral Penicillins V → Penicillin V (Phenoxymethyl Penicillin) O → Oxacillin D → Dicloxacillin K → Cloxacillin A → Ampicillin, Amoxycillin 2. Prolong duration of action a. Probenecid competes with Penicillin for transporters in PT → ↑ Duration of action of Penicillin b. Depot Preparations • • Benzathine Penicillin G → Longest acting Penicillin • • Procaine Penicillin G – – Depot preparations are given by IM route only 3. Spectrum of Penicillins • • Mainly against gram positive bacteria. • • Not effective against most gram negative bacilli. Extended (Wide) Spectrum PenicillinsQ A → Ampicillin, Amoxycillin Ci → Carbenicillin Ty → Ticarcillin M → Mezlocillin A → Azlocillin P → Piperacillin – – All of these are effective against Pseudomonas except ampicillin and amoxycillin 4. Solving problem of resistance A. b Lactamase Inhibitors • • β-lactams break the structure of penicillin at β-lactam ring • • Clavulanic acid, sulbactam and tazobactam inhibit these enzymes and prevent resistance • • Combinations are: – – Clavulanic Acid + Amoxycillin – – Sulbactam +Ampicillin – – Tazobactam + Piperacillin B. Penicillinase Resistant Penicillins C → Cloxacillin O → Oxacillin N → Nafcillin D → Dicloxacillin O M → Methicillin [Most resistant] MRSA [Methicillin Resistant staph. aureus] - Resistance is due to altered Penicillin Binding Proteins - All β-lactams are ineffective except 5th gen cephalosporins 5. Allergy • • Skin testing done by intradermal injection of drug • • Cross Allergy → If allergic to one penicillin, all β lactams can cause allergy except monobactam Indications of Penicillins Penicillins are First Line Drugs inQ L → Listeria (DOC is ampicillin) A → Actinomycosis S → Syphilis T → Tetanus M → Meningococcus AN → Anthrax 2. Cephalosporins 1st Gen 2nd Gen 3rd Gen 4th Gen 5th Gen Cefazolin Cefalexin Cefadroxil Cefuroxime Cefoxitin Cefaclor Cefixime Cefotaxime Ceftizoxime Cefpodoxime Ceftazidime Cefoperazone Ceftriaxone Ceftibuten Cefepime Cefpirome Ceftibiprole Ceftaroline • • Cefazolin is DOC for surgical prophylaxis • • 5th generation are effective against MRSA A. Cephalosporins secreted in bile • • Safe in renal failure • • Include – – Cefoperazone – – Ceftriaxone
Ad
70 Cerebellum Quick Revision Notes Antimicrobial Agents That are Secreted in Bile Cef in --- Cefoperazone,Q Ceftriaxone The --- Tigecycline R --- Rifampicin E --- Erythromycin N --- Nafcillin A --- Ampicillin L --- Lincosamides [Clindamycin] Disease --- Doxycycline B. Anti-Pseudomonal Cephalosporins → Include: – – Cefepime – – Cefpirome – – Cefoperazone – – Ceftazidime [Most effective anti-Pseudomonal cephalosporin]Q C. Disulfiram Like Reaction → Should not be given with alcohol → Include: • • CefoperazoneQ • • Moxalactam D. Hypoprothrombinemia (↓ Prothrombin) → ↑ Bleeding tendency → ↑ Risk of bleeding with warfarin → Avoided in hemophilia patients → Include: • • Cefoperazone • • Moxalactam 3. Carbapenems Imipenem: • • Effective against Gram (+), Gram (-) and Anaerobes • • Always given with Cilastatin because if given alone it is broken down by dehydropeptidase enzyme in the Kidney • • Imipenem is a broad spectrum antibiotic, it is also effective against Pseudomonas. Side effect : Seizures Contraindication : Epileptic patientsQ Other Carbapenems: Meropenem Ertapenem Doripenem Faropenem 4. Monobactam Only drug in the group is AztreonamQ → Do not show cross allergy → Effective only against Gm -ve bacteria including Pseudomonas B. VANCOMYCIN → It is not effective orally [Not Absorbed] Adverse Effects: • • When given by IV route → releases Histamine - Red man syndromeQ • • Nephrotoxic • • Ototoxic Indications • • DOC for MRSA infections • • Can be used for Pseudomembranous Colitis (Now DOC is fidaxomicin) • • Not effective against PseudomonasQ DOC for MRSA : Vancomycin DOC for VRSA : Daptomycin DOC for VRSA pneumonia : Linezolide PSEUDOMEMBRANOUS COLITIS • • It is a type of superinfection • • MC bacteria involved: Clostridium difficile • • MC antimicrobials implicated are: – – 3rd Gen. Cephalosporins > Clindamycin > Ampi or Amoxycillin > FQQ Treatment: DOC : Fidaxomicin (Low chances of relapse)Q Alternative : Oral vancomycin, Metronidazole Monoclonal Ab against toxin : Bezlotoxumab Cilastatin not required Lesser risk of seizures
71 Pharmacology PROTEIN SYNTHESIS INHIBITORS → Drugs inhibit protein synthesis by binding to 30S or 50S → It is rememberred as buy AT - 30, SELL @ 50 – – Aminoglycosides and Tetracyclines bind at 30S ribosomes – – Rest all (streptogramins, Erythromycin group, Linizolid and Lincosamides) bind at 50S ribosomes Aminoglycosides Drugs – – Streptomycin – – Gentamicin – – Amikacin General Properties • • Not effective orally [Not absorbed] • • Active mainly on Gm -ve [Including Pseudomonas] • • Not effective on anaerobic bacteria • • Cidal drugs (Only protein synthesis inhibitors which are cidal) • • These are nephrotoxic, ototoxic and can cause neuromuscular blockade Tetracyclines - Demeclocycline - Doxycycline - Minocycline Adverse Effects K – Kidney Failure – All are C/I except Doxycycline A - Anti-anabolic P – Phototoxic I – Insipidus diabetes (Inhibit ADH release) L – Liver Failure C/I D – Dentition and Bone problems (C/I in pregnancy andchildren < 8 years)Q E – Not to be given after Expiry [Risk of FanconiSyndrome] V – Vestibular dysfunction Uses S – SIADH [Demeclocycline] R – Rickettsia [DOC] I – Granuloma lnguinale L – LGV A – Atypical pNeumonia [DOC – Macrolides] N K – Cholera [DOC] A – Luminal Amoebiasis [DOC For amoebiasis → Metronidazole] Resistance: • • Due to development of efflux pumps Streptogramins → Quinpristin + Dalfopristin → Can be used for VRSA Macrolides – – Erythromycin – – Clarithromycin – – Roxithromycin – – Azithromycin Indications DOC forQ C: Chancroid, Corynebacterium L: Legionella A: Atypical Pneumonia P: Pertussis Linezolide • • DOC for VRSA pneumoniaQ • • Now approved for TB also • • It is a static drug, so not reliable in immunocompromised patients Lincosamides (Clindamycin) • • Secreted in Bile, so safe in renal failure • • Causes Pseudo membranous colitis • • Used in anaerobic bacterial infections • • DOC for lung abcess and brain abscessQ
Ad
72 Cerebellum Quick Revision Notes ANTIMETABOLITES A. Sulfonamides/Sulfa Drugs – – Sulfadoxine – – Sulfasoxazole – – Sulfamethoxazole – – Sulfadiazine – – Dapsone Adverse Effects A – Aplastic anemia B - Bilirubin displacement → Cause Kernicterus in newbornQ C - Crystalluria R - Rash A – Acetylation S – SLE H – Hemolysis in G6PD deficiency • • Sulfonamides are structural analogs of PABA, which is essential for synthesis of folic acid. Therefore, sulfonamides are competitive inhibitors of FA synthase enzyme. • • In any infection, where pus is present, which usually contains PABA, Sulfonamides are unlikely to be effective. B. Combinations 1. Cotrimoxazole Trimethoprim (T) + Sulfamethoxazole (S) • • Ratio for best bactericidal activity → 1: 20 (T:S) • • Ratio in tablet to attain this ratio → 1: 5 (T:S) Cotrimoxazole is DOC For P → Pneumocystis jiroveci N → Nocardia B → Burkholderia cepacian 2. Sulfadoxine + Pyrimethamine • • Indicated in Parasitic infections → Malaria → Toxoplasmosis DNA GYRASE INHIBITORS • • DNA Gyrase - Introduces negative supercoils and helps in replication. • • DNA gyrase Inhibitors inhibit replication by preventing uncoiling. • • The drugs are fluoroquinolones Fluoroquinolones Drugs: • • Norfloxacin • • Ofloxacin • • Ciprofloxacin • • Levofloxacin • • Moxifloxacin General Properties • • Oral cidal drugs • • Wide spectrum [Effective against Gm + ve as well as Gm -ve] • • C/I in pregnancy and children (<18 yrs) [Cause cartilage and tendon damage]Q • • Induce seizures [Avoided in Epilepsy] • • C/I in Renal Failure ExceptionQ P – Pefloxacin M – Moxifloxacin T – Trovafloxacin Safe in renal failure Avoided in liver disease Not effective in UTI Respiratory FQQ O – Ofloxacin M – Moxifloxacin G – Gatifloxacin Levofloxacin [Isomer of Ofloxacin, Long acting] These are active against respiratory infections caused by • • Gm +ve bacteria • • Gm -ve bacteria • • Atypical bacteria • • Mycobaterium TB DRUGS NOT EFFECTIVE AGAINST PARTICULAR BACTERIA Bacteria Resistant to DOC 1. Mycoplasma Cell wall inhibitors Macrolides 2. MRSA Beta lactams Vancomycin 3. Pseudomonas Vancomycin Aminoglycoside + Ceftazidime 4. Enteric fever Aminoglycosides Ceftriaxone 5. Anaerobes Aminoglycosides Metronidazole
73 Pharmacology TUBERCULOSIS FIRST LINE DRUGS H → Isoniazid R → Rifampicin [RCIN] Z → Pyrazinamide E → Ethambutol S → Streptomycin (Not first line now) Activity Bacteria Hepatotoxic Pregnancy H Cidal Both √ Safe R Cidal Both √ Safe Z Cidal i/c √ √ √ Avoided E Static Both X Safe S Cidal e/c X C/I lsoniazid (INH) • • INH is activated by catalase peroxidase (formed by Kat G)Q enzyme of mycobacteria. It acts by inhibiting the formation of mycolic acid. • • Causes pyridoxine (Vitamin B6) deficiency resulting in peripheral neuropathy. So, pyridoxine is used for treatment as well as prevention • • Hepatotoxic (INH: lsoniazid causes Neuropathy and Hepatotoxicity)Q Rifampicin • • Act by inhibiting RNA polymerase of mycobacteria by binding to its β-subunit. It thus inhibits transcription. • • Should be given on empty stomach • • Secreted in Bile → Safe in renal failure • • Enzyme Inducer Interactions Warfarin Heparin OCP Other contraceptive method Replace with Replace with Other Uses: • • Leprosy • • Effective against Gram positive bacteria (including MRSA) • • Effective against Gram negative bacteria (including Pseudomonas) Other First Line Drugs • • Pyrazinamide causes gout • • Ethambutol causes red-green color blindness (optic neuritis) SECOND LINE DRUGS A. Cidal Drugs 1. FQ • • Ofloxacin • • Moxifloxacin • • Gatifloxacin • • Levofloxacin 2. Injectable • • Capreomycin • • Kanamycin • • Amikacin • • Streptomycin B. Drugs used for other conditions, now approved for TB 1. Linezolide – Also used for VRSA 2. Clofazimine – Also used for multibacillary leprosy C. Other static drugs: 1. Cycloserine – Causes neuropsychiatric adverse effects 2. Ethionamide – Hepatotoxic 3. PAS – Causes hypothyroidism 4. Thioacetazone – Never given in HIV patients D. New drugs: 1. Bedaquiline 2. Delamanid 3. Pretomanid TREATMENT OF TUBERCULOSIS (NTEP) Drug Sensitive TB: 2HRZE + 4 HRE
Ad
74 Cerebellum Quick Revision Notes Drug Resistant TB Multi drug (MDR) Resistant to H+R Rifampicin resistance Resistant to R but sensitive to H Pre-XDR Resistant to H + R + FQ Extensive (XDR) Resistant to H + R + FQ + One of Bedaquiline or Linezolide For TB with HIV – – First start treatment of TB (ATT) – – After 2 weeks, start treatment of HIV (ART) LEPROSY Rifampicin 600 mg Once monthly Supervised Clofazimine 300 mg Once monthly Supervised Clofazimine 50 mg Once daily for 28 days Unsupervised Dapsone 100 mg Once daily for 28 days Unsupervised Above regimen is given for – 12 months in multi-bacillary leprosy – 6 months in pauci-bacillary leprosy Lepra Reactions – – DOC for both type 1 and type 2 Lepra reaction is steroids – – MDT for leprosy should continueQ ANTI-HIV DRUGS 1. Fusion Inhibitors Enfuvirtide Maraviroc • Binds with GP 41 of Envelope and Fusion of Virus with T cell is Inhibited • Given subcutaneously • Binds with CCR-5 • Given orally 2. Reverse Transcriptase Inhibitors(RTI) → Inhibit reverse transcriptase (RNA dependent DNA polymerase) → May be competitive (NRTI) or Non-competitive (NNRTI) A. Competitive RTI NRTI (Nucleotide or side RT inhibitors) Nucleoside RTI Nucleotide RTI Zidovudine Lamivudine Stavudine Didanosine Zalcitabine Emtricitabine Abacavir Tenofovir
75 Pharmacology NRTI Adverse Effect Zidovudine Abacavir Zalcitabine Emtricitabine Didanosine Stavudine Bone Marrow SuppressionQ MI Aphthous ulcers in mouth Pigmentation of palms and soles Maximum risk of pancreatitis Maximum risk of peripheral neuropa- thy B. Non-Competitive RTI (NNRTI) – – Efavirenz – – Nevirapine – – Delavirdine 3. Integrase Inhibitors → Can be given orally → One of the first line drugs for HIV now.Q → Drugs include – – Raltegravir – – Elvitegravir – – Dolutegravir 4. Protease Inhibitors • • Ritonavir • • Lopinavir • • Amprenavir • • Fosamprenavir • • Atazanavir • • Saquinavir • • Nelfinavir • • lndinavir Properties of Protease Inhibitors • • Substrates of CYP3A4 • • Inhibitors of CYP 3A4 – – Strongest is ritonavirQ – – Boosts the effect of other protease inhibitors • • Cause lipodystrophy syndrome – – ↑ Glucose – – ↑ Lipids – – Insulin resistance – – Weight gain CLINICAL MANAGEMENT OF HIV 1. Treatment of HIV • • Called HAART (Highly Active Anti Retro Viral Therapy) • • Should be given to All HIV positive patients irrespective of CD4 count • • Given for life long duration • • Minimum 3 drugs (from minimum 2 groups) should be used • • First line therapy is – – 2 NRTI +1 NNRT/ integrase Inhibitors – – Commonly used – T + L + E or T + L + DQ [T – Tenofovir, L – Lamivudine, E – Efavirenz, D – Dolutegravir] 2. Post exposure prophylaxis → To prevent development of HIV after exposure → Used commonly in health care workers → Should be started as early as possible after exposure (within maximum limit of 72 hours) → Should be given for 28 days (4 weeks)Q → All the drugs are given orally → Drugs: Tenofovir +Lamivudine + ProteaseQ Inhibitors (or integrase inhibitors) ANTI-INFLUENZA DRUGS Uncoating Inhibitors Neuraminidase inhibitors Amantadine Rimantadine Inhibit release of virus from cell • • Oseltamivir - Oral • • Zanamivir - Inhalation • • Peramivir - Parenteral D.O.C for Bird flu (H5N1) and Swine flu (H1N1) ANTI-HERPES VIRUS DRUGS • • HSV-1 • • Mucocutaneous Herpes and Herpes Encephalitis • • HSV-2 • • Genital Herpes • • VZV • • Chicken pox • • DOC for all of them is ACYCLOVIR • • Ganciclovir is DOC for CMV.
Ad
76 Cerebellum Quick Revision Notes ANTI-HEPATITIS VIRUS DRUGS Hepatitis B L : Lamivudine E : Emtricitabine T : Tenofovir (DOC) Hepatitis C → Previously treated with interferon and ribavirin → Treatment was very toxic → Now all oral treatment is used New Oral Drugs for Hepatitis C Protease Inhibitors NS 5A Inhibitors NS 5B Inhibitors Previrs Asvirs Buvirs Telaprevir Elbasvir Sofosbuvir Simprevir Ledipasvir Dasabuvir Boceprevir Daclatasvir Beclabuvir Grazoprevir Ombitasvir Paritaprevir Pimbrentasvir DRUGS FOR COVID-19 • • Caused by Novel corona virus • • Most cases are self-limiting Important drugs 1. Steroids • • Only life saving drugs in COVID-19 pneumonia. • • Safe in children • • Increase the risk of infections like mucormycosis 2. Remdesivir • • Inhibit RNA dependent RNA polymerase.Q • • Given intravenously. • • Effective in first 10 days of illness only. • • Given with steroids (or baricitinib). • • Only US-FDA approved drug for COVID-19 pneumonia. 3. Monoclonal antibodies against spike protein • • Drugs include Bebtelovimab • • Indicated for OPD treatment • • Decrease risk of hospitalization. ANTIFUNGAL DRUGS 1. TOPICAL ANTIFUNGAL DRUGS: → Used for dermatopytosis e.g. azoles → Used for steroid induced oropharyngeal candidiasis e.g. nystatin, clotrimazole Drugs: C : Ciclipirox olamine A : Azoles, Amorolofine T : Terbinafine Sertaconazole (Has anti-inflammatory and anti-pruritic activity) 2. SYSTEMIC ANTIFUGAL DRUGS DRUG MECHANISM USE Azoles Inhibit lanosterol 14-a- demethylase DOC for Candidasis is fluconazole DOC for Aspergillosis is voriconazoleQ Amphotericin -B Bind to ergosterol and create pores Mucormycosis (DOC) Cryptococcal meningitis (DOC) Kala azar (DOC) Terbinafine Inhibit squalene epoxidase Dermatophytosis (DOC) Griseofulvin Inhibit mitotic spindle Dermatophytosis 5-Flucytosine Inhibit DNA Polymerase With AMB for cryptococcal meningitis Caspofungin Cell wall inhibitorQ Candidasis Aspergillosis Note: AMB is nephrotoxic but Liposomal AMB is less nephrotoxic
77 Pharmacology ANTI-PARASITIC DRUGS MALARIA • • Caused by Plamodium • • Transmitted by female Anopheles Treatment of Malaria Type of Malaria DOC DOC in 1st Trimester P. vivax malaria Chloroquine Chloroquine P falciparum malaria ACT Quinine Complicated or severe or cerebral Malaria IV Artesunate IV Artesunate Artemisinin Combination Therapy [ACT] • • Artemisinin + Long acting drug • • DOC for chloroquine resistant malaria • • Given orally • • Lumefantrine + Artemether: DOC in North Eastern States • • Artesunate + Sulfadoxine - Pyrimethamine: DOC for rest of India Radical Cure • • For P.vivax Malaria • • DOC is primaquine • • Given for 14 days • • C/I in G-6-PD deficiency, pregnancy and infants • • Tafenoquine is single dose radial cure of P.vivax malaria AMOEBIASIS Drug of Choice Luminal amoebiasis (Carrier state) Diloxanide Furoate (or Paromomycin)Q Intestinal and Hepatic amoebiasis Nitroimidazole (Nidazole) e.g. Metronidazole, Tinidazole, Secnidazole, Ornidazole, Satranidazole *Nidazoles can cause disulfiram like reaction, so are C/I in alcoholics USES OF METRONIDAZOLE:Q G - Giardiasis, Gardnerella vaginalis (bacterial vaginosis) U - Ulcer (Peptic ulcer) P - Pseudomembranous colitis T - Trichomoniasis A - Amoebiasis, Anaerobic bacterial infections
Ad
78 Cerebellum Quick Revision Notes Answers 1. - D 2. - A 3. - A 4. - A 5. - C Previous Years Questions Q1. The given diagram shows the steps in formation of bacterial cell wall. Identify the site of action of beta lactam antimicrobials: Q2. Which of the following cephalosporins can increase the effect of warfarin resulting in raised INR and increased risk of bleeding? A. Cefoperazone B. Cefixime C. Ceftibiprole D. Ceftazidime Q3. Carbapenem with maximum seizure risk is: A. Imipenem B. Meropenem C. Ertapenem D. Doripenem Q4. Cilastatin is given in combination with Imipenem because: A. Cilastatin prevents degradation of Imipenem in kidney B. Cilastatin increases absorption of Imipenem C. Inhibits the enzymes that digest Imipenem in stomach D. Reduces side effects of Imipenem. Q5. Mechanism of resistance to penicillins via beta lactamase is A. Altered penicillin binding proteins B. Drug efflux C. Breaks drug structure D. Alteration in 50S ribosome structure
79 Pharmacology Answers 6. - C 7. - C 8. - A 9. - B 10. - C 11. - A 12. - B 13. - B 14. - B 15. - A 16. - A 17. - B Q6. A patient presented with hospital acquired pneumonia. On testing he was found to be allergic to penicillin G. Which of the following drug is likely to be safe in this patient? A. Ceftriaxone B. Ampicillin C. Aztreonam D. Imipenem Q7. Mechanism of action of doxycycline is A. DNA gyrase inhibitor B. Cell wall synthesis inhibitor C. Protein synthesis inhibitor D. DNA dependent RNA polymerase inhibitor Q8. Drug of choice for Legionnaire’s disease is: A. Azithromycin B. Tigecycline C. Streptomycin D. Amoxycillin Q9. Which of the following antimicrobials is contraindicated in a patient with seizure disorder? A. Ampicillin B. Ofloxacin C. Doxycycline D. Cefixime Q10. A pregnant female with urinary tract infection took antimicrobials for the same. The baby of this female developed tendon rupture and arthropathy. What is the likely mechanism of action of the antimicrobial consumed by the pregnant female? A. Folic acid synthesis inhibitor B. Mycolic acid synthesis inhibitor C. DNA gyrase inhibitor D. DNA inhibitor Q11. Drug of choice for prophylaxis against Diphtheria is A. Erythromycin B. Rifampicin C. Cloxacillin D. Ciprofloxacin Q12. Fluoroquinolone contraindicated in liver disease is A. Levofloxain B. Pefloxacin C. Ofloxacin D. Lomefloxacin Q13. Which of the following is a second line anti- tubercular drug? A. Rifampicin B. Ethionamide C. Vancomycin D. Acyclovir Q14. All of the following are bactericidal drugs against Mycobacterium except A. Kanamycin B. Thioacetazone C. Rifapentine D. Isoniazid Q15. Which of the following drug will you omit from the prescription of a patient with XDR tuberculosis in pregnancy? A. Kanamycin B. Ethambutol C. Moxifloxacin D. Amoxycillin-clavulanic acid Q16. From the given diagram, identify the mechanism of action of isoniazid. A. Drug A B. Drug B C. Drug C D. Drug D Q17. A 48 year old patient presented to OPD with tingling and numbness of fingers. The patient is chronic alcoholic and was recently started on antitubercular treatment. What should be the treatment of this patient? A. Vitamin B3 B. Vitamin B6 C. Vitamin B1 D. Vitamin B12
Ad
80 Cerebellum Quick Revision Notes Answers 18. - B 19. - A 20. - C 21. - D 22. - C 23. - A 24. - B 25. - A 26. - A 27. - C Q18. In MDR tuberculosis, which of following drug combinations show resistance? A. Rifampicin and Fluoroquinolones B. Isoniazid and rifampicin C. Isoniazid and Pyrazinamide D. Rifampicin and kanamycin Q19. Which of the following drug acts by inhibiting the transcription of DNA to RNA? A. Rifampicin B. Nitrofurantoin C. Ciprofloxacin D. Novobiocin Q20. A female taking oral contraceptives acquired tuberculosis. After prescribing anti-tubercular therapy, physician advised the patient for alternative contraception. What is the probable reason of this advise? A. Rifampicin causes teratogenicity B. Isoniazid is teratogenic C. Rifampicinincreasesthemetabolismoforalcontraceptives D. Oral contraceptives decrease the efficacy of ATT Q21. A patient of borderline leprosy received multi drug therapy. He developed skin lesions as shown in the figure below. How should this patient be managed? A. Stop MDT and give thalidomide B. Continue MDT and give thalidomide C. Stop MDT and give steroids D. Continue MDT and give steroids Q22. A patient developed COVID-19 pneumonia and was treated. Few months later, patient presented with nasal congestion and swelling of face. There were black lesions on the nose bridge. A diagnosis of mucormycosis was made. What is the drug of choice for this condition? A. Fluconazole B. Dexamethasone C. Amphotericin B D. Azithromycin Q23. Mechanism of action of Triazoles anti-fungal drugs is: A. Inhibits ergosterol biosynthesis B. Inhibits tubulin C. Inhibits glucan synthesis D. Inhibits cell wall synthesis Q24. Drug of choice for invasive aspergillosis is A. Posaconazole B. Voriconazole C. Liposomal AMB D. Caspofungin Q25. An HIV patient presents with seizures and neck rigidity. The CSF examination shows the presence of organisms on India ink and a diagnosis of cryptococcal meningitis is made. Which of the following anti-fungal drug is used for initial treatment of this meningitis? A. Liposomal amphotericin B B. High dose fluconazole C. Fluconazole + 5 Flucytosine D. Voriconazole Q26. Which of the following drugs can be used for the treatment of severe covid-19 pneumonia in children? A. Steroids B. Remdesivir C. Ivermectin D. All of these Q27. A newly diagnosed tuberculosis patients was found to be HIV positive. Which of the following statement is true about treatment of this patient? A. Start ATT and ART together B. ARTshouldbestartedonlyifCD4countislessthan50/mcL C. ATTshouldbestartedfirstfollowedbyART2weekslater D. ARTshouldbestartedfirstfollowedbyATT2weekslater
81 Pharmacology Answers 28. - A 29. - A 30. - D 31. - A 32. - A 33 - B 34. - B 35. - A 36. - B 37. - A 38. - A Q28. Which of the following drugs improves bioavailability and prolongs duration of action of Saquinavir? A. Ritonavir B. Cimetidine C. Vitamin C D. Remdesivir Q29. Mechanism of action of Remdesivir is inhibition of? A. RNA dependent RNA polymerase B. DNA dependent RNA polymerase C. Viral protease enzyme D. Cell wall synthesis Q30. Mechanism of action of Oseltamivir is A. DNA polymerase inhibition B. Inhibition of viral mRNA C. Blocking viral uncoating D. Neuraminidase inhibition Q31. Which of the following drug is associated with causation of pigmentation of hand and soles on chronic use? A. Emtricitabine B. Nevirapine C. Zidovudine D. Abacavir Q32. A lady has taken medication of ameiobiasis infection . In a party she drank alcohol. She has nausea vomiting and dizziness . Which anti-amoebic drug could have lead to interaction with alcohol to produce these symptoms? A. Metronidazole B. Nitazoxanide C. Paromomycin D. Diloxanide Q33. A female patient presented with greenish vaginal discharge. Clue cells were present and Whiff test was positive in vaginal discharge. What is the drug of choice for this condition? A. Doxycycline B. Metronidazole C. Ceftriaxone D. Fluconazole Q34. A 30 year old man travelled to Assam. After coming back he developed fever, chills and rigors and altered sensorium. The peripheral smear demonstrated the presence of P. falciparum. What is the treatment of choice for this patient? A. Chloroquine, Sulfadoxine pyrimethamine B. Intravenous Artesunate C. Quinine D. Primaquine Q35. A 25 year old male has frequent visits to rural areas and need to eat outside food. During one such visit, he developed loose stools. Which of the following drug should be used to manage this case? A. Metronidazole B. Diphenoxylate C. Loperamide D. Octreotide Q36. A female patient presented with greenish vaginal discharge and pruritus. On colposcopy, strawberry cervix is noted. What is the drug of choice for this condition? A. Ceftriaxone B. Metronidazole C. Acyclovir D. Fluconazole Q37. The drug kit shown in the diagram below is used for the treatment of A. Malaria B. Kala azar C. HIV D. Syphilis Q38. Which of the following drug has highest risk of causing hemolysis in a patient with deficiency of Glucose-6-Phosphate Dehydrogenase enzyme? A. Primaquine B. Chloroquine C. Azithromycin D. Pyrimethamine
Ad
Anticancer drugs can be divided into a. Cytotoxic b. Targeted CYTOTOXIC DRUGS Common Adverse Effects • • BM Suppression • • Alopecia • • Mucositis → Diarrhea • • Hyperuricemia • • Nausea and vomiting (CINV) 1. Alkylating Agents Drugs: If – lfosfamide Bus – Busulfan Not – Nitrosoureas • Carmustine (BCNU) • Lomustine (CCNU) • Semustine (Methyl CCNU) Present – Procarbazine Take – Temozolomide My – Melphalan, Mitomycin C Cycle – Cyclophosphamide Important Points Regarding Alkylating Agents Cyclophosphamide Cause Hemorrhagic cystitisQ Cause Pulmonary fibrosis Ifosfamide Cause Hemorrhagic cystitis Busulfan Cause pulmonary fibrosis Nitrosoureas Cause Delayed neutropenia Procarbazine Cause disulfiram-like reaction Temozolomide DOC for gliomas Melphalan Used for multiple myeloma Mitomycin-C Used topically for *Subglottic stenosisQ *Superficial bladder cancer Chapter - 12 Anti-Cancer Drugs Hemorrhagic cystitis • • Caused by cyclophosphamide and ifosmide. • • Metabolite responsible is acrolein • • Prevented by mesnaQ • • Treatment is steroids. CYCLOphosphamide : CARmustine : BUSulphan : MethoTRUCKsate : (Methotrexate) AmioDaRONE : BLEOmycin : Drugs Causing Pulmonary FibrosisQ 2. Antimetabolites • • These are S Phase Specific a. Drugs affecting Folic Acid Metabolism • • Example: Methotrexate • • Act by inhibiting dihydrofolate reductase enzyme. Uses of Methotrexate: • • Choriocarcinoma - D.O.C • • Rheumatoid arthritis - D.O.C – – Methotrexate toxicity treatment- Folinic acid (Leucovorin or Citrovorum) b. Drugs Affecting Purine Metabolism 6-Mercaptopurine Hepatotoxic 6 - Thioguanine Hepatotoxic Cladribine DOC for Hairy cell LeukamiaQ Fludarabine DOC for CLLQ
83 Pharmacology c. Drugs Affecting Pyrimidine Metabolism 5-Fluorouracil [5-FU] Cause Hand and foot syndrome Capecitabine Proding Gemcitabine DOC for Pancreatic carcinoma Cytarabine Cause cerebellar side effects 3. Drugs Acting on Mitotic Spindle → Specific for M-Phase of cell cycle Formation inhibitors Breakdown inhibitors Vincristine Vinblastine PaclitaxelQ S/E → Peripheral neuropathy SIADH Vincristine → Marrow sparing anticancer drug 4. Topoisomerase Inhibitors Topoisomerase I inhibitors Topoisomerase II inhibitors Irinotecan → Used for colorectal carcinoma → Cholinergic Side effects Etoposide Anthracyclines • • Doxorubicin • • Donorubicin • • Epirubicin Anthracyclines – Cause Cardiotoxicity 5. Miscellaneous Drugs a. Bleomycin • • Marrow sparing • • Cause pulmonary fibrosis • • Causes Flagellated pigmentation of skinQ b. L-Asparaginase • • Marrow sparing • • Used for ALL • • Cause Allergy • • Cause Acute PancreatitisQ TARGETED ANTICANCER DRUGS A. SMALL MOLECULES 1. Tyrosine Kinase Inhibitors DOC for Chronic Myeloid Leukemia – Imatinib General Properties 1. All end with ‘nib’ 2. Orally effective Important Tyrosine Kinase Inhibitors For CMLQ I - Imatinib [DOC] N - Nilotinib D - Dasatinib • • Imatinib is DOC for CML and GIST • • Sorafenib is DOC for hepatocellular carcinoma • • Lapatinib is used for breast cancerQ
Ad
84 Cerebellum Quick Revision Notes B. MONOCLONAL ANTIBODIES → End with ‘MAB’ → Injectable Anticancer Drugs EGFR ANTAGONISTS: • • Cetuximab: Colorectal carcinoma • • Panitumumab: Colorectal carcinoma MAB AGAINST HER – 2 • • Trastuzumab • • Pertuzumab MAB AGAINST CD20 • • Rituximab : For Non-Hodgkin Lymphoma and CLL • Used for breast cancer • Cardiotoxic IMMUNE CHECK POINT INHIBITORS • • Normally, T-cells are not activated against normal cells because an interaction between PD-1 (receptor present on T-cells) and PDL-1 (Ligand present on normal cells) inhibit T-cells. This is called immune check point. Tumor cells do not express PDL-1 and thus can be killed by T-cells. • • Some tumor cells start expressing PDL-1 on their surface and thus can evade immunity by inhibiting T-cells. • • Immune check point inhibitors are monoclonal antibodies against PD-1 or PDL-1 to stop this interaction. T-cells now can kill cancer cells. • • These drugs can result in auto-immune conditions like autoimmune hepatitis as adverse effects. Drugs: Mnemonic DrugQ Use New Drugs Act At Immune Check Point Nivolumab Durvalumab Avelumab Atezolizumab Ipilimumab Cemiplimab Pembrolizumab HL, NSCLC Multiple cancers including endometrial cancer IMMUNOSUPPRESSANTS 1. STEROIDS 2. DRUGS TARGETING THE CALCINEURIN PATHWAY a. Cyclosprine and Tacrolimus b. Daclizumab and Basiliximab c. Sirolimus a. Cyclosporine and TacrolimusQ • • Inhibit formation of IL-2 b. Sirolimus and Everolimus • • Inhibit action of IL - 2 3. BIOLOGICAL AGENTS Formed by recombinant DNA technology TNF-α inhibitors A – Adalimumab C – Certolizumab E – Etanercept INhibitor – INfliximab GOLI – GOLImumab
85 Pharmacology Previous Years Questions Q1. Drug of choice for treatment of hairy cell leukemia is? A. Interferon alpha B. Fludarabine C. Pentostatin D. Cladribine Q2. Which of the following drug can cause the side- effect given in the picture? A. Bleomycin B. Mitomycin C C. Doxorubicin D. Actinomycin D Q3. A 50 year old female presented to oncologist with breast lump. On examination and investigations, breast cancer was diagnosed. Echocardiography of the patient shows ejection fraction of 25 %. Which of the following drug will you avoid in this patient? A. Epirubicin B. Irinotecan C. Cyclophosphamide D. Methotrexate Q4. A 20 year old boy presented with slow growing mass on the medial side of thigh. Investigations revealed it to be osteosarcoma and patient was started on methotrexate. Mechanism of action of methotrexate as an anticancer drug is A. Inhibition of Dihydrofolate reductase B. Inhibition of N5 tetrahydro folate reductase C. Inhibition of tyrosine kinase D. Inhibition of purine metabolism Q5. Topical application of 400 mcg/ml mitomycin C is used for A. Subglottic stenosis B. Tympanoplasty C. Rhinocerebral mucormycosis D. Nasopharyngeal bleeding Q6. Which of the following is not an immune check point inhibitor? A. Cetuximab B. Pembrolizumab C. Atezolizumab D. Nivolumab Q7. Which of the following is true about Rituximab A. Anti- CD 20, monoclonal antibody B. Anti-CD 50, monoclonal antibody C. Anti-CD 20 polyclonal antibody D. Anti-CD 50 polyclonal antibody Q8. What is mechanism of action of Cyclosporine? A. Calcineurin inhibitor B. mTOR inhibitor C. IL-2 receptor antagonist D. TNF-α inhibitor Answers 1. - D 2. - A 3. - A 4. - A 5. - A 6. - A 7. - A 8. - A
Ad
LOCAL ANAESTHETIC AGENTS Drugs Ester Amide Cocaine Lignocaine Procaine Bupivacaine Chlorprocaine Prilocaine Tetracaine Etidocaine Benzocaine Ropivacaine Dibucaine Special points: • • Only LA causing vasoconstriction CocaineQ • • MC used LA Lignocaine • • Shortest acting LA Chlorpropane • • LA causing methemoglobinemia PrilocaineQ • • Maximum Cardiotoxic BupivacaineQ Local Anaesthetic Systemic Toxicity (LAST): → Characterized by – – Arrhythmias – – Cardiovascular collapse – – Seizures → Treatment is – – Cardiopulmonary resuscitation – – 20% intralipid (DOC)Q SKELETAL MUSCLE RELAXANTS NEUROMUSCULAR BLOCKERS: These may be depolarizing or non-depolarizing skeletal muscle relaxants Depolarizing Muscle Relaxants (DMR) Non Depolarizing Muscle Relaxants (NDMR) • • Act by blocking NM receptors competitively • • Example is d-Tubocurarine (Curare) • • It does not cause post opeartive muscle pain • • Release Histamine that causes bronchoconstriction and hypotensionQ Other NDMR Curium [Release less histamine] Curonium [No histamine released] Atracurium Cis-Atracurium Mivacurium [Shortest acting] Pancuronium Pipecuronium Vecuronium Rocuronium Rapacuronium • • Cis-atracurium release less histamine than atracurismQ Hoffman’s Elimination • • Shown by Atracurium and Cis-atracurium • • Muscle relaxant of choice in liver and renal diseaseQ Reversal Agents Used to reverse action of NDMR after surgery → Neostigmine: Can cause cholinergic adverse effects → Suggamadex: No cholinergic side effectsQ GENERAL ANAESTHETICS INDUCING AGENTS (INTRAVENOUS) • • Thiopentone • • Ketamine • • Propofol • • Etomidate Thiopentone • • Highly lipid soluble • • Very short acting d/t Redistribution Chapter - 13 Anaesthesia • • Acts by stimulating NM receptors • • Example is Succinylcholine (SCh)Q Succinylcholine (SCh) • • Shortest acting MR [< 5 min] • • C/I in nerve and muscle injuries [Can cause severe hyperkalemia] • • Hyperthermia [precipitate malignant hyperthermia] • • Fasciculations: Responsible for post operative muscle pain
87 Pharmacology Propofol • • Painful • • DOC for day care SurgeryQ • • Avoided in patients with egg allergy Etomidate • • Agent of choice for CVS surgery • • Causes Adrenal SuppressionQ Ketamine K → Agent of choice in kids E → Emergence Rxn (post operative delirium and hallucinations) T → Thalamo- Cortical junction (site of action) Dissociative AnesthesiaQ A → Analgesic M → Meals (can be given in full stomach) I → ↑ BP/IOP/ ICP (Agent of choice in shock) N → NMDA Blocker E → Excellent bronchodilatorQ INHALATIONAL AGENTS N2O Highest MAC (104%)Q Halothane Causes hepatitis Causes malignant hyperthermia Enflurane Seizures (Maximum risk) Isoflurane DOC for cardiovascular and neurosurgery Sevoflurane DOC for children Methoxyflurane NephrotoxicQ Desflurane Maximum irritation to respiratory pathway Xenon Ideal anaesthetic agent 1. MAC (Minimum Alveolar concentration) • • Minimum Concentration required in alveoli to produce anaesthesia Mac a 1 Potency MAC Potency Drug Maximum Minimum Least Most N2O (104%) Methoxyflurane 2. Blood Solubility Measured by blood gas partition coefficient (BGPC)Q BPGC a 1 speed of onset BGPC Onset Drug Highest Slowest Methoxyflurane Lowest Fastest Xenon COLORS OF CYLINDERS N2 O Blue (NEELA) Cyclopropane Orange (SANTRI) O2 Black and white (Black body and White shoulder) Entonox – – Blue and White (Blue body and White shoulder) – – Mixture of 50% N2 O and 50% O2 is Entonox
Ad
88 Cerebellum Quick Revision Notes Previous Years Questions Q1. Mechanism of action of curare like drugs is A. Competitive, Non depolarizing block at the Nm cholinergic receptors B. Non-competitive, Non depolarizing block at the Nm cholinergic receptors C. Competitive, Depolarizing block at the Nm cholin- ergic receptors D. Non-competitive, Depolarizing block at the Nm cholinergic receptors Q2. Reason for preferring cis-Atracurium over Atracurium is: A. Equal potency like Atracurium B. Lesser provocation of histamine release C. Short fast action D. Does not undergo Hoffman elimination Q3. A person was given a muscle relaxant that competitively blocks nicotinic receptors. Which of the following drug is used for reversal of muscle relaxation after surgery? A. Neostigmine B. Carbachol C. Succinylcholine D. Physostigmine Q4. An anesthetist injected bupivacaine in a patient for axillary nerve block. Later, the patient developed restlessness, agitation and cardiovascular collapse. Next best step in the management would be? A. Cardiac resuscitation + dopamine B. Cardiac resuscitation + dantrolene C. Cardiac resuscitation + sodium bicarbonate D. Cardiac resuscitation + 20 % intralipid Q5. A patient was admitted for surgery and halothane is being planned to be used as an anaesthetic agent. The patient was explained about the adverse effect of malignant hyperthermia with this drug. Which of the following drugs may also result in malignant hyperthermia? A. Succinylcholine B. D-Tubocurarine C. Dantrolene D. Baclofen Q6. Which of the following drug is associated with post operative delirium and hallucinations? A. Ketamine B. Thiopentone C. Fentanyl D. Halothane Q7. Inhalational anesthetic agent with highest respiratory irritation is: A. Desflurane B. Nitrous Oxide C. Sevoflurane D. Halothane Q8. Which IV anesthetic does not cause cardiac depression? A. Etomidate B. Propofol C. Methohexitone D. Thiopentone Q9. Inhalational anaesthetic agent of choice in children is A. Isoflurane B. Desflurane C. Sevoflurane D. Halothane Q10. A patient of COVID-19 requires oxygen therapy. Which of the following cylinders should be used to provide oxygen to this patient? A B C D Answers 1. - A 2. - B 3. - A 4. - D 5. - A 6. - A 7. - A 8. - A 9. - C 10. - A
ANTI-SMOKING DRUGS 1. Nicotine Replacement Therapy (NRT) • • Most commonly used anti-smoking drugs • • Available as chewing gums and lozenges • • Lozenges have more bioavailabilty than gums • • Do not take tea or coffee for 15 minutes after taking NRT 2. BupropionQ • • Bupropion is anti-smoking whereas buspirone is anti-anxiety 3. VarenicilineQ • • Most effective anti-smoking drug • • Can cause CVS and CNS adverse effects ANTI-OBESITY DRUGS O – Orlistat B – Bupropion + Naltrexone E – Exenatide S – Semaglutide I – LIraglutide Ty – Tirzepatide Topiramate + Phentermine • • Orlistat is oral lipase inhibitor. It inhibits absorption of fats. Major adverse effect is steatorrhea.Q • • GLP-1 analogues include exenatide, liraglutide and semaglutide • • Tirzepatide is dual GLP-1 and GIP agonist. ANTIDOTES Poisoning Antidote Beta blocker GlucagonQ Organophosphate Atropine Opioid NaloxoneQ Methanol FomepizoleQ Ethylene glycol Fomepizole Warfarin Vitamin K Chapter - 14 Miscellaneous Topics Heparin Protamine sulfate Paracetamol N. AcetylcysteineQ Atropine Physostigmine Iron Desferrioxamine Benzodiazepine FlumazenilQ Zolpidem Flumazenil Cyanide Hydroxocobalamin (or Amyl nitrite)Q Valproate hepatotoxicity L-carnitine MANAGEMENT OF HYPERKALEMIA Acute hyperkalemiaQ 1. Drugs increasing intracellular movement of K+ • • Glucose - Insulin (DOC) • • Beta 2 agonists e.g. salbutamol, epinephrine 2. Drugs reversing ECG changes • • Calcium gluconate Chronic Hyperkalemia • • Long - term oral treatment • • Drugs used: – – Patiromer ERECTILE DYSFUNCTION • • DOC: PDE-5 inhibitor – – Sildenafil – – Tadalafil (Longest acting)
Ad
90 Cerebellum Quick Revision Notes CHELATING AGENTS • • Used for heavy metal poisoning 1. BAL (British Anti Lewisite)/ Dimercaprol Indications: B - Bismuth poisoning A - Arsenic poisoning L - Lead poisoning Contra-Indications Cadmium poisoning Fe poisoning 2. Ca Na2 EDTA Indications M – Manganese poisoning I – Iron poisoning L – Lead poisoning K – Cadmium poisoning 3. d- Penicillamine Used for Cu poisoning and Wilson disease 4. Fe chelating agentsQ Desferioxamine Injectable DOC for acute Iron poisoning Deferipirone Oral Used for chronic Iron over load Previous Years Questions Q1. Which of the following is an adverse effect of orlistat? A. Suicidal tendancy B. Steatorrhea C. Weight gain D. Hyperglycemia Q2. Longest acting phosphodiesterase inhibitor among the following drugs is? A. Sildenafil B. Vardenafil C. Tadalafil D. Phentolamine Q3. Which of the following is FDA-approved drug for long term treatment of obesity? A. Sibutramine B. Liraglutide C. Metformin D. Fenfluramine Q4. An 11-year-old boy presented to emergency with vom iting. Parents gave history of consuming 10-15 tablets of ferrous sulphate a day before. What is the antidote of iron for treatment of this patient? A. Dimercaprol B. Desferrioxamine C. d- Penicillamine D. Activated charcoal Q5. A patient presented with hyperkalemia. Which of the following drugs can cause intracellular movement of and thus decrease in extracellular potassium levels? A. Atropine B. Lactic acid C. Epinephrine D. Glucagon Answers 1. - B 2. - C 3. - B 4. - B 5. - C
Ad

More Related Content

PDF
Pharmacology quick revision notes in.pdf
bymagrayfazu46
90 slides9.6K views
PDF
Pharmacology Short Notes and Mnemonics By Muhammad Ramzan Ul Rehmaan.pdf
byHadiaHadia3
358 slides13.2K views
PPTX
Pharmacology Rapid Revision slides notes
byNarendraGandhi4
202 slides3.6K views
PDF
Pharmacology Question Bank for II MBBS: Essential Concepts and Practice Quest...
byShivankan Kakkar
4 slides3.8K views
PDF
Drugs acting on blood and blood forming organs
byUrmila Aswar
52 slides27.7K views
PPTX
Distribution of drugs pharmacology ppt
byPranatiChavan
24 slides1.6K views
PPTX
Routes of drug administration
byAmit Kumar
38 slides1.9K views
PDF
MCQs in Pharmacology ( PDFDrive ).pdf
byEmaanFatima90
408 slides2.9K views
Pharmacology quick revision notes in.pdf
bymagrayfazu46
90 slides9.6K views
Pharmacology Short Notes and Mnemonics By Muhammad Ramzan Ul Rehmaan.pdf
byHadiaHadia3
358 slides13.2K views
Pharmacology Rapid Revision slides notes
byNarendraGandhi4
202 slides3.6K views
Pharmacology Question Bank for II MBBS: Essential Concepts and Practice Quest...
byShivankan Kakkar
4 slides3.8K views
Drugs acting on blood and blood forming organs
byUrmila Aswar
52 slides27.7K views
Distribution of drugs pharmacology ppt
byPranatiChavan
24 slides1.6K views
Routes of drug administration
byAmit Kumar
38 slides1.9K views
MCQs in Pharmacology ( PDFDrive ).pdf
byEmaanFatima90
408 slides2.9K views

What's hot

PPTX
Drug absorption
byCyberjaya University College of Medical Sciences
52 slides160.2K views
PDF
Arun kumar mnemonics pdf.pdf arun kumar mnemonics pdf 2
byAl-YAQIN DIAGNOSTIC ULTRASONIC CLINIC BAGHDAD
208 slides146.6K views
PDF
Important Pharmacology Topics for MBBS Students.pdf
byDiginerve
20 slides8.1K views
PPTX
Drug promotional literature
byAkhil Agarwal
41 slides10.9K views
PPTX
Criticise rewrite 1
byArchana Dhavalshankh
43 slides1.9K views
PDF
Kd tripathi MCQs in pharmacology
byMohamed Haggi Khalif
415 slides161.8K views
PPTX
Writing a prescription (pharmacology practical class)
byPravin Prasad
20 slides21.3K views
PPTX
P drugs for given case
bykopalsharma85
27 slides7K views
PPTX
Local anaesthetics
byMayur Chaudhari
44 slides44.8K views
PPTX
Ans pharmacology
bySimba Syed
21 slides42.1K views
PPTX
Pharmacology KDT problem based questions
byAbhinav Kumar
115 slides10.4K views
PPTX
Local anesthetics
bySubramani Parasuraman
20 slides19.9K views
PPTX
Necrosis and types
bySyeda Maryam
24 slides5K views
PPTX
Cell injury pathology revision notes
byTONY SCARIA
150 slides31.4K views
PPTX
Sedatives hypnotics
byHARIPRASAD MG
27 slides2.1K views
PPT
Antibiotics
byshabeel pn
30 slides14.6K views
PPTX
Local anesthetic agents
byCHRIS ALUMONA
54 slides8.3K views
PPTX
Skeletal Muscle Relaxants
byPradeep Singh Narwat
30 slides100.2K views
PPTX
Adrenergic receptors
byAmy Mehaboob
21 slides54.8K views
PPTX
PHARMACOLOGY PRACTICAL QUESTION PAPER SPOTTING
bychandreshmishra13
56 slides10.6K views
Drug absorption
byCyberjaya University College of Medical Sciences
52 slides160.2K views
Arun kumar mnemonics pdf.pdf arun kumar mnemonics pdf 2
byAl-YAQIN DIAGNOSTIC ULTRASONIC CLINIC BAGHDAD
208 slides146.6K views
Important Pharmacology Topics for MBBS Students.pdf
byDiginerve
20 slides8.1K views
Drug promotional literature
byAkhil Agarwal
41 slides10.9K views
Criticise rewrite 1
byArchana Dhavalshankh
43 slides1.9K views
Kd tripathi MCQs in pharmacology
byMohamed Haggi Khalif
415 slides161.8K views
Writing a prescription (pharmacology practical class)
byPravin Prasad
20 slides21.3K views
P drugs for given case
bykopalsharma85
27 slides7K views
Local anaesthetics
byMayur Chaudhari
44 slides44.8K views
Ans pharmacology
bySimba Syed
21 slides42.1K views
Pharmacology KDT problem based questions
byAbhinav Kumar
115 slides10.4K views
Local anesthetics
bySubramani Parasuraman
20 slides19.9K views
Necrosis and types
bySyeda Maryam
24 slides5K views
Cell injury pathology revision notes
byTONY SCARIA
150 slides31.4K views
Sedatives hypnotics
byHARIPRASAD MG
27 slides2.1K views
Antibiotics
byshabeel pn
30 slides14.6K views
Local anesthetic agents
byCHRIS ALUMONA
54 slides8.3K views
Skeletal Muscle Relaxants
byPradeep Singh Narwat
30 slides100.2K views
Adrenergic receptors
byAmy Mehaboob
21 slides54.8K views
PHARMACOLOGY PRACTICAL QUESTION PAPER SPOTTING
bychandreshmishra13
56 slides10.6K views
Ad

Similar to Pharmacology_RR.pdf by Dr Gobind Rai Garg

PPT
FARMACODINÁMICA FUNCIONES RESPUESTA DE DROGAS
byelvgonzalesc
80 slides21 views
PPTX
BASIC PHARMACOLOGY (recovered).pharmacol
bynkubagregory
859 slides211 views
PPTX
Pharmacology_Chapter1_Full_50_Slides.pptx
byaniqueshahid48
49 slides83 views
PPT
1. pharmacokinetics pharmacodynamics ppt
byanielyadav005
27 slides185 views
PPT
1. pharmacokineticspharmacology ppt for pcl students.ppt
byanielyadav005
27 slides26 views
PPTX
Pharmacology
byAdnan ul Islam
57 slides693 views
PPTX
OCCULAR PHARMACOLOGY.pptx
bygeniousg1
83 slides392 views
PDF
Memorizing notes.pdf
byPearlynJohnBritto1
17 slides102 views
PPTX
PHARMACOLGY I-Lecturer 1.pptx
byKeyaArere
39 slides122 views
PPTX
nursunf INTRODUCTION TO PHARMACOLOGY 1.pptx
byFREDRICK CIIRA
25 slides84 views
PPTX
Pharmacology a subject of interest
byNirmala College of Health Science
30 slides264 views
PPTX
pharmacology basics including pharmacodynamics.pptx
bySHIVAPRASADPAUDYAL
59 slides15 views
PPTX
General_Pharmacology_Quick_Revision_2ndYear_BDS.pptx
bymaddieinfo7
14 slides20 views
PPT
Pharmacology
bytejamba
39 slides1.4K views
PPTX
Introduction of pharmacology first years
byssuser4c546a
24 slides124 views
PDF
Pharmacology basics
byKhanIsmail2
41 slides97 views
PPT
Pharmacology_Basics.ppt
byssuser660bb1
41 slides46 views
PDF
Clinical Pharmacokinetics and Pharmacodynamics
byKarmenaivx
61 slides7 views
PDF
Clinical Pharmacokinetics and Pharmacodynamics
byKarmenaivx
61 slides35 views
PDF
Clinical Pharmacokinetics and Pharmacodynamics
byKarmenaivx
61 slides11 views
FARMACODINÁMICA FUNCIONES RESPUESTA DE DROGAS
byelvgonzalesc
80 slides21 views
BASIC PHARMACOLOGY (recovered).pharmacol
bynkubagregory
859 slides211 views
Pharmacology_Chapter1_Full_50_Slides.pptx
byaniqueshahid48
49 slides83 views
1. pharmacokinetics pharmacodynamics ppt
byanielyadav005
27 slides185 views
1. pharmacokineticspharmacology ppt for pcl students.ppt
byanielyadav005
27 slides26 views
Pharmacology
byAdnan ul Islam
57 slides693 views
OCCULAR PHARMACOLOGY.pptx
bygeniousg1
83 slides392 views
Memorizing notes.pdf
byPearlynJohnBritto1
17 slides102 views
PHARMACOLGY I-Lecturer 1.pptx
byKeyaArere
39 slides122 views
nursunf INTRODUCTION TO PHARMACOLOGY 1.pptx
byFREDRICK CIIRA
25 slides84 views
Pharmacology a subject of interest
byNirmala College of Health Science
30 slides264 views
pharmacology basics including pharmacodynamics.pptx
bySHIVAPRASADPAUDYAL
59 slides15 views
General_Pharmacology_Quick_Revision_2ndYear_BDS.pptx
bymaddieinfo7
14 slides20 views
Pharmacology
bytejamba
39 slides1.4K views
Introduction of pharmacology first years
byssuser4c546a
24 slides124 views
Pharmacology basics
byKhanIsmail2
41 slides97 views
Pharmacology_Basics.ppt
byssuser660bb1
41 slides46 views
Clinical Pharmacokinetics and Pharmacodynamics
byKarmenaivx
61 slides7 views
Clinical Pharmacokinetics and Pharmacodynamics
byKarmenaivx
61 slides35 views
Clinical Pharmacokinetics and Pharmacodynamics
byKarmenaivx
61 slides11 views
Ad

Recently uploaded

PPTX
Comprehensive Guide to Concepts and Principles of e-Sports for Educators
byKarlaCenteno9
60 slides37 views
PDF
Comprehensive Biology 1 Lesson Exemplars for Senior High School
byDepEd
250 slides25 views
PPTX
Comprehensive Guide to Computing Gross and Net Pay in the Philippines
byMarinelJoyceEstebanB
34 slides56 views
PPTX
Applying Life Skills for Personal Growth and Social Success in Grade 11
byBenjieBaga1
23 slides82 views
PPTX
DepEd Order No. 006, S. 2026: Ensuring Safe and Motivating Learning Environme...
byjohnphilipapulog2
13 slides252 views
PPTX
Unmasking Perspectives in Communication: Attitudes, Assumptions, and Cultural...
byabeguelpore
12 slides40 views
PPTX
Understanding Translational and Rotational Motion in Machines for Efficient D...
byemylazatin1
30 slides112 views
PPTX
Grade_11_General_Science_The_Physics_of_Fluids.pptx
byLourdesDamasco
15 slides173 views
PPTX
G5_SCIENCE GRADE 5 TERM 1 _PPT_T1_W3.pptx
bylodie_93
84 slides58 views
PDF
Unit 2. A. Plant Drug Cultivation and Collection| Pharmacognosy Unit 2 | B.Ph...
byAshaGolasangimath
44 slides169 views
PPTX
Philosophical Analysis, Abstraction, and Reflection: Pathways to Wisdom and M...
byaureliorholdan45
17 slides302 views
PPTX
Understanding the Differences Between General and Professional Communication ...
byCBalamuruganC
22 slides102 views
PDF
Powdery Mildews by Sarah Ashfaq 51 Botanist PU.PDF
byUGI
46 slides26 views
PPTX
Using Units in Simple Science Activities.pptx
byMelissaLago1
9 slides28 views
PPTX
LAMINAR FLOW HOODS. Nursing.pptx........
byGaneshChakor2
11 slides49 views
PPTX
Comprehensive Exploration of Digital Audio Workstations, Sampling, Photograph...
byKarlaCenteno9
33 slides80 views
PPTX
Analyzing Coherence, Unity, and Voice in Anglo-American Poetry for Grade 9
byLenojdev
66 slides60 views
PDF
Murshidabad university B.Sc. Sericulture SER-M-201 Notes by Ankit Mondal
byankitmondal993357
56 slides91 views
DOCX
Culturally Significant Communication and Critical Media Literacy for Grade 11
byNeliaAbueva1
4 slides71 views
PPTX
Exploring Sustainable Education Futures with AI: Tools and Strategies
byKai Pata
16 slides107 views
Comprehensive Guide to Concepts and Principles of e-Sports for Educators
byKarlaCenteno9
60 slides37 views
Comprehensive Biology 1 Lesson Exemplars for Senior High School
byDepEd
250 slides25 views
Comprehensive Guide to Computing Gross and Net Pay in the Philippines
byMarinelJoyceEstebanB
34 slides56 views
Applying Life Skills for Personal Growth and Social Success in Grade 11
byBenjieBaga1
23 slides82 views
DepEd Order No. 006, S. 2026: Ensuring Safe and Motivating Learning Environme...
byjohnphilipapulog2
13 slides252 views
Unmasking Perspectives in Communication: Attitudes, Assumptions, and Cultural...
byabeguelpore
12 slides40 views
Understanding Translational and Rotational Motion in Machines for Efficient D...
byemylazatin1
30 slides112 views
Grade_11_General_Science_The_Physics_of_Fluids.pptx
byLourdesDamasco
15 slides173 views
G5_SCIENCE GRADE 5 TERM 1 _PPT_T1_W3.pptx
bylodie_93
84 slides58 views
Unit 2. A. Plant Drug Cultivation and Collection| Pharmacognosy Unit 2 | B.Ph...
byAshaGolasangimath
44 slides169 views
Philosophical Analysis, Abstraction, and Reflection: Pathways to Wisdom and M...
byaureliorholdan45
17 slides302 views
Understanding the Differences Between General and Professional Communication ...
byCBalamuruganC
22 slides102 views
Powdery Mildews by Sarah Ashfaq 51 Botanist PU.PDF
byUGI
46 slides26 views
Using Units in Simple Science Activities.pptx
byMelissaLago1
9 slides28 views
LAMINAR FLOW HOODS. Nursing.pptx........
byGaneshChakor2
11 slides49 views
Comprehensive Exploration of Digital Audio Workstations, Sampling, Photograph...
byKarlaCenteno9
33 slides80 views
Analyzing Coherence, Unity, and Voice in Anglo-American Poetry for Grade 9
byLenojdev
66 slides60 views
Murshidabad university B.Sc. Sericulture SER-M-201 Notes by Ankit Mondal
byankitmondal993357
56 slides91 views
Culturally Significant Communication and Critical Media Literacy for Grade 11
byNeliaAbueva1
4 slides71 views
Exploring Sustainable Education Futures with AI: Tools and Strategies
byKai Pata
16 slides107 views

Pharmacology_RR.pdf by Dr Gobind Rai Garg

  • 1.
  • 2.
    Pharmacology is thescience dealing with drugs. Two branches: 1. PharmacoKinetics → Effect of Body on Drug 2.PharmacoDynamics → Effect of Drug on Body PHARMACOKINETICS • • Aka ADME Study – – Absorption – – Distribution – – Metabolism – – Excretion 1. Absorption • • It is the movement of drug from site of administration to blood. • • Lipid Solubility is the most important factor in absorption.Q When The Medium Is Same, Then The Drug Will Cross DRUG MEDIUM FORM SOLUBILITY CROSS Acidic Basic Acidic Basic Acidic Basic Basic Acidic Non ionized Non ionized lonized lonized Lipid Soluble Lipid soluble Water Soluble Water Soluble   x x Bioavailability • • It is the fraction of given dose that reaches the systemic circulation in unchanged form Factors affecting: 1. Absorption → Absorption → ↑ Bioavailability Chapter - 1 General Pharmacology ↓ Absorption → ↓ Bioavailability 2. First Pass metabolism/Pre systemic metabolism ↑ First Pass metabolism → ↓ Bioavailability ↓ First Pass metabolism → ↓ Bioavailability Note: If we give a drug by IV route, bioavailability is 100%Q Plasma Concentration Vs Time Graph Cmax Maximum concentration obtained by a particular dose Should lie between MTC and MEC Tmax Time in which plasma concentration becomes maximum Tells Rate of absorption AUC Total area covered by graphQ Tells Extent of absorption 2. Distribution • • Distribution is a measure of amount of drug in tissues after absorption in the systemic circulation • • It depends upon lipid solubility and plasma protein binding. Plasma Protein BindingQ • • Acidic drugs bind to → Albumin • • Basic drugs bind to → a1 Acid Glycoprotein High PPB drugs have • • Low Vd • • Long duration of action • • More drug interactions • • Dialysis not useful in poisoning • • Less Filtration
  • 3.
    3 Pharmacology Volume of Distribution(Vd)Q Amount given Plasma concentration Vd = • • Volume of Distribution (Vd) ∝ Amount of Drug in Tissues More Vd → More distribution Loading Dose [LD] Initial high dose given to start the action LD = Vd x Target Plasma Concentration Maintenance DoseQ Repeateddosesgiventomaintaintheplasmaconcentration. MD = CL x Target PC 3. Metabolism Aim of Metabolism → To Make a Drug Water Soluble (Polar) PHASE I REACTIONSQ PHASE II REACTIONSQ Mostly catabolic Reactions Includes • • Oxidation (MC) • • Reduction • • Hydrolysis • • Cyclization • • Deamination Mostly anabolic reactions Includes • • Glucuronidation (MC) • • Glutathione conjugation • • Acetylation • • Methylation • • Sulfate conjugation Purpose of Phase I → Expose the Functional Group on the drug Purpose of Phase II → Makes the drug water soluble Enzymes • • Divided into Microsomal and Non-microsomal Microsomal Non-microsomal Present in smooth endoplasmic reticulum Present outside SER Can be induced or inhibited Cannot be induced or inhibited Enzyme InducersQ Enzyme inhibitorsQ G -Griseofulvin P -Phenytoin R -Rifampicin S -Smoking Cell -Carbamazepine Phone -Phenobarbitone Vit -Valproate K -Ketoconazole Can’t -Cimetidine Cause -Ciprofloxacin Enzyme -Erythromycin Inhibition -Isoniazid Cytochrome p450 Enzymes These are one type of microsomal enzymes. CYP3A4 CYP2D6 CYP2C19Q C : Cyclosporine T : Tacrolimus S : Statins C : CAT (Cisapride, Astemizole, Terfenadine) A :Amiodarone N :Navirs 2 : b-Blockers D:Anti-Depressants 6:Anti-Anthythmies (except amiodarone) Clopidogrel CYP2C9Q Warfarin Phenytoin Clopidogrel CYP2C19 PPI – Active Therefore, PPIs are avoided with clopidogrel 4. Excretion
  • 4.
    4 Cerebellum Quick RevisionNotes Glomerular Filtration • • Lipid soluble as well as water soluble drugs can be filtered • • Filtration is inversely proportional to Plasma Protein binding Tubular Reabsorption • • 99% of GFR is reabsorbed – – Lipid soluble drugs reabsorbed – – Water soluble drugs excreted Tubular Secretion • • Due to pumps/transporters in proximal tubules • • These transporters are Saturable (One drug can be transported at one time) • • Probenecid prolongs action of penicillins by inhibiting tubular secretion Kinetics of Elimination Half Life [t1/2 ] • • It is the time in which plasma concentration of a drug becomes half. • • Half-life is constant in first order kinetics. Question: t1/2= 6hrs, after 1 day • • How much drug remains in body → 6.25% • • How much drug eliminated from body →100-remaining→ 93.75% Importance of t ½: • • Dose cannot be calculated • • Dosing Interval/ Frequency can be known Formula of Half-life: t K 1 2 0 693 = . (where, K is elimination rate constant) As So, K CL Vd = t X Vd CL 1 2 0 693 = . Order of Kinetics First order kinetics Zero order kineticsQ → Fraction is constant → Amount is constant R a PC CL = Constant t½ = Constant R = Constant CL a 1/ PC t½ a PC • • Majority of drugs follow First Order Kinetics Drugs Following Zero Order Kinetics areQ Zero → Zero order Kinetics W → Warfarin A → Alcohol/Aspirin T → Theophylline T → Tolbutamide Power → Phenytoin PHARMACODYNAMICS: It deals with action of a drug as well as the mechanism of action Major mechanism of action of a drug are through enzymes or through receptors. Enzyme inhibitionQ Km Vmax Competitive ↑ - Non competitive - ↓ Lineweaver Burke Plot: • • Also known as double reciprocal plot • • Graph between 1/S (on X-axis) and 1/V (on Y-axis)
  • 5.
    5 Pharmacology • • X-axis tellsKm and Y-axis tells Vmax • • If lines intersect at X-axis, it is non-competitive inhibition • • If lines intersect at Y-axis, it is competitive inhibition Classification of DrugsQ Drug Intrinsic Activity Agonist Maximum [+1] Partial Agonist Submaximum [0 to 1] Inverse Agonist Opposite action [-ve] Antagonist No action of itself but interfere with action of other drugs [0] Classification of Receptors 1. lonotropic Receptors • • The receptors present on ion channels are known as ionotropic receptors. • • Fastest acting receptors 2. Enzymatic Receptors • • These are present on cell membrane with intracellular and extracellular ends. • • Drug binds outside and enzyme is activated inside and action is produced • • Aka Tyrosine Kinase Receptors 3. G-Protein Coupled Receptors [GPCR] Works by one out of the 3 mechanisms • • By changing the level of cAMP • • Can act through Ca2+ • • Can open the ion channels
  • 6.
    6 Cerebellum Quick RevisionNotes Types of G proteins Type Mechanism Second/Third messenger GS Stimulate adenylate cyclase ↑ cAMP Gi Inhibit adenylate cyclase ↓ cAMP Gq Convert PIP2 to IP3 and DAG IP3 DAG Calcium 4. Intracellular Receptors A. Cytoplasmic Receptors B. Nuclear Receptors • • Only Lipid soluble drugs acts through these receptors • • Thus, whether a drug binds the cytoplasmic receptors or the nuclear receptors, it will finally work through DNA (nuclear mechanism) • • These are also called nuclear recetor superfamilty • • These are slowest acting receptors. Receptors Examples 1. Ionotropic GABAA , NMDA, NN , NM , 5HT3 2. Enzymatic Cytokines, Prolactin, Insulin, GH 3. Intracellular A. Cytoplasmic B. Nuclear Vit D, Glucocorticoids, Mineralocorticoids Vit A, Thyroid hormones, Sex hormones 4. GPCR Most others Log Dose Response Curve (Log DRC) • • S-shaped curve [Sigmoid Curve) • • Clinically more useful than DRC • • 3 important parameters obtained from log DRC: 1. Potency 2. Efficacy 3. Slope Potency • • To produce a similar response if a drug is required in lesser dose, it is more potent • • On log DRC, left-sided curve is more potent drug whereas right-sided curve is less potent Efficacy • • Relates to maximum effect of a drug regardless of dose • • Higher the curve, more is efficacy H - Height tells aboutQ E - Efficacy L - Left side drugs are more P - Potent C → Most efficacious (Highest curve) D → Least efficacious (Lowest curve) D → Most potent (Most left) B → Least potent (Most right)
  • 7.
    7 Pharmacology Quantal DRC • • ForAll or None phenomenon, where grade of response cannot be plotted. • • Percentage of subjects responding are kept on Y-axis • • Tells about effect of a drug in population i) If 50% respond to a particular dose → Then it is called ED50 (Median Effective dose) ii) If 50% of animals die after receiving a particular dose it is median lethal dose (LD50 ). Therapeutic index = LD50 /ED50 Q • • Therapeutic index is margin of the safety of a drug The Drugs and Cosmetics Act – – An act to regulate the import, manufacture, distribution and sales of drugs. • • Spurious drug: Imitation of or substitute of another drug in a manner likely to deceive the name of another drug. The less known pharmaceutical company try to take advantage of reputation of a well-known company. • • Misbranded drug: If a drug is not labelled in prescribed manner or its label contains any statement which makes any false claims for the drug. • • Adulterated drug: If it contains filthy, patrid or decomposed substances. Clinical Trials Testing of drugs in humans is called clinical trials • • Licensing Authority to give approval for a new drug in USA is FDA whereas in India it is DCGI (Drug Controller General of India) Q Q Q Phase Zero Clinical Trials • • Micro-dosing study • • It is conducted on humans • • Maximum amount of drug given is 100 mcg or (1/100)th of Human Equivalent Dose, whichever is lower • • Radiolabeled substances are added with this sub therapeutic dose to know the Pharmacokinetics of the drug. • • It is not mandatory Q
  • 8.
    8 Cerebellum Quick RevisionNotes Pregnancy Categories: Drugs are categorized into 5 groups according to safety in pregnancy Category Special points A Safest in pregnancy B C D X Contra-indicated in pregnancy e.g. ThalidomideQ Note: • • Schedule X drugs and category X drugs are totally different. • • Schedule X include narcotic and psychotropic drugs e.g. ketamine. • • Category X contain teratogenic drugs like thalidomide • • Schedule H drugs require prescription of a RMP. SAFE AND UNSAFE DRUGS IN PREGNANCY Condition Drugs safe in Pregnancy Drugs to beQ avoided in Pregnancy Hypertension Labetalol, Methyldopa ACE Inhibitors and ARBs Anti-coagulants Heparin Warfarin Bipolar disorders Anti-psychotics Valproate (Contra- indicated) Lithium (Avoid) Anti-thyroid Propylthiouracil Carbimazole (1st trimester) Anti-microbials Penicillins, Cephalosporins Macrolides Tetracyclines Quinolones Aminoglycosides Anti-Epileptics Levetiracetam Lamotrigine Valproate Enteric Coating of Drugs: • • This is a coating that dissolves in alkaline medium only. • • It can be used for – – Protecting the acid labile drugs from gastric acid, e.g., proton pump inhibitors. – – It can protect gastric mucosa from irritant drugs e.g. NSAIDS – – It increases the absorption of drugs that are preferentially absorbed distal to stomach. Fixed Dose Combinations (FDC): When two or more drugs are combined to- gether in a particular ratio. Advantages: • • Compliance improves • • One drug may reduce the adverse effects of the other drug • • Efficacy may increase • • Cost may decrease Disadvantages: • • May be used irrationally. • • If adverse effect occurs, it cannot be ascribed to one drug. • • Drugs with different pharmacokinetics cannot be combined. • • Dose of one drug cannot be altered independently as per requirement. Prescription Writing Prescription is the written order by the doctor to the pharmacist to dispense some medication.Q Note: • • Without date and signature (initials), the prescription is invalid. • • Drug name should never be written in short form (e.g., write paracetamol, not PCM) • • Abbreviations like OD, BD, HS should not be usedQ • • In dose of drug – – Leading zeros should always be mentioned (e.g., 0.5 mg is correct but .5 mg is wrong) – – Trial zeros should never be mentioned (e.g., 5 mg is correct but 5.0 mg is wrong) – – Microgram should be written as mcg not μg.Q
  • 9.
    9 Pharmacology Q8. Which ofthe following drugs follow zero order kinetics? A. Phenytoin B. Diclofenac C. Morphine D. Propranolol Q9. Identify the type of inhibition from the given graph A. Competitive B. Non-competitive C. Un-competitive D. Allosteric Q10. True about non-competitive inhibition is A. Km remains same, Vmax decreases B. Km increases, Vmax remains same C. Km decreases, Vmax increases D. Km increases, Vmax increases Q11. Identify the missing substance X marked in the box in the given diagram A. G protein B. Protein C C. Cyclic AMP D. Calcium Previous Years Questions Q1. Which of the following factor in PC vs time graph is a measure of extent of drug absorption of a drug? A. Area under the curve B. Half life C. Cmax D. Tmax Q2. Rate of administration of a drug is equal to rate of elimination. How will you calculate the dosing rate of the drug to maintain steady state concentration? A. Dosing rate = Vd x target plasma concentration B. Dosing rate = CL x target plasma concentration C. Dosing rate = Vd/target plasma concentration D. Dosing rate = CL/target plasma concentration Q3. Anionic and slightly acidic drugs usually bind to A. Albumin B. Alpha acid glycoprotein C. Ceruloplasmin D. Globulin Q4. High plasma protein binding of a drug results in: A. Decreased glomerular filtration B. High volume of distribution C. Lowers duration of action D. Less drug interaction Q5. A patient with stroke was started on clopidogrel. He developed another episode of stroke 6 months later. Which of the following is the likely cause? A. Rapid metabolism by CYP 1A2 B. Poor metabolism by CYP 2C19 C. Poor metabolism by CYP 2D6 D. Poor metabolism by CYP 2E1 Q6. Which of the following treatment option is utilized in salicylate poisoning? A. Alkalinization of urine B. Acidificaition of urine C. Alkalinization of blood D. Acidification of blood Q7. Elimination rate constant of a drug is 0.05/hr. What is its half life? A. 6.5 hr B. 20 hr C. 13.9 hr D. 8 hr Answers 1. - A 2. - B 3. - A 4. - A 5. - B 6. - A 7. - C 8. - A 9. - A 10. - A 11. - C
  • 10.
    10 Cerebellum Quick RevisionNotes Q12. Which of the following statement is correct regarding the given graph? A. Drug A is agonist and Drug B represents inverse agonist B. Drug C represents agonist and Drug D is inverse agonist C. Drug A is agonist and Drug D is inverse agonist D. Drug B is partial agonist and Drug C is inverse agonist Q13.TypeofstimulatoryGproteininPIP2-Phospholipase activation pathway is A. Gs B. Gi C. Gq D. Go Q14. Drug acting via tyrosine kinase receptor is A. TRH B. TSH C. Insulin D. MSH Q15. Which of the following drugs act through intracellular receptors? A. Thyroxin B. Glucagon C. Epinephrine D. Parathyroid hormone Q16. Find therapeutic index of a drug from the information given below in the graph A. 1 B. 2 C. 4 D. 8 Q17. What does LD50 signifies A. It is the dose at which 50% of animals will die B. It is the dose at which 50 animals will die C. It is the dose at which 50% patients will get the desired response D. It is drug that will be effective at 50% dose Q18. Which of the following statements about these drugs is true? A. Drug A is most potent B. Drug A and B have equal efficacy but B is more potent than drug A C. Drug C is least potent D. Drug B has more potency but less efficacy than drug A Q19. Which of the following statement is correct about clinical trials? A. New drug application is filed with Phase 2 clinical trials B. Phase 0 clinical trials is for checking the pharma- cokinetics of the drug C. In Phase 3, open label studies are done D. Phase 2 is post marketing surveillance. Answers 12. - C 13. - C 14. - C 15. - A 16. - C 17. - A 18. - A 19. - B
  • 11.
    11 Pharmacology Q20. New drugapplication is filed after which phase of clinical trials? A. Phase 1 B. Phase 2 C. Phase 3 D. Phase 4 Q21. Manufacturer of a drug company labels the drug contains 500 mg paracetamol. On quantitative analysis by the authorities, it was found to contain only 200 mg of drug. According to drugs and cosmetics act 1940, this type of drug is known as? A. Spurious drug B. Adulterant drug C. Unethical drug D. Misbranded drug Q22. Identify the true statement regarding Clinical Trials: A. Phase 1 is done to determine efficacy in patients B. Healthy volunteers are recruited for the first time in Phase II C. Randomized Controlled Trials in patients is done in Phase III D. Phase IV is Pharmacokinetics study in animals Q23. All of the following are advantages of enteric coated tablets except A. It increases the half-life of the drug B. It protects acid labile drugs from gastric pH C. It increases the absorption of drugs that are preferentially absorbed distal to stomach. D. It protects stomach from irritant drugs Q24. Category A, B, C, D, X division of drugs is based on A. Safety in pregnancy B. Dose adjustment in renal failure C. Therapeutic index and safety D. Over the counter use of drug Q25. Variation in drug responsiveness to a particular dose of the drug in different individuals can be obtained from: A. Graded Dose Response Curve B. Efficacy C. Potency D. Quantal Dose Response Curve Q26. Which of the following statement is true regarding Fixed Dose Combination of drugs? A. Adverse effect of one drug may be reduced by the other drug B. Two drugs with different pharmacokinetics can be combined easily C. Dose of one drug can be altered independently as per requirement D. Adverse effect can be ascribed to a single drug Q27. Which of the following drug must be sold by retail only production of a prescription by a registered medical practitioner? A. Schedule H B. Schedule G C. Schedule X D. Schedule M Q28. As an Indian medical intern, which of the following is the correct format for prescription of alprazolam? A. Tablet alprazolam 0.5 mg once a day before bed time for 7 days B. Tablet alprazolam 0.5 mg HS for 7 days C. Tablet alprazolam 500 mcg one tablet OD for 7 days D. Tablet alprazolam ½ mg tablet HS daily Answers 20. - C 21. - D 22. - C 23. - A 24. - A 25. - D 26. - A 27. - A 28. - A
  • 12.
    Location Neurotrans- mitter Preganglionic parasympathetic Preganglionicsympathetic Postganglionic parasympathetic Postganglionic sympathetic • • At all places • • At sweat glands ACh ACh ACh NA ACh Actions: Location Parasympathetic Sympathetic Heart Bronchus GIT Bladder Glands Pupil Sexual system ↓↓ Bronchoconstriction Diarrhea Contract ↑ Secretions Miosis Erection + + + Bronchodilation Constipation Relax ↓ Secretions Mydriasis Ejaculation PARASYMPATHETIC SYSTEM Major neurotransmitter is ACh It works on cholinergic receptors Cholinergic Receptors Nicotinic Receptor Muscarinic Receptor NN → Ganglia NM → NMJ (require optimal stimulation) M1 → Stomach: ↑HCl M2 → Heart: ↓ HR, ↓ Conduction M3 → Bronchus : BC GIT : ↑ Peristalsis Bladder : ↑ Contraction Glands : ↑ Secretions Pupil : Miosis Chapter - 2 Autonomic Nervous System Origin: Neurotransmitters:
  • 13.
    13 Pharmacology CHOLINERGIC DRUGS: Drugs stimulatingthe parasympathetic system can be: Directly Acting Cholinergic Drugs: DRUG ACTS ON ACTION INDICATION Pilocarpine Pupil [M3] Miosis Angle closure glaucoma Q Indirectly Acting Cholinergic Drugs: • • These drugs act by inhibiting AChE. • • These may be reversible or irreversible AChE inhibitors. • • Reversible AChE inhibitors are used clinically whereas irreversible AChE inhibitors are toxic. Reversible AChE Inhibitors: Uses of NeostigmineQ Irreversible AChE Inhibitors Include Organophosphates - Malathion Parathion Carbamates - Carbaryl Propoxur Organophosphate Poisoning: Clinical features: Receptor stimulated Feature M1 Aciditiy M2 Bradycardia and Hypotension M3 • • Pin point pupil • • ↑ Secretions • • Diarrhea • • Urination • • Bronchoconstriction M1, M2, M3 Coma NM Muscle weakness NN Tachycardia and Hypertension Note: • • Nicotinic symptoms (NN ) are extremely rare. • • If pin point pupil with increase in secretions are present, diagnosis of OP poisoning is almost sure. Treatment 1. AtropineQ • • DOC For OP and Carbamate poisoning • • Given by iv route (every 5 min) till signs of atropinization occur. • • Atropine cannot reverse muscle weakness Signs of Atropinization • • ↓ Secretions → Most reliable (Most specific) sign • • Mydriasis → Most commonly used sign • • Tachycardia → HR > 100 bpm Note: Atropine is not used in organochlorine (endrin) poisoning. 2. AChE Reactivators (Oximes)Q Pralidoxime [PAM] Di Acetyl Monoxime [DAM] • • Not DOC • • Only effective in OP Poisoning • • PAM acts only peripherally, DAM has both central as well as peripheral actions.
  • 14.
    14 Cerebellum Quick RevisionNotes ANTICHOLINERGIC DRUGS Organ Receptor blocked Drugs Uses Stomach M1 Pirenzepine Telenzepine Peptic ulcer Heart M2 Atropine (DOC) Bradycardia AV block Bronchus M3 Ipratropium Tiotropium Bronchial asthma COPD Bladder M3 S- Solefenacin O- Oxybutynin F- Flavoxate T - Tolterodine BladDAR- DARifenacin Overactive bladderQ EYE M3 Atropine Homatropine Cyclopentolate Tropicamide Longest acting: Atropine Shortest acting: Tropicamide Fundoscopy Refraction testing Iridocyclitis DOC in children–Atropine eye ointment ATROPINE POISONING: (ANTICHOLINERGIC POISONING) • • Patient has a history of taking some wild fruit (Dhatura/Belladona) and presents withQ D – Dry mouth, Delirium H – Hyperthermia A – Agitation T – Tachycardia U – Urinary R – Retention A – Accommodation lost (Blurred vision, Photophobia) • • DOC for treatment of atropine poisoning is physostigmine.Q SYMPATHETIC NERVOUS SYSTEM • • Major neurotransmitter is nor-adrenaline Adrenergic Receptors a1 a2 Location Action Presynaptic receptor → Acts like brake to sympathetic system Blood vessels Vasoconstriction Eye Mydriasis Prostatic urethra ↓ Outflow
  • 15.
    15 Pharmacology b1 b2 b3 Location Action LocationAction Location Action Heart ↑ HR, BP Lungs Bronchodilation Fat Lipolysis JG cells Renin secretion GIT Constipation Bladder Relax Bladder ↓ Out flow Glands ↓ Secretions Uterus Tocolytic Blood vessels Vasodilation Skeletal muscle spindle Tremors Liver ↑ Blood sugar Effect on blood vessels A1 -> C α1 – Cause vasoconstrictionQ B2 -> D β2 – Cause vasodilation Effect on metabolism: • • Sympathetic system protects from hypoglycemia by two mechanisms: Warning symptoms Hypoglycemia reversal • • Tachycardia (b1 ) • • Palpitations (b1 ) • • Tremor (b2 ) • • Sweating (M3 ) • • By changing metabolism (b2 ) - ⊕ Gluconeogenesis - ⊕ Glycogenolysis - ⊝ Glycogenesis • • Beta Blockers cause (in diabetic patients) 1. Masking of warning symptoms 2.Prevent reversal of hypoglycemia • • So, b blockers are contraindicated in diabetic patients. • • Sweating is only reliable symptom of hypoglycemia in diabetics on b blocker medication.Q ADRENERGIC DRUGS: These can be divided into: • • Indirectly Acting Drugs • • Directly Acting Drugs Indirectly Acting Drugs COCAINE - It acts by inhibiting reuptake of NAQ • • It is a local anaesthetic – – All LA cause vasodilation except cocaine – – Cocaine cause vasoconstriction and hypertension • • It is an addictive drug – – Shows tactile hallucinations (cocaine bugs): Scratching of skin – – Cause palatine perforation – – Overdose characterized by ƒ ƒ Agitation ƒ ƒ Ulcers or scratch marks on skin ƒ ƒ Sympathetic symptoms (Tachycardia, Mydriasis, Hypertension, MI) Note: Cocaine does not cause bradycardia since it is a sympathetic drug. Directly Acting Drugs 1.CATECHOLAMINES – Not effective orally Endogenous Exogenous Adrenaline (a1, a2, b1, b2) NA (a1, a2, b1) Dopamine (D1, b1, a1) Dobutamine (b1) Isoprenaline (b1, b2) Fenoldopam (D1) Uses of Catecholamines Adrenaline 1. Anaphylactic Shock • • DOC is Adrenaline • • Route of choice is I.M. or S.C. • • Concentration is 1:1000 (0.5 ml)Q 2. Cardiac Arrest • • CPR is done first • • Adrenaline is useful • • Concentration is 1:10,000Q • • Preferred routes are IV > Intraoseous > ET
  • 16.
    16 Cerebellum Quick RevisionNotes Nor-Adrenaline • • DOC for septic shock • • Effect is monitored by checking mean blood pressure Dopamine Acts onQ Receptors Dose (mcg/ kg/min) Organ Action D1 < 2 Blood vessels Vasodilation (Max in Renal BV) b1 2-10 Heart Stimulation a1 > 10 Blood vessels Vasoconstriction Uses 1. CHF 2. Shock + Oliguria [DOC] Dobutamine • • Mainly b1 agonist • • Used for CHF Fenoldopam • • Only D1 agonist • • Used for hypertensive emergencies Isoprenaline • • ↑ SBP but ↓ DBPQ • • Maximum increase in pulse pressure 2. NON-CATECHOLAMINES Stimulates Drugs Action a1 Phenylephrine eye drops Mydriasis without cycloplegia Methoxamine Mephentermine → Vasoconstriction → Used in shock Xylometazoline Oxymetazoline Naphozoline → Nasal decongestants a2 Clonidine Methyldopa →Brakeforsympatheticsystem →Usedforhypertension b2 Salbutamol Terbutaline Salmeterol Formoterol → Bronchodilation → Used for asthma by inhalational route Ritodrine Isoxsuprine → Tocolytic → Used for preterm labour b3 Mirabegron Overactive bladder Note: Beta-2 agonists can cause following adverse effects: – – T - Tremors – – T - Trachycardia – – T - T-wave changes in ECG (due to hypokalemia) – – Pulmonary edema - by ritodrine – – However, b2 agonists do not cause hypoglycemia.Q ANTI - ADRENERGIC DRUGS These may be alpha blockers or b - Blockers. ALPHA BLOCKERS These can be non-selective (α1 + α2 ) blockers or selective α1 blockers Non-selective α blocker α1 Blocker 1. Used in severe hypertension 2. Can cause severe tachycardia 1. Used in mild to moderate hypertension 2. Cannot cause severe tachycardia Non-Selective α Blockers Irreversible Reversible Phenoxybenzamine Phentolamine, Tolazoline Used for – Pheochromocytoma Used for – Cheese Reaction – Clonidine withdrawal Selective α1 Blockers • • Prazosin • • Terazosin • • Doxazosin • • Alfuzosin Uses • • BPH (Due to a1A blockade) • • Scorpion sting (D.O.C is Prazosin) Adverse Effect First Dose (Postural) Hypotension → a1 blockers always started at bed-time.Q Types of α1 receptors α1A α1B/1D On Prostatic Urethra On Blood Vessels TAMSULOSIN SILODOSIN • • No postural hypotension • • DOC for normotensives with BPH
  • 17.
    17 Pharmacology Benign Prostatic Hyperplasia:(BPH) α1A blockers • • Tamsulosin - Stops the dynamic component and do not affect the size of prostate i.e they are only for the symptoms of BPH but do not stop the growth of prostate. 5-α reductase inhibitors: • • Finasteride - Stops the conversion of Testosterone to DHT which control/stops the growth of Prostate in BPH (Static Component). 2. BETA (β) BLOCKERS Beta-1 + Beta-2 # (First Generation) Beta-1 # (Second Generation) Cardiac and non-cardiac uses Contraindicated in Asthma, DM and PVD Only cardiac uses Relatively safe 1. Beta-1# or Cardio-Selective or 2nd Generation Beta # New → Nebivolol Beta → Betaxolol Blockers → Bisoprolol Act → Acebutolol Exclusively → Esmolol At → Atenolol Myo → Metoprolol Cardium → Celiprolol → These are relatively safe in Asthma, PVD & DM 2. Intrinsic Sympathomimetic Activity [ISA] or Partial Agonists → Less chances of causing severe bradycardiaQ Contain → Celiprolol Partial → Pindolol Agonist → Alprenolol Activity → Acebutolol Indications Cardiac Uses 1. Hypertension 2. Classical Angina [C/I in Variant angina] 3. MI 4. Chronic CHF [C/I in acute CHF] 5. Arrhythmia Non-Cardiac Uses Play - Performance anxiety (DOC : Propranolol) The – Thyrotoxicosis (DOC : Propranolol) G – Glaucoma (Timolol is used) A – Akathisia (DOC : Propranolol) M – Migraine prophylaxis (DOC : Propranolol) E – Essential tremors (DOC : Propranolol) Adverse Effects and Contra-indications Due to β1 Blockade 1. ↓ Rate →Bradycardia(C/IinSicksinussyndrome) 2. ↓ Conduction → AV Block 3. ↓ Contractility → Acute CHF Due to β2 Blockade 1. Asthma 2. Peripheral vascular Disease 3. Diabetes mellitus 4. Variant angina. GLAUCOMA → Glaucoma is characterized by ↑ IOP: It may be due to – – ↑ Aqueous humor production – – ↓ Aqueous humor drainage
  • 18.
    18 Cerebellum Quick RevisionNotes DRUG OF CHOICE - POAG – Latanoprost - Angle closure glaucoma – Acetazolamide - Acute congestive glaucoma – Mannitol Adverse Effects MiotiCS – – Cataract – – Stenosis of NLD PGF2a Analogues (Latanoprost)Q – – Pigmentation of Iris (Heterochromia Iridis) – – Growth of eyelashes (Hypertrichosis) – – Fluid in macula (Macular edema) – – Contra-indicated in uveitis ApracLonIDine Q – – Lid retraction Brimonidine Q – – Causes Brain suppression in Infants (Leads to Apnea) – – C/l in children < 2yrs Netarsudil (Rho-kinase inhibitor)Q – – Cornea verticillata. ANS PRACTICALS 1. Ileum graphQ
  • 19.
    19 Pharmacology 2. Dog BloodPressure ExperimentQ A: Adrenaline B: Nor-adrenaline C: Isoprenaline Biphasic Response → Effect of high dose of adrenaline → Dog is given Phentolamine → α-blocker → BP → → Then, Epinephrine (high dose) is given → BP ↓ →No Biphasic Response produced → Called Vasomotor Reversal of Dale → Dog is given Atropine first → HR ↑ → After this, a high dose of ACh given → BP & HR ↑ → Nicotinic action appear → Stimulate sympathetic ganglia → Ephedrine given → BP ↑ → Same dose is repeated → Less ↑ in BP → Called Tachyphylaxis
  • 20.
    20 Cerebellum Quick RevisionNotes Previous Years Questions Q1. Which of the following action is expected on stimulation of muscarinic receptors? A. Erection B. Ejaculation C. Increased contraction of cardiac muscles D. Bronchodilation Q2. A farmer presented with pin point pupil and increase in secretions. Likely poisoning is A. Organophosphate poisoning B. Dhatura poisoning C. Opioid poisoning D. Atropine poisoning Q3. Topical antiglaucoma drug dorzolamide act by which of the following mechanism of action? A. Carbonic anhydrase inhibition B. Beta blockade C. Alpha agonist D. Prostaglandin analog Q4. A patient with history of snake bite presented in emergency with symptoms of fatigue and irritability. Ten vials of antivenom were administered intravenously but the patient is still having difficulty in swallowing, ptosis and respiratory distress. What should be the next line of management? A. Atropine and neostigmine B. Nebulizer with salbutamol C. IV hydrocortisone D. Antihistamines Q5. A patient on treatment of myasthenia gravis presents with increasing muscle weakness. Which of the following drug is used to differentiate myasthenia gravis from cholinergic crisis? A. Edrophonium B. Pilocarpine C. Atropine D. Pyridostigmine Q6. A 20 year old boy was brought to emergency room after consuming some unknown substance. The patient was sweating profusely, saliva was drooling from mouth and tears were present. The boy had involuntary urination and diarrhea. On examination, the heart rate was 58 beats per minute and blood pressure was 80/60 mm Hg. Which of the following is the drug of choice for treatment of this patient? A. Atropine B. N-acetylcysteine C. Naloxone D. Physostigmine Q7. A study was conducted to see the effect of different drugs on isolated mammalian intestinal tissue in Dale’s organ bath. The following graph is obtained. Which of the following is the likely drug? A. Acetylcholine B. Barium chloride C. Adrenaline D. KCl Q8. An experiment on dog blood pressure was done by adding different drugs. The drugs added and the effects are as shown in the given figure. This experiment is done to demonstrate the Answers 1. - A 2. - A 3. - A 4. - A 5. - A 6. - A 7. - C 8. - B
  • 21.
    21 Pharmacology Answers 19. - B 20.- C A. Muscarinic action of ACh B. Nicotinic action of ACh C. Potentiation of ACh D. Antagonistic action of ACh Q9. After eating an unknown plant, A child presented to emergency in comatose state. The pupils were dilated and skin was dry. Body temperature is raised and heart rate is high. These signs and symptoms can occur with the intake of which of the following substance? A. Dhatura B. Poppy seeds C. Mushroom D. Cannabis Q10. Topical atropine is not given in A. Acute congestive glaucoma B. Corneal ulcer C. Malignant glaucoma D. Acute anterior uveitis Q11. All of the following are Side effects of Ritodrine except? A. Hypoglycemia B. Tachycardia C. Hypotension D. Pulmonary edema Q12. Which of the following is the action of dopamine at low doses? A. It increases renal blood flow B. It causes vasoconstriciton C. It has positive chronotropic action D. It causes hypotension Q13. A lady was stung by many bees. She developed breathing difficulty and hypotension. Drug used for treatment of this condition is? A. Adrenaline B. Nor-adrenaline C. Dopamine D. Isoprenaline Q14. A drug addict patient presented with agitation and ulceration on skin. The patient had severe itching and scratch marks on the body. On examination there is presence of tachycardia, mydriasis and hypertension. Likely substance responsible for these symptoms is? A. Cocaine B. Cannabis C. LSD D. Heroin Q15. Which dose of dopamine act preferably on beta-1 receptors? A. Less than 2 mcg/kg/min B. 2-10 mcg/kg/min C. 10-20 mcg/kg/min D. More than 20 mcg/kg/min Q16. A patient was on metoprolol therapy for hypertension. He was also administered verapamil. Which of the following is likely to happen with above combination therapy? A. Torsades de pointes B. Ventricular tachycardia C. Ventricular fibrillation D. Bradycardia with AV block Q17. A 65 years old patient presented with dribbling of urine with urgency. He was started on prazosin therapy but the patient developed postural hypotension. Which of the following is the better alternative drug for this patient? A. Terazosin B. Tamsulosin C. Timolol D. Phenoxybenzamine Q18. Beta blockers are avoided in all of the following conditions except A. Glaucoma B. Peripheral vascular disease C. Diabetes mellitus D. COPD Q19. Hypertension and pulmonary edema associated with scorpion sting is managed by: A. Carvedilol B. Prazosin C. Spironolactone D. Phentolamine Q20. Which of the following is a contraindication to the use of Beta Blockers? A. Glaucoma B. Tachycardia C. Bronchial asthma D. Hypertension 9. - A 10. - A 17. - B 18. - A 11. - A 12. - A 13. - A 14. - A 15. - B 16. - D
  • 22.
    22 Cerebellum Quick RevisionNotes Q21. A known patient of bronchial asthma was started on treatment with an anti-glaucoma drug. During the course of treatment, asthma worsened. Which drug is likely responsible for these symptoms? A. Timolol B. Brimonidine C. Latanoprost D. Pilocarpine Q22. A patient had symptoms of redness and photophobia. On examination, cells were present in anterior chamber with keratic precipitates. Intraocular pressure was measured to be 38 mm Hg. Which of the following anti-glaucoma drug should be avoided? A. PG analogues B. Beta blockers C. Mannitol D. Carbonic anhydrase inhibitors Q23. Drug capable of causing ocular hypotension with apnoea in infants is: A. Acetazolamide B. Latanoprost C. Brimonidine D. Apraclonidine Q24. Anti-glaucoma drug that acts by increasing uveoscleral outflow is A. Latanoprost B. Timolol C. Pilocarpine D. Dorzolamide Q25. A patient with bronchial asthma presents with raised intraocular pressure. Treatment of open angle glaucoma in this patient is A. Latanoprost B. Alprostadil C. Gemeprost D. Carboprost Q26. Which anti-glaucoma drug acts by increasing trabecular outflow? A. Netarsudil B. Timolol C. Acetazolamide D. Brimonidine Answers 21. - A 22. - A 23. - C 24. - A 25. - A 26. - A
  • 23.
    Chapter - 3Autacoids - Have autocrine effects [Local effects] - Based on chemical Structure Peptide Autacoids → Angiotensin → Bradykinin Amine Autacoids →Histamine → 5-HT Lipid Autacoids →Prostaglandins →Leukotrienes →Thromboxane HISTAMINE Receptors Location Action Blockers H1 CNS Bronchus Allergy Stimulates RAS Promote wakefulness First and second Generation Drugs H2 Stomach Secrete Acid Ranitidine Cimetidine H3 PreSynaptic BRAKE H3 Inverse Agonist Tiprolisant [Pitolisant] Used for Narcolepsy H4 WBC Chemotaxis H1 Blockers 1st Generation 2nd Generation Cross BBB, cause sedation Do not cross BBB, no sedation Have Anti-cholinergic action → Anticholinergic S/E occur No Anti-cholinergic action Useful for allergy and Possess : Prophylaxis of motion sickness Anti : Akathisia Cholinergic : Common Cold Property : Parkinsonism (Drug induced) Useful only for allergy Promethazine FexofenadineQ • • Terfenadine metabolite Loratidine Cetirizine 5-HT (SEROTONIN) Serotonin Receptors Location Action Drugs Example Uses 5HT1A Presynaptic Brake Agonist BuspironeQ Anxiety 5HT1B/ID BV of Brain Vasoconstriction Agonist Sumatriptan Naratriptan Eletriptan Rizatriptan DOC for Acute Severe Migraine 5HT2A/2C Brain Blockers Clozapine , Olanzapine Atypical Antipsychotics 5HT3 CTZ Emesis Blockers Ondansetron Granisetron Tropisetron Dolasetron PalonosetronQ DOC for vomiting due to Chemotherapy Radiotherapy Post-operativeQ 5HT4 GIT Prokinetic Agonist Cisapride , Mosapride, Prucalopride As prokinetics for GERD
  • 24.
    24 Cerebellum Quick RevisionNotes MIGRAINE:Q → Drug of choice for mild to moderate headache – NSAIDs (Paracetamol, Diclofenac) → Drug of choice for Acute severe attack – Triptans → Other drug for Acute severe migraine – Ergotamine → DOC for prophylaxis of migraine – Propranolol New Drugs for Migraine: 1. Lasmiditan (DITANS) Q • • Stimulates 5HT1F receptor and decreases CGRP release. • • This prevents the vasodilation and neuronal inflammation. • • Effective orally. • • It is recently approved for acute attacks of migraine. • • Advantage over triptans is that it does not induce peripheral vasoconstriction. 2. Monoclonal Antibodies Against CGRP • • Approved for prophylaxis of migraine. • • Given by injectable route. – – Erenumab – – Fremanezumab – – Galcanezumab – – Eptinezumab 3. CGRP Antagonist: (GEPANTS) Q • • Used for acute attack • • Effective orally • • Drugs are – – Olcegepant – – Rimegepant – – Ubrogepant PROSTAGLANDINS 1. General Effects • • Fever • • Pain • • Inflammation 2. Platelets • • TXA2 → Aggregation • • PGl2 → Inhibition of aggregation 3. Heart • • Ductus Arteriosus is kept open by PGE1 • • PDA [Patent ductus Arteriosus] is treated by NSAIDs like – – Aspirin – – Indomethacin – – Ibuprofen (DOC) 4. Uterus • • PGs Contract upper segment of uterus • • Used for abortion (Misoprostol is used) 5. Stomach • • PGE2 protect the stomach from peptic ulcer disease • • For NSAID Induced Peptic Ulcer Disease – – Most specific drug is MisoprostolQ – – DOC is proton pump inhibitors 6. Eye PGF2α → ↑ Uveo scleral outflow → Latanoprost → DOC for Primary Open Angle GlaucomaQ
  • 25.
    25 Pharmacology NON-STEROIDAL ANTI- INFLAMMATORY DRUGS(NSAIDs) COX 1 COX-2 Constitutive Enzyme Present normally at most places Inducible enzyme Present normally in • • Kidney • • Endothelium • • CNS NSAIDS act by inhibiting COX. These may be: Non-Selective COX Inhibitors Selective COX-2 Inhibitors ↑ Risk of PUD Less risk of PUD Non-Selective COX Inhibitors Drugs - Aspirin : Irreversible COX inhibitor (Antiplatelet), ↑Uric acid - Paracetamol : COX - 3 inhibitor, safe in CKD - Ibuprofen : DOC for PDA - Diclofenac : Partial COX-2 selective - Indomethacin: Sedation is adverse effect - Piroxicam : Longest acting NSAID - Nimesulide : Not used in children (hepatotoxic) - Ketorolac : Given IV Selective COX 2 Inhibitors Drugs - Celecoxib - Rofecoxib - Valdecoxib - Parecoxib - Lumiracoxib • • These have lesser risk of causing PUD • • These increase the risk of MI and stroke - Etoricoxib Longest acting - Rofecoxib and Valdecoxib Withdrawn because of MI and stroke - Parecoxib is given by Parenteral route - Lumiracoxib is withdrawn Due to Liver toxicity GOUT It is characterized by increase in serum uric acid. Acute Gout 1. DOC : NSAIDs (except aspirin and paracetamol) 2. Steriods : If NSAIDs do not work 3. Colchicine (Most effective drug):Q - Can cause myopathy and diarrhea - Inhibit granulocyte migration Chronic Gout Three types of drugs can be used in chronic gout. – Drugs decreasing production of uric acid – Drugs increasing excretion of uric acid (Uricosuric agents) – Drugs increasing metabolism of uric acid Proteins / Purines Xanthine Uric acid Excretion 1 2 3 Allantoin Uricase In birds Xanthine oxidase
  • 26.
    26 Cerebellum Quick RevisionNotes 1. ↓ Formation 2. ↑ Excretion AllopurinolQ • • Inhibit xanthine oxidase • • DOC for chronic gout Febuxostat • • Inhibit xanthine oxidase Probenecid Sulfinpyrazone Lesinurad → Plenty of fluids should be taken 3.↑ Metabolism Rasburicase → Recombinant uricase Pegloticase → Long acting uricase These are fastest urate lowering agents for tumor lysis syndromeQ RHEUMATOID ARTHRITIS NSAIDs and Steroids DMARDs or SAARDs • • ↓ Pain and lnflammation • • No effect on disease Progression • • Fast acting • • Slow down the disease progression • • Slow acting 1. Conventional DMARD: Cute and Chloroquine DMARD of choice in pregnancy p Penicillamine Used for Cu poisoning/ Wilson’s disease A Azathioprine G Gold salts L Leflunomide Fastest acting DMARDQ I Inhibitors of JAK Tofacitinib Baricitinib Malika Methotrexate DOC, Needs LFT Monitoring Sherawat Sulfasalazine DOC for ulcerative colitis 2. Biological DMARDs: i. Drugs Inhibiting TNF-a:Q - All are injectable A Adalimumab C Certolizumab E Etanercept Inhibitor lnfliximab Goli Golimumab → ↑ Risk of infections. → Contra-indicated in T.B. and Hepatitis B → Apart from R.A., these drugs can be used for Crohn’s disease as well as Psoriasis ii. IL - 1 Receptor Antagonist:Q ANAKINRA – – A - 1st letter – – KIN - Interleukin – – R - Receptor – – A - Antagonist iii. IL - 6 Receptor Antagonists:Q Tocilizumab → 1st IL- 6 targeted monoclonal Antibody. → Approved for treatment of cytokine release syndrome also. Sarilumab → Used for rheumatoid arthritis S - Six AR - R.A. MAB - Monoclonal antibody iv. Co-stimulation InhibitorsQ • • Abatacept • • Inhibit the interaction of T-cell and Antigen Presenting Cells (APC).
  • 27.
    27 Pharmacology Previous Years Questions Q1.Most specific antiemetic for Chemotherapy induced vomiting is: A. Doxylamine B. Tegaserod C. Granisetron D. Domperidone Q2. Buspirone is a drug used in chronic anxiety. It produce its action by acting on which of the following receptors? A. 5HT1A B. 5HT1B C. 5HT2 D. 5HT3 Q3. A boy is planning to travel by bus. Which of the following drug can be used to prevent motion sickness in this person? A. Promethazine B. Cetrizine C. Loratidine D. Fexofenadine Q4. Drug of choice for prophylaxis of migraine is A. Propranolol B. Imipramine C. Flutamide D. Flunarizine Q5. A young female presented with left sided severe throbbing headache associated with nausea, vomiting, photophobia and phonophobia. Which of the following drug can provide immediate relief to this patient? A. Propranolol B. Sumatriptan C. Topiramate D. Flunarizine Q6. Drug of choice in paracetamol overdose is A. N-acetylcysteine B. Dopamine C. Hydralazine D. Furosemide Q7. A 34 week pregnant female with polyhydramnios presents with labour pain. She was treated with indomethacin earlier. Which of the following can be likely outcome in the baby if delivery occurs at this time? A. Patent ductus arteriosus B. Premature closure of ductus arteriosus C. Patent ductus venosus D. Premature closure of ductus venosus Q8. A 60 year old female with renal disease was admitted for pyelolithotomy. Post operative analgesic of choice in this patient is? A. Diclofenac B. Indomethacin C. Naproxen D. Acetaminophen Q9. Which of the following is the fastest urate lowering therapy in tumor lysis syndrome to prevent renal damage? A. Allopurinol B. Febuxostat C. Rasburicase D. Furosemide Q10. A female patient presented with pain and redness in great toe. Serum uric acid level is 9.6 mg/dL. Apart from prescribing analgesics for relieving pain, the physician prescribed a drug which can decrease the formation of uric acid. Which of the following enzyme is likely to be inhibited by this drug? A. Xanthine oxidase B. Thymidylate synthase C. Phosphpribosyl transferase D. DHFR Q11. Drug inhibiting granulocyte migration is: A. Montelukast B. Cromoglycate C. Colchicine D. Felbamate Q12. Pegloticase is used for treatment of :- A. Ankylosing spondylosis B. CPPD C. Chronic tophaceous gout D. Refractory Rheumatoid arthritis Answers 1. - C 2. - A 3. - A 4. - A 5. - B 6. - A 7. - B 8. - D 9. - C 10. - A 11. - C 12. - C
  • 28.
    28 Cerebellum Quick RevisionNotes Q13. A patient diagnosed with Rheumatoid arthritis was on medications. After 2 years, he developed blurring of vision and was found to have corneal opacity. Which drug is most likely to cause this? A. Sulfasalazine B. Chloroquine C. Methotrexate D. Leflunomide Q14. Tocilizumab is an immunosuppressive drug used for Rheumatoid arthritis. It is a monoclonal antibody against A. IL-6 B. IL-12 C. IL-2 D. IL-3 Q15. A 40 year old male patient presents to hospital with pain in great toe. It was diagnosed to be a case of gout. Which of the following drug increases the excretion of uric acid in urine? A. Colchicine B. Probenecid C. Allopurinol D. Febuxostat Answers 15. - B 13. - B 14. - A
  • 29.
    Diuretics → Causeloss of Na+ & H2 O in urine Classification Based On Site of Action 1. OSMOTIC DIURETICS → Includes mannitol Uses: • • Acute Congestive GlaucomaQ • • Cerebral edema Contra-Indications: • • Cerebral hemorrhage • • Pulmonary edema 2. CARBONIC ANHYDRASE INHIBITORS → Acts on Proximal tubule → Include: Acetazolamide – Given orally or IV Brinzolamide Dorzolamide Indications: Glaucoma (Angle closure glaucoma) Mountain Sickness [DOC]Q Given as eye drops 3. LOOP DIURETICS → Act on thick ascending limb of loop of Henle → Inhibit Na+ K+ 2Cl– symporter → Include Furosemide Torsemide Bumetanide → High ceiling diuretics [High efficacy Diuretics]Q → Effectve in renal failure 4. THIAZIDES → Act on early distal tubule → Inhibit Na+ – Cl– symporter Include Thiazides Thiazide-like diuretics Chlorothiazide Methiazide Polythiazide Indapamide Metolazone Uses • • Hypertension (DOC)Q – – Metolazone is effective in renal failure unlike other thiazides • • Recurrent renal calcium stones • • Diabetes insipidus • • Osteoporosis • • Recurrent renal calcium stones S/E of both Thiazides and Loop diuretics ↓ Na+ ↑ Glucose ↓ K+ ↑ Uric Acid ↓ Mg2+ ↑ Lipids ↓ H+ Note: Loop diuretics cause hypocalcemia whereas thiazides leads to hypercalcemia 5. K+ SPARING DIURETICS → Act on collecting ducts (1) Aldosterone Receptor Antagonists – – Spironolactone – – Epleronone Chapter - 4 Diuretics
  • 30.
    30 Cerebellum Quick RevisionNotes Previous Years Questions Q1. Which of the following drug is a carbonic anhydrase inhibitor? A. Acetazolamide B. Hydrochlorthiazide C. Furosemide D. Mannitol Q2. A 25 year old male presented to emergency with head trauma due to road traffic accident. In hospital, the patient developed seizures. Emergency CT scan revealed widespread cerebral edema. Which of the following is diuretic of choice for cerebral edema in this patient? A. Mannitol B. Spironolactone C. Furosemide D. Hydrochlorthiazide Q3. A 28 year old male went to Ladakh. He developed shortness of breath. Which of the following drug will you use for the treatment of mountain sickness at high altitude? A. Acetazolamide B. Furosemide C. Epleronone D. Salbutamol Q4. Hydrochlorothiazide works by inhibiting A. Na+ Cl- pump in DCT B. Na+ Cl- pump in PCT C. Na+ K+ 2 Cl- pump in descending limb of loop of Henle D. Na+ K+ 2 Cl- pump in ascending limb of loop of Henle Q5. At a high altitude of 3000m, a person complains of breathlessness. All of the following can be used for management of this person except A. Intravenous digoxin B. Oxygen supplementation C. Immediate descent D. Acetazolamide Q6. Mannitol is used in the management of: A. Congestive Cardiac Failure B. Acute Congestive Glaucoma C. Acute Renal Failure D. Pulmonary edema Q7. A patient of chronic liver cirrhosis presents with ascites. Which of the following is the best diuretic to be used in this patient? A. Eplerenone B. Chlorthiazide C. Furosemide D. Triamterene Q8. Which of the following diuretic acts on the site X shown in the figure? A. Furosemide B. Hydrochlorthizide C. Spironolactone D. Acetazolamide Answers 1. - A 2. - A 3. - A 4. - A 5. - A 6. - B 7. - A 8. - B (2) Epithelial Na+ channel Blockers – – Triamterene – – Amiloride These drugs cause ↓ Na+ & H2 O → Diuresis ↑ K+ → Hyperkalemia ↑ H+ → Metabolic AcidosisQ P → Potassium sparing Diuretics A → Amiloride S → Spironolactone → Cause Gynaecomastia T → Triamterene E → Epleronone → Do not cause Gynaecomastia Uses: - DOC for Conn’s Syndrome - DOC for Edema in Cirrhosis - DOC for Resistant hypertension
  • 31.
    Chapter - 5Cardiovascular System CONGESTIVE HEART FAILURE In low output CHF, heart is not able to pump enough blood. It results in accumulation of fluid in various parts of body. ACUTE (DECOMPENSATED) CHF Aim of treatment of Acute CHF 1. ↓ FLUID → Loop Diuretics 2. ↑ PUMPING → Inotropics A. b1 Agonists • • Dopamine • • Dobutamine • • Nor-adrenaline • • Isoprenaline B. Phosphodiesterase Inhibitors [Inodilators] • • Inamrinone • • Milrinone CHRONIC CHF (COMPENSATED) Aim of Treatment in Chronic CHF 1.↓ Work 2.↓ Fluid 3.↓ LVH [Cardiac Remodeling] 4.Inotropic action Drugs Used In Chronic CHF → 4’D’ are used Diuretics Dilators Decrease LVH Digoxin 1. ↓ Work → Vasodilators Venodilators Arteriolar dilators Veno + Arteriolar Dilators ↓ Preload Nitrates ↓ Afterload Hydralazine ↓ Preload and ↓ Afterload Na Nitroprusside ACE inhibitors Angiotensin receptor blockers 2. ↓ Fluid → Loop Diuretics 3. ↓ LVH [Cardiac Remodeling] It results due to excessive aldosterone → These drugs decrease mortality in CHFQ A. Beta Blockers B. ACE inhibitors C. Angiotensin Receptor Blockers D. Aldosterone Antagonists
  • 32.
    32 Cerebellum Quick RevisionNotes 4.  Contractility (Ionotropics) DIGOXIN → Only inotropic drug that can be given Orally MOA in CHF → Inhibit Na+ - K+ pump that ↑ intracellular calcium and thus inotropic action. MOA in Atrial Fibrillation → Vagomimetic effect lead to ↓ AV conductionQ Adverse Effects 1. Nausea, Vomiting [MC] 2. Arrhythmias MC arrhythmia → Ventricular bigeminyQ Most specific → NPAT with AV BlockQ 3. Xanthopsia / Yellow VisionQ 4. Gynaecomastia Drugs Causing Gynaecomastia DI : DIgoxin S : Spironolactone C : Cimetidine K : Ketoconazole O : Oestrogens Factors ↑ Digoxin Toxicity Metabolic Drugs ↑ Ca2+ ↓ K+ ↓ Mg2+ Quinidine Verapamil Amiodarone Thiazides and Clarithromycin Mx of Digitalis ToxicityQ 1. Correct the cause 2.DOC for Digitalis induced arrhythmias → Lignocaine 3.Digibind for Severe poisoning ANGINA PECTORIS Drugs for Angina Pectoris I. Nitrates II. Calcium Channel Blockers III. Beta Blockers IV. Potassium Channel Openers I. Nitrates Mechanism of action: Nitrates ↓ Nitric oxide ↓ Guanylate cyclase ↓ ↑ cGMP ↓ Vasodilation (Veins >> Arteries) → MOA of nitrates in classical angina - ↓ Preload → MOA of nitrates in variant angina → Dilation of coronary arteriesQ Drugs • • Glyceryl Trinitrate / Nitroglycerine [GTN/ NTG] • • Isosorbide Dinitrate [IDN] • • Isosorbide Mononitrate [IMN] • • Penta Erythrital Tetra Nitrate [PETN] • • Amyl Nitrite [AN] Nitrates ↓ NO ↓ ↑ cGMP Degraded ↓ VD ↓ Hypotension Nitrates should not be given with Sildenafil [Risk of Severe hypotension]Q Sildenafil PDE
  • 33.
    33 Pharmacology GTN/NTG and IDN • •DOC for acute attack of angina • • Have high 1st pass metabolism • • Sublingual route preferred → IMN has minimum 1st pass metabolism → Longest acting → PETN → Shortest acting → AN → Amyl nitrite is used in cyanide poisoning as an antidote → Tolerance occurs, if nitrates are continuously present in blood → To avoid tolerance, 6-8 hours of Nitrate Free Period should be maintainedQ ll. L-Type Calcium Channel Blockers → DOC for variant angina - CCB like verapamil and diltiazem → Dipines are not used because they can worsen angina due to reflex tachycardiaQ III. Potassium Channel Opener NICORANDIL → NO Releaser + K+ channel openerQ IV. Beta Blockers – – Useful in classical angina (Act by ↓ HR) – – Contra-indicated in variant angina New Drugs for Angina Pectoris 1. Bradycardiac Agent → IvabradineQ Ivabradine inhibit Na+ channel [Funny current] in SA node → S/E → ↓ Visual acuity (Phosphenes) 2. Rho Kinase Inhibitor → FasudilQ 3. Metabolic Modulators → Fatty Acids require more oxygen for same energy production than glucose → Metabolic Modulation → Making heart to utilize glucose instead of fatty acids DrugsQ 1. Trimetazidine 2.Ranolazine → Main mechanism of ranolazine is now assumed to be inhibition of Late Inward Na channels. MYOCARDIAL INFARCTION (MI) Non-STEMI M → Morphine O → Oxygen N → Nitrates A → Aspirin STEMI S → Streptokinase O → Oxygen N → Nitrates A → Aspirin M → Morphine HYPERTENSION 1. First Line Drugs for Hypertension without any compelling Indications are: A – ACE inhibitors and ARBQ B – Beta Blockers (Not considered first line drugs now) C – Calcium channel blockers D – Diuretics ACE Inhibitors • • Name ends with pril C → Cough A → Angioedema P → Prodrugs except captopril & Lisinopril T → Taste alteration [Dysgeusia] O → Orthostatic / Postural hypotension [max with captopril]Q P → C/l in Pregnancy R → C/lin B/L Renal Artery StenosisQ I → C/I in Increased K+ L → Lower the risk of Diabetic Nephropathy ARBs [Angiotensin (AT1) Receptors Blockers] - Name ends with ‘SARTAN‘ - All points about ACE inhibitors apply to ARB also, except that these do not cause cough and angioedema and ARB are not pro-drugs. - Telmisartan is a PPAR-g agonist and can reverse insulin resistanceQ
  • 34.
    34 Cerebellum Quick RevisionNotes 2. DOC in special situationsQ Condition DOC HTN in pregnancy Oral Labetalol > Methyldopa HTN Emergency in pregnancy IV Labetalol HTN Thiazides HTN Emergency Nicardipine > Nitroprusside Resistant Hypertension (Resistant to minimum 3 drugs including thiazides) Spironolactone PULMONARY HYPERTENSION Intravenous Vasodilator Testing (on giving IV CCB, pulmonary artery pressure decreases) → If positive, DOC → CCBQ → If negative, DOC → Endothelin antagonistQ DRUGS USED IN PULMONARY HYPERTENSION 1. Calcium channel blockers: DHPs like amlodipine are DOC if IV vasodilator testing is positive (in < 5% cases) 2. Endothelin antagonists: Bosentan, ambrisentan like drugs are DOC for pulmo- nary hypertension 3. PDEI [Phosphodiesterase Inhibitors] → Sildenafil, Tadalafil 4. Prostaglandins PGI2 → lloprost 5. Selexipag → Prostacylin agonist → Can be given orally SELE → Selective XI → Non injectable [Oral] P → PGI2 AG → Agonist ANTI-ARRHYTHMIC DRUGS Vaughan Williams Classification → Based on predominant mechanism of action Class I → Na+ Channel Blockers Class II → b Blockers Class III → K+ channel blockers Class IV → Ca2+ Channel Blockers Class V → Others Class I DrugsQ → Na+ Channel blockers → ↓ Slope of Phase 0 Class Effect on K+ channel Effect on APD QT interval 1a Blocker ↑ ↑QT 1b Opener ↓ ↓QT 1c No effect - No effect Class 1a Drugs Class 1b Drugs Class 1c Drugs Quinidine Procainamide Lignocaine Phenytoin Tocainide Encainide Flecainide Cause QT Prolon- gation Used only for Ven- tricular arrhythmia Class II → Beta BlockersQ → Used in Tachyarrhythmias Class III → K+ Channel Blockers B → Bretylium I → Ibutilide N D → Dofetilide, Dronedarone A → Amiodarone S → Sotalol → Sotalol has both Class III [Major] & class II Actions
  • 35.
    35 Pharmacology AMIODARONE → Longest acting[t1/2 → > 3wks] anti arrhythmic drug → MOA 1. Na+ channel Blocker 2. Beta-Blocker (Non-competitive) 3. K+ channel Blocker [Main action] 4. Calcium channel blocker → Adverse effect of amiodaroneQ The Thyroid (hypo/hyper) (40% iodine is present in amiodarone) Periphery of Peripheral neuropathy My Myocardial depression Lung Lung fibrosis Liver Liver toxicity Cornea is Corneal deposits Photosensitive Photosensitivity (Rash on exposure to sun) (Bluish: Blue man syndrome) Class IV → L-Ca2+ Channel Blockers – – Verapamil – – Diltiazem – – DHPs [Not Used] → Used in Tachyarrhythmias →Shouldnotbecombinedwithβblockers[RiskofSevere Bradycardia and AV Block] Class V Digoxin - Used for AF (in patients with CHF) Atropine - DOC for Bradycardia & AV block Adenosine -Shortestactingantiarrhythmicdrug(t1/2 < 10s) - DOC for PSVTQ ANTI-DYSLIPIDEMIC DRUGS 1. Statins MOA 1.Inhibit HMG-COA Reductase (Rate limiting enzyme in cholesterol synthesis)Q 2.Compensatory ↑ of LDL - R 3.Cholesterol is taken from blood 4.↓ Serum cholesterol Examples – – Atorvastatin – – Rosuvastatin [Longest Acting] – – Pravastatin – – Simvastatin Important Points A. Statins have maximum LDL – Cholesterol lowering potential B. Given at late evening/night • • Atorvastatin & Rosuvastatin are long acting, can be given at anytime of the day • • Rosuvastatin is longest acting statin.Q C. Adverse EffectsQ – – Myopathy → Risk further ↑ with Fibrates and enzyme inhibitors like clarithromycin and erythromycin. – – Hepatotoxicity – – Hyperglycemia: ↑ Risk of new onset DM. D. Pleiotropic EffectsQ These are additional benefits apart from improving lipid profile. PL → Plaque Stabilization E → ↓ Endothelial dysfunction I → ↓ Inflammation O → ↓ Oxidative Stress TR→ ↓ Thrombosis Opic
  • 36.
    36 Cerebellum Quick RevisionNotes 2. Other Drugs Fibrates Clofibrate Fenofibrate • Max TG lowering potential • S/E → Gall StonesQ Ezetimibe Inhibit absorption of cholesterol from intestine Usually combined with statins BABA Cholestyramine Colestipol DOC in pregnancy and children S/E → ↑ TG Niacin Vitamin B3 Max. HDL - C increasing potential Compliance limiting S/E → Itching & flusing HyperuricemiaQ Hepatotoxicity 3. New Drugs A. PCSK - 9 (Pre Protein ConvertinSubtilisinKexin Type 9) InhibitorsQ • • PCSK-9 binds to LDL - receptors and take it to lysosomes that result in breakdown of LDL receptors. • • Thus PCSK 9 inhibitors prevent breakdown of LDL receptors. When more LDL receptors are present, they can take up more LDL-cholesterol from blood. • • So, we can use these drugs as hypolipidemic drugs. • • Alirocumab and Evolocumab are monoclonal antibodies against PCSK-9 B. MTP (Microsomal Triglyceride Triglyceride Transport Protein) Inhibitors • • Triglycerides are packed in VLDL by MTP • • Drug inhibiting MTP is Lomitapide C. Evinacumab • • Monoclonal antibody against ANGPTL1 (Angiopoietin Like Protein 3) • • It acts independent of LDL-receptor density.
  • 37.
    37 Pharmacology Previous Years Questions Q1.A hypertensive patient has grade 4 renal failure and GFR less than 30 mL/min. The physician wants to prescribe a thiazide diuretic. Which is the best drug for this patient? A. Hydrochlorthiazide B. Chlorthalidone C. Metolazone D. Indapamide Q2. A patient with chronic stable angina presents with pedal edema, breathlessness and other symptoms of heart failure. Which of the following drug can increase longevity in this patient? A. Nifedipine B. Digoxin C. Lisinopril D. Torsemide Q3. Drug of choice for treatment of digoxin induced ventricular arrhythmias is? A. Atropine B. Lidocaine C. Amiodarone D. Procainamide Q4. A patient on digoxin therapy accidently consumed 8 tablets of digoxin 0.25 mg. Two hours later, he presented to emergency with heart rate of 54 bpm and ECG evidence of third-degree AV block. What is the immediate management of this patient? A. Digoxin immune Fab B. Lignocaine C. Phenytoin D. DC cardioversion Q5. A patient on digoxin therapy and had a level of 1 ng/ ml. He was receiving several other drugs and presented 2 months later with flattening of T waves in ECG. Now the plasma level of digoxin is 3.8 ng/ml. Which of the following drug is likely to be responsible? A. Triamterene B. Atenolol C. Clarithromycin D. KCl Q6. All of the following drugs are indicated in the treatment of NSTEMI except A. Clopidogrel B. Aspirin C. Streptokinase D. Prasugrel Q7. Which of the following is a K+ Channel Opener? A. Ranolazine B. Nicorandil C. Verapamil D. Quinidine Q8. Which of the following is a late inward sodium channel blocker? A. Ivabradine B. Ranolazine C. Trimetazidine D. Fasudil Q9. Which of the following drug acts at the site marked by arrow as shown in the diagram A. Aliskiren B. Ramipril C. Losartan D. Spironolactone Answers 1. - C 2. - C 3. - B 4. - A 5. - C 6. - C 7. - B 8. - B 9. - B
  • 38.
    38 Cerebellum Quick RevisionNotes Q10. Which of the following antihypertensive drug is avoided in patients with high serum uric acid levels? A. Hydrochlorothiazide B. Enalapril C. Prazosin D. Atenolol Q11. A 34 weeks pregnant lady presented with seizures. Her blood pressure is 200/110 mm Hg. Which drugs should be used for the treatment of this patient? A. Oral Labetalol B. IV labetalol plus magnesium sulphate C. IV Lorazepam D. IV Enalapril Q12. Drug used for treatment of pregnancy induced hypertension is A. Alpha methyl dopa B. Lisinopril C. Hydralazine D. Telmisartan Q13. A 56 year old patient who is a known case of hypertension was being treated with antihypertensive drugs. He is having chronic cough since 2 weeks. He was started on antimicrobials but cough did not resolve. Which of the following antihypertensive drug may induce chronic cough in this patient? A. Lisinopril B. Minoxidil C. Propranolol D. Amlodipine Q14. A 26 year old female came to hospital for pre- conceptional counselling. Patient is a known hypertensive compliant to drug therapy. Which of the following drugs will you advise to stop? A. Methyl dopa B. Labetalol C. Lisinopril D. Nifedipine Q15.Identify the correct match regarding the drug and its adverse drug reaction? A. Hydralazine: Heart failure B. Verapamil: Constipation C. Aliskiren: Hypokalemia D. Atenolol: Hemolytic anemia Q16. Resistant hypertension is defined as inability to attain goal blood pressure inspite of the concurrent use of 3 antihypertensive agents of different classes prescribed at optimal doses including A. Alpha blockers B. Diuretics C. Reserpine D. Alpha methyl dopa Q17. A 45 year old patient presented with the symptoms shown in image below. Patient is a known hypertensive and was taking some antihypertensive drug. Which of the following drug is the likely cause of this condition? A. Lisinopril B. Clonidine C. Nifedipine D. Timolol Q18. Which of the following drug should be stopped in a patient with hyperkalemia? A. Losartan B. Furosemide C. Amlodipine D. Hydrochlorthiazide Q19. A patient presents with grade 2 pulmonary artery hypertension. Vaso-reactive stimulation test is negative. Which is the most preferred initial management of this patient? A. Epoprostenol B. Amlodipine C. Alprostadil D. Ambrisentan Answers 10. - A 11. - B 12. - A 13. - A 14. - C 15. - B 16. - B 17. - A 18. - A 19. - D
  • 39.
    39 Pharmacology Q20. A 65-year-oldman comes to OPD with history of fall. He is hypertensive with history of atrial fibrillation and is presently on captopril, atenolol, aspirin and amiodarone. He presents with the following finding as shown in the image. What is the most probable diagnosis? A. Silver toxicity B. Lupus pernio C. Amiodarone induced skin lesion D. Captopril toxicity Q21. Which of the following antiarrhythmic drug is contraindicated in a patient with interstitial lung disease? A. Amiodarone B. Sotalol C. Quinidine D. Lignocaine Q22. The figure below shows the effect of a drug on the action potential of heart as shown by arrow. Which of the following drug is likely to produce this effect on action potential? A. Quinidine B. Lignocaine C. Esmolol D. Tocainide Q23. Which of the following drug should be avoided in a patient on rosuvastatin therapy? A. Clarithromycin B. Oxycodone C. Rivaroxaban D. Adalimumab Q24. Which of the following hypolipidemic drug acts by inhibition of PCSK-9? A. Atorvastatin B. Evolocumab C. Ezetimibe D. Lomitapide Q25. Which of the following anti-dyslipidemic drugs can result in gall stones? A. Statins B. Bile acid sequestrants C. Niacin D. Fibrates Answers 20. - C 21. - A 22. - A 23. - A 24. - B 25. - D
  • 40.
    PITUITARY HYPOTHALAMIC SYSTEM AnteriorPituitary Hypothalamic control Growth Hormone [GH] GHRH [GH Releasing Hormone] GHIH [GH Inhibiting Hormone] Thyroid Stimulating Hormone Thyrotropin Releasing Hormone Adreno corticotropic Hormone Corticotropin Releasing Hormone Gonadotropins GnRH [Gn Releasing Hormone] Prolactin Prolactin Inhibiting Hormone 1. Growth Hormone Inhibiting Hormones [GHIH] – – It is also known as Somatostatin SOMA TOSTATIN USESQ S → Secretory Diarrohea (Carcinoid syndrome, VIPoma) O → Oesophageal Varices M → Malignancy [Insulinoma, Glucagonoma] A → Acromegaly → Any drug ending with “tide” is peptide. → Any endogenous substance ending with “in” is a peptide e.g; Somatostatin Vasopressin Oxytocin → Peptides cannot be given orally Somatostatin → Short acting therefore not used Octreotide → Long-acting somatostatin derivative → Given by SC route 2. Prolactin Inhibiting Hormone [PIH] = Dopamine [DA] → DA acts through D2 Receptors → Dopamine D2 Agonists decrease prolactin Examples Bromocriptine Cabergoline [Long acting] Uses of Dopamine AgonistsQ Dopamin - Diabetes mellitus type 2 (Bromocriptine) Agonists - Acromegaly (by decreasing GH) Suppress - Suppression of lactation. Plasma - Parkinsonism (Bromocriptine can be used) Prolactin - Hyperprolactinemia Drugs for Acromegaly A. Decreased GH release – – Octreotide – – Cabergoline – – Bromocriptine B. GH receptor antagonist – – Pegvisomant 3. Gonadotropin Releasing Hormone [GnRH] Pulsatile Fashion ↓ ↑ Gonadotropins ↓ ↑ Estrogen ↑ Progesterone ↑ Testosterone Continuous Fashion (Non-pulsatile manner) ↓ ↓ Gonadotropins ↓ ↓ Estrogen ↓ Progesterone ↓ Testosterone Indications of GnRH Pulsatile manner Continuous Fashion 1. Anovulatory infertility 2. Hypogonadotropic hypogonadism 3. Delayed Puberty 1. Carcinoma prostate 2. Endometriosis 3. Precocious Puberty GnRH AgonistsQ 1. Leuprolide 2. Nafarelin (nasal route) 3. Goserelin 4. Busurelin 5. Histarelin → Not effective orally (Mostly given by subcutaneous route) → Flare up Reaction: When these are given in continuous Chapter - 6 Endocrine system
  • 41.
    41 Pharmacology manner, for initialfew days, there is aggravation of disease GnRH AntagonistsQ 1. Cetrorelix 2. Ganirelix 3. Abarelix 4. Degarelix → No Flare up reaction → But they do not ↑ sex hormones (Used only to ↓ sex hormones) → Not effective orally ELAGOLIX → Recently approved oral GnRH antagonist → Approved for pain due to Endometriosis POSTERIOR PITUITARY → Secretes two main hormones • • Oxytocin • • Vasopressin Oxytocin – – Main function is to contract the uterus • • DOC for augmentation of labour • • DOC for postpartum hemorrhage – – Other function is ejection of milk • • DOC for Breast engorgement Vasopressin – – Also known as anti diuretic hormone (ADH) Vasopressin Receptors V1 Receptor – – Present on BV – – Cause vasoconstriction V2 Receptor – – Present on kidney – – ↓ Urine. Vasopressin Receptor Agonists – – V1 agonist is terlipressin • • DOC for esophageal varicesQ – – V2 agonist is desmopressin • • DOC for neurogenic (central) diabetes insipidus (Given by nasal route)Q Vasopressin Receptor Antagonists – – VAPTANS: VAsoPressin ANTagonistsQ – – Examples Conivaptan - Given via Intravenous route Tolvaptan - Given via Oral route – – Used for SIADH THYROID Hypothyroidism – – DOC is L-thyroxine (T4) – – Started at 25 mcg daily – – Gradually the dose is increased Hyperthyroidism 1. Thyroid Peroxidase Inhibitors (Thioamides) Carbimazole (Prodrug) Methimazole (Active) Propyl Thio Uracil (PTU) → Crosses placenta easily → Less crossing of Placenta → DOC for all patients except in 1st trimester of pregnancy → DOC in 1st trimesterQ → Can cause choanal atresia and aplasia cutis in developing fetusQ → Lesser chance 2. Secretion Inhibitors • Nal • Kl • Lugol’s Iodine → Fastest acting anti-thyroid drugs. → Given preoperatively: – – To make the gland small, firm and less vascular – – To reduce the blood loss during surgery.
  • 42.
    42 Cerebellum Quick RevisionNotes 3. Radioactive iodine or I131 → C/I in pregnancyQ → Cause irreversible hypothyroidism → Physical t ½ is 8 days ENDOCRINE PANCREAS Secretes Action Uses α cells Glucagon ↑ Blood Sugar Hypoglycemia β cells Insulin Amylin ↓ Blood Sugar Diabetes mellitus δ cells Somatostatin ↓ Insulin ↓ Glucagon Islet cell tumors GLUCAGON Uses 1. Hypoglycemia → Acts by Glycogenolysis → Not useful in hypoglycemia caused by • • Starvation • • Alcohol induced hypoglycemia 2. Beta- Blocker Poisoning – Glucagon is DOCQ – Acts by stimulating glucagon receptors on heart INSULIN Indications 1. All patients of type 1 DM 2. Uncontrolled patients of type 2 DM 3. Diabetes in pregnancy 4. Diabetic Ketoacidosis Routes of Administration 1. Sub - cutaneous route: – – MC route (because self-administration is possible with this route) – – All insulin preparations can be given by subcutaneous route. – – Site of administration • • Entire abdomen except area around umbilicus (thickness of skin is not uniform, soinsulin absorption is affected) • • Anterior thigh • • Lateral thigh • • Arm 2. Intravenous route: • • Only regular insulin can be given • • So, insulin of choice in diabetic Ketoacidosis → Regular insulin 3. Inhalational route: Afreeza → Short acting insulin → So, should be given before every meal INSULIN ANALOGUES Rapid acting Ultra-Long Acting • • LISPRO • • ASPART • • GLULISINE • • GLARGINE • • DETEMIR • • DEGLUDEC (Longest Acting)Q - These are peakless insulins - These have low risk of hypoglycemia Side Effects 1. Hypoglycemia 2. HypokalemiaQ ORAL ANTI DIABETICS DRUGS 1. Insulin Secretagogues (Act by ↑ Insulin secretion)Q – – These drugs secrete insulin and thus can cause hypoglycemia Sulfonylureas Meglitinides 1st Generation Nateglinide Repaglinide Chlorpropamide Tolbutamide 2nd Generation Glipizide Gliclazide Glibenclamide Drugs ending with “IDE” can cause - hypoglycemiaQ
  • 43.
    43 Pharmacology 2. Drugs Actingby Other Mechanisms A. Metformin Adverse effects 1. Megaloblastic Anemia 2. Lactic acidosis Risk of lactic acidosis further ↑, if there isQ – – Liver disease (Gluconeogenesis cannot occur) – – Renal disease (Lactic acid produced cannot be excreted) – – Any condition predisposing to hypoxia (e.g.; Shock, COPD) Thus, metformin is C/I in these patients. Indications → Metformin is DOC for Type 2 DM because: – – No risk of hypoglycemia – – Max. reduction in HbA1cQ – – Can cause weight loss or weight neutral (No weight gain) B. Glitazones E.g. Troglitazone Rosiglitazone Pioglitazone Mechanism ActbystimulatingPPAR-ꝩ → ReversalofInsulinResistance Adverse Effects 1. Hepatotoxic → Max. hepatoxicity → Troglitazone [withdrawn]Q → Rosiglitazone and Pioglitazone require LFT monitoringQ 2. Na+ and water Retention → Avoid in CHF and HTNQ 3. Predispose to osteoporotic fractures. 4. ↑ Risk of Ml by rosiglitazone 5. ↑ Risk of urinary bladder carcinoma by PioglitazoneQ C. Acarbose → Act by inhibiting the intestinal absorption of carbohydrates (blood sugar decreases) → Does not cause hypoglycemia → Flatulence → MC side effect → C/I in lnflammatory bowel diseaseQ • • Ulcerative colitis • • Crohn’s disease NEW ANTIDIABETIC DRUGS 1. Incretin – Mimetics → Incretins are normal physiological substances which are released in GIT after food intake that stimulate the release of insulin. → Most important endogenous incretins are GLP (Glucagon like peptide) and GIP (Glucose stimulated insulinotropic polypeptide) → Functions of Incretins: – – Increase insulin release – – Decrease gastric motility → GLP is metabolized by DPP-4 and becomes inactive A. GLP analogues: → Given subcutaneously (Cannot be given orally since these are peptides) GLP-1 analogues : Used for type 2 DMQ – – Exenatide – – Liraglutide GLP-2 analog : Used for short bowel syndromeQ – – Teduglutide Side effects – – Acute pancreatitis (Major side effect) – – Increased risk of Medullary carcinoma of Thyroid
  • 44.
    44 Cerebellum Quick RevisionNotes B. DPP - 4 inhibitors: a. Sitagliptin b. Vildagliptin c. Alogliptin d. Linagliptin → Gliptins are oral anti - diabetic drugs. – – Pancreatitis is the major adverse effect – – Gliptins are contraindicated in renal failure except Linagliptin which is safe in renal failure 2. SGLT-2 Inhibitors: → Glucose is freely filtered by glomerulus but the clearance of glucose in urine is negligible. → Because the reabsorption takes place in proximal tubule by sodium glucose transporter (SGLT-2) → SGLT-2 inhibitors stop the reabsorption of glucose in PT resulting in glucosuria. Drugs areQ – – Canagliflozin – – Dapagliflozin – – Empagliflozin – – Ertugliflozin – – Most common side effect of SGLT-2 Inhibitors is Urinary Tract infections – – SLGT-2 inhibitors provide cardiovascular benefits. These are approved for treatment of CHF. 3. Amylin Analogs: → Amylin is secreted form β - cells of pancreas. → Function of amylin is to ↓ blood sugar. → Pramlintide is an amylin analogue → It is approved for both type 1 and 2 diabetes. 4. BromocriptineQ → Decreases insulin resistance and it has been recently approved for type 2 diabetes treatment. → Given in small dose and taken at early morning on awakening. ADRENAL Adrenal Medulla Adrenal Cortex → Secretes – – Adrenaline – – Nor-Adrenaline – – Dopamine → Secretes – – Glucocorticoids – – Mineralocorticoids Mineralocorticoids Aldosterone → Major endogenous Mineralocorticoid Actions – Retain Na+ and water – Remove K+ and H+ Glucocorticoids Hydrocortisone → Major endogenous Glucocorticoid CLASSIFICATION OF DRUGS Glucocorticoids Mineralocorticoids Short Acting (<12 hours) Cortisone Hydrocortisone Aldosterone Fludrocortisone DOCA Intermediate Acting (12-36 hours) Prednisone Prednisolone Triamcinolone Long Acting (> 36 hours) Dexamethasone Betamethasone Paramethasone Special PointsQ Property Drug Maximum G activity Dexamethasone Maximum M activity Aldosterone G with max M activity Hydrocortisone M with max G activity Fludrocortisone Selective G Triamcinolone Dexamethasone Betamethasone
  • 45.
    45 Pharmacology Selective M DOCA Note:G means glucocorticoid (anti-inflammatory) M means mineralocroticoid (Na+ and H2 O retaining) Uses of Corticosteroids Antenatal Replacement Other Uses Dexa / Betamethasone for fetal lung maturity (Glucocorticoids increase surfactant production) Acute Adrenal insufficiency / Addisonian crisis [by IV] Chronic Adrenal lnsufficiency / Addison’s disease [by oral] Inflammation Auto immune diseases Transplantation Anticancer therapy Asthma Ante Natal Steroids Total dose Total duration Betamethasone → IM 12 mg every 24 hrs. x 2 DosesQ 24 mg 48 hrs. Dexamethasone → IM 6 mg every 12 hrs. x 4 Doses 24 mg 48 hrs Hypothalamo-Pitutary-Adrenal Axis [HPA Axis] HPA Axis Suppression → Occurs when corticosteroids are given continuously for > 2wks Preventive Measures 1. Stop unnecessary use of steroids 2. If indicated, prescribe them for minimum period preferably < 2wks 3. If indicated for long periods, prescribe them on alternate day – – Long-acting steroids (dexa, beta and paramethasone) are avoided 4. If indicated daily and for longer periods – – Don’t Stop Abruptly – – Tapering should be done Adverse effects Major adverse effect is Cushing syndrome OSTEOPOROSIS Nutritional factors – Calcium – Vitamin D Inhibit osteoclast – Calcitonin – Estrogens – SERMs – Denosumab – Cinacalcet Stimulate osteoblast – PTH 1-34 Drugs used in Osteoporosis Dual action – Strontium – Romosozumab Nutritional Factors – – Calcium is given at a dose of 1200 mg/day (It includes dietary calcium) – – Vitamin D should be given as 800 IU per day Drugs Inhibiting Osteoclast 1. Calcitonin: Given Intranasally 2. BisphosphonatesQ Alendronate Risedronate Zoledronate – – Inhibit osteoclasts – – DOC for Osteoporosis [Osteoporosis due to any reason]
  • 46.
    46 Cerebellum Quick RevisionNotes – – These are indicated for a period of maximum 10 years – – Highly toxic to esophagus Prevention of OesophagitisQ – Take empty stomach – Take with full glass of water – Remain upright for 30 min 3. Estrogen and SERM Decreased estrogen is responsible for post- menopausal osteoporosis Actions of Estrogen Bone → Prevent resorption Blood → ↑ HDL/LDLRatio Breast → ↑ Risk of Carcinoma Endometrium → ↑ Risk of Carcinoma Liver → ↑Clotting Factors→ Thromboembolism → Not preferred for Rx of PM Osteoporosis RaloxifeneQ – – It is selective estrogen receptor modulator – – It has agonist action on ER in bone, blood and liver whereas antagonistic action on breast and endometrium – – Used in post menopausal osteoporosis – – AdditionalBenefits • • ↑ HDL • • ↓ Breast and Endometrial carcinoma risk – – Major S/E → Thromboembolism 4. Denosumab DRUGS STIMULATING OSTEOBLASTS 1. Teriparatide – – Parathyroid hormone contains 84 amino acids (i.e., PTH1-84). – – Full molecule stimulates osteoclast and induces osteoporosis by resorption of bone. – – Teriparatide is a fraction of parathyroid (PTH 1-34) that stimulates Osteoblast and is used for osteoporosis treatment.Q – – Route of administration - Not effective orally (given subcutaneously) – – PTH 1-34 is recommended for maximum 2 years. – – Treatment with PTH 1-34 should be followed by bisphosphonates. DRUGS WITH DUAL ACTIONQ – – These have dual activity of stimulating osteoblast and inhibiting osteoclast – – Strontium ranelate and romosozumab act by dual mechanism – – Romosozumab is a monoclonal antibody against sclerostin ANDROGENS – – 5 α reductase converts testosterone into Dihydrotestosterone (DHT) which works on androgen receptors. Testosterone also can directly work on androgen receptors. – – In treatment of prostatic cancer androgen receptor blockers are commonly used. – – In treatment of BPH and androgenital alopecia (Male pattern baldness): 5 α-reductase inhibitors like finasteride are used. – – On the surface of osteoclast cells, RANK receptors are present. When ligand binds to RANK receptors, it stimulates the resorption of bone. – – Denosumab is a monoclonal antibody against RANK ligand. It inhibits the osteoclastic activity and resorption of bone.Q
  • 47.
    47 Pharmacology – – Both theclass of drugs can cause impotence as an adverse effect ORAL CONTRACEPTIVES 1. COMBINED ORAL CONTRACEPTIVE PILLS → Drugs • • Estrogen - Ethinyl Estradiol • • Progesterone - Levonorgestrel → Dosage • • 1 tablet daily for 21 days from 1st day of menstrual cycle • • No tablet for next 7 days • • To ↑ compliance: 28 tablets strip with 1st 21 tablets contains drug and next 7 tablets contains iron → Missed Tablets If one tablet is missed Take 2 tablet on next day If 2 or more tablets missed • • Discard remaining tablets • • Practice other method of contraception with it. • • Start a fresh from next cycle 2. POP / MINIPILLS – – Used where Combined OCPs cannot be used – – Contains LNG – – OCP of choice in lactationQ 3. EMERGENCY CONTRACEPTIVES A. Combined Oral Contraceptives B. Progesterone Only Pills [LNG] C. Mifepristone Above 3 drugs should be used with in 72 hrs. of unprotected intercourse. D. Ulipristal → Can be used within 120 hours of unprotected intercourse NON CONTRACEPTIVE BENEFITS OF OCPs Other→ ↓ Ovarian cyst [DOC for PCOD] B → ↓ Benign Breast Disease E → ↓ Endometriosis N → ↓ Neoplasia[Endometrial and ovariancancers] E → ↓ Ectopic pregnancy F → ↓ Fibroid I → ↓ Iron deficiency Anemia T → ↓ Premenstrual Tension Syndrome S → ↓ Skeletal Disease [Osteoporosis] ↑ Risk of – – Cervical Ca – – Breast Ca ↓ Risk of – – Endometrial Ca – – Ovarian Ca OCPs POLYCYSTIC OVARIAN DISEASE (PCOD) – – OCPs are DOC for regulating the menstrual cycle in PCOD – – Metformin is used to reverse insulin resistance – – Ovulation inducers are used to induce ovulationQ • • Aromatase inhibitors e.g. letrozole is DOC • • Clomiphene citrate can also be used.
  • 48.
    48 Cerebellum Quick RevisionNotes Q6. A 28 year old female with Graves’ disease was taking medication for hyperthyroidism during pregnancy. She delivered a child with congenital anomaly ‘aplasia cutis congenita’. Most likely drug implicated for this teratogenic effect is? A. Carbimazole B. Levo-thyroxine C. Methylthiouracil D. Liothyronine Q7. Drug of choice for hyperthyroidism in third trimester of pregnancy is A. Carbimazole B. Propylthyouracil C. Sodium iodide D. Radioactive iodine Q 8. A 30 year old female presented with weight gain and cold intolerance. On investigations Value of T3 is 70 ng/dl (reference value 100-200 ng/dl),T4 is 3 mcg/ dl (reference value 5-12 mcg/dl) and TSH is 20 mIU/L (reference value 0.5-5 mIU/L). Which of the following statement is correct regarding the management of this patient? A. Measure T3, T4 and TSH after one month B. Start L-thyroxine (T4) treatment 100 mcg once daily C. Start L-thyroxine (T4) treatment 25 mcg daily and gradually increase D. Start daily L-thyroxine (T4) 100 mcg with Liothy- ronine (T3) 5 mcg Q 9. What is the Drug of choice for Hyperthyroidism in first trimester of Pregnancy? A. Lugol’s iodine B. Methimazole C. Propylthiouracil D. Carbimazole Q 10. Which of the following drug is given pre-operatively to decrease the risk of intraoperative bleeding in a hyperthyroid patient planned for thyroidectomy? A. Potassium iodide B. Propranolol C. Propylthiouracil D. Methimazole Previous Years Questions Q1. A patient was operated for prostate carcinoma and during surgery local metastasis was noted. Which of the following drug this patient should receive? A. Leuprolide B. Desmopressin C. Octreotide D. Tamsulosin Q2. Tolvaptan is used for: A. SIADH B. Central Diabetes Insipidus C. Von Willebrand Disease D. Catecholamine resistant Shock Q3. A patient presents with pituitary tumor that overproduces growth hormone. surgical removal of the tumor was incomplete. What is the first line treatment of this patient? A. Leuprolide B. Octreotide C. Nafarelin D. Goserelin Q4. A 40 year old male presents with protrusion of chin, excessive sweating, impaired glucose tolerance and enlargement of hands and feet? Which of the following drugs is a growth hormone receptor antagonist used to treat this condition? A. Pegvisomant B. Octreotide C. Cabergoline D. Olcegepant Q5. A female presented with galactorrhea. Her urine pregnancy test was negative. MRI of head revealed a large pituitary tumor. Patient refused to undergo surgery for the tumor. Which of the following is the best drug for the treatment of this patient? A. Octreotide B. Bromocriptine C. Promethazine D. Clozapine Answers 1. - A 2. - A 3. - B 4. - A 5. - B 6. - A 7. - A 8. - C 9. - C 10. - A
  • 49.
    49 Pharmacology Q 16. Whichof the following drug is given to mother delivering premature baby for fetal lung maturation? A. Aspirin B. Dexamethasone C. Magnesium sulfate D. Depot medroxy progesterone acetate Q 17. A patient presented with the following features after chronic intake of a drug for several years. Which is the likely drug person has consumed? A. Paracetamol B. Prednisolone C. Phenytoin D. Metformin Q 18. What is the prenatal dose of dexamethasone given for lung maturation in premature infants ? A. 6 mg 2 doses 12 hours apart B. 12 mg 2 doses 24 hours apart C. 6 mg 4 doses 12 hours apart D. 6 mg 4 doses 24 hours apart Q 11. A 70 year old patient has diabetes mellitus and hypertension. He presents with late stage chronic kidney disease. Which of the following anti-diabetic drugs require least dose modification in renal disease? A. Sitagliptin B. Vildagliptin C. Linagliptin D. Saxagliptin Q 12. A 50 year old patient of type 2 diabetes mellitus was controlled on oral hypoglycemic drugs. This patient presented to hospital with profuse sweating and dizziness. There was presence of hypoglycemia. Which among the following drugs can result in hypoglycemia in this patient? A. Metformin B. Voglibose C. Vildagliptin D. Glipizide Q 13. Which of the following anti-diabetic drugs is associated with increased risk of fractures in a female with osteoporosis? A. Canagliflozin B. Rosiglitazone C. Voglibose D. Rapaglinide Q 14. Mechanism of action of exenatide in diabetes mellitus is A. It is analogue of GLP released from gut and in- crease glucose dependent insulin secretion B. It is DPP-4 inhibitor and result in decreased breadkdown of GLP C. It inhibits SGLT-2 and cause glucosuria D. It is amylin analogue and decrease glucagon Q 15. To minimize the risk of HPA axis suppression, what is the correct method of administration of prednisolone? A. Give at night just before bedtime B. Divide in three doses and give small doses 8 hourly C. Give on alternate day D. Replace with betamethasone Answers 11. - C 12. - D 13. - B 14. - A 17. - B 18. - C 15. - C 16. - B
  • 50.
    50 Cerebellum Quick RevisionNotes Q 19. Which of the following is not used in treatment of polycystic ovarian disease? A. Letrozole B. Clomiphene citrate C. Ulipristal D. Combined oral contraceptives Q 20. Combined oral contraceptive pills act by all of the following mechanisms except? A. Inhibit implantation by bringing change in the uterus B. Inhibit ovulation C. Makes cervical mucus thick and hostile D. Increase gonadotropin secretion Answers 19. - C 20. - D 21. - A 22. - A Q 21. A 22 year old female presents 8 hours after sexual assault. It is the 13th day of her menstrual cycle. Which emergency contraceptive should be prescribed to her? A. Levonorgestrel 1.5 g single tablet B. Injection DMPA C. OCP from day 1 of next cycle D. Misoprostol Q 22. Which of the following is not used as emergency contraceptive? A. Danazol B. Levonorgestrel C. Mifepristone D. IUCD
  • 51.
    Chapter - 7Central Nervous System NEURODEGENERATIVE DISEASES These occur due to age related degeneration of neurons ALZHEIMER’S DISEASE – – It occurs due to age related degeneration of cholinergic neurons in basal nucleus of Meynert. – – Aβ-amyloid deposition is the underlying cause of neuronal degeneration. – – It is characterized by loss of memory (Dementia) DRUGS USED 1. AChE inhibitors:Q Lipid soluble drugs which have very high entry in the brain are preferred. Donepezil Rivastigmine These are DOC for Alzheimer’s dementia Gallantamine 2. NMDA receptor antagonist: – – Memantine is an NMDA receptor antagonist.Q 3. Monoclonal Antibody against Aβ-amyloid: – – Aducanumab targets the underlying cause i.e., Aβ-amyloid PARKINSONISM – – In Parkinsonism, there is deficiency of dopaminergic activity in basal ganglia of brain – – Normally, there is balance b/w dopaminergic (DA) and cholinergic (ACh) neurons – – In Parkinsonism, this balance is lost [Relative cholinergic excess] Two ways to treat Parkinsonism A. Increase dopamine B. Decrease Ach A. DOPAMINERGIC DRUGS 1. Levo-dopa Peripheral DOPA decarboxylase convert L-dopa to Dopamine. So if given alone: → Less efficacious due to less entry in brain. → DA produced outside the brain causes peripheral side effects like
  • 52.
    52 Cerebellum Quick RevisionNotes Carbidopa Benserazide ↓ ↑ Efficacy ↓ Peripheral S/E Psychosis – – Dyskinesia – – Abnormal behavior → Psychosis can occur due to excessive DA in brain – – Central S/E of levodopa cannot be prevented by carbi-dopa → Central S/E of levopa cannot be prevented by carbi-dopa 2. AmantadineQ – – Acts by releasing DA from vesicle – – Can Cause ankle edema (reversible) and Livedo reticularis (Pinkish pigmentation of skin in form of meshwork) – – Recently approved for treating Levo-dopa induced Dyskinesia as Amantadine acts as a NMDA Antagonist (Only anti Parkinsonian drug to treat dyskinesia) 3. Metabolism Inhibitors Selective MAO-B Inhibitors : Selegiline COMT Inhibitors : Entacapone 4. Dopamine Agonists → Directly works on dopamine receptors – – Pramipexole and ropinirole are DOC for Parkinsonism B. ANTI-CHOLINERGIC DRUGS → These are DOC for Drug Induced Parkinsonism Peripheral DOPA Decarboxylase inhibitors Two groups: 1. Central Anti-cholinergics: Benzhexol [Trihexyphenidyl] 2. First Generation Anti-histaminic drugs: Promethazine MULTIPLE SCLEROSIS – – Demyelinating disease Condition DOC Acute Episode Relapsing Remitting (RRMS) Primary Progressive (PPMS) Intravenous Steroids β-IFN Ocrelizumab EPILEPSYQ Seizure Special Feature First Line Drug GTCS Valproate, Lamotrigine Absence EEG shows 3 spike / wave pattern Valproate, Ethosuximide Focal Temporal lobe Carbamazepine (DOC) Oxcarbazepine Levetiracetam, (DOC in elderly) Myoclonic Valproate Atonic Valproate Lennox Gastaut Syndrome Valproate, Rufinamide Febrile seizures Diazepam Status Epilepticus Lorazepam Infantile spasms Also called Salaam seizures Seen in West syndrome ACTH (DOC), Vigabatrin Eclamptic seizures Due to high BP in pregnancy MgSO4 (DOC) • • First sign of toxicity is loss of deep tendon reflexes like patellar reflex Epilepsy in pregnancy - • • Don’t change drug if female is already controlled on any AED • • Least teratogenic are lamotrigine and levetiracetam – – Hypotension – – Arrhythmias – – Hypertension – – Vomiting
  • 53.
    53 Pharmacology Lamotrigine – – DOC forfocal seizures in elderly (along with levetiracetam) – – Side effects: • • Steven Johnson SyndromeQ • • Toxic Epidermal Necrolysis These side effects can be avoided by gradually increasing the dose. Sodium Valproate It can cause adverse effects like: – – Liver damage – – PancreatitisQ – – PCOD Phenytoin Adverse Effects H - Hirsutism, Hypertrophy of gums O - Osteomalacia T - Teratogenicity [Fetal Hydantoin syndrome] M - Megaloblastic Anemia [↓ Folate]Q A - Arrhythmia [Only in overdose] L - Lymphnode enlargement I - ↓ insulin (avoided in DM)Q K - ↓ Vitamin K A -Ataxias,vertigo[cerebellar symptoms] [only athighdose] Topiramate – – Can cause renal stone – – Other uses of Topiratmate (COMB) – – Craving of Alcohol – – Obesity – – Migraine prophylaxis – – Bipolar disorder Vigabatrin Retigabine – – Used or Focal seizures – – Does not act on GABA – – Can cause retinitis as side-effect. Other uses of AEDs Bipolar disorder CBZ, Valporate, Topiramate Migrane prophylaxis Topiramate, Valproate Neuropathic pain Gabapentin, Pregabalin, CBZ Restless leg syndrome Gabapentin (DOC) Arrhythmias Phenytoin ANTI-PSYCHOTIC DRUGS – – Psychosis occurs due to excessive dopamine in brain. – – Anti-phychotics drug can be divided into: 1. Typical Anti Psychotics [D2 Blockers] 2. Atypical Anti Psychotics [any other mechanism; mainly 5HT2 Blockers] Typical Antipsychotics 1. Strong D2 # – – Haloperidol [Highest risk of EPS] 2. Weak D2 # – – Chlorpromazine Side effects 1. Extra Pyramidal Symptoms [EPS] Extra Pyramidal Symptom Drug of choice 1. Dystonias [Earliest]Q Benzhexol 2. Akathisia [MC]Q Propanolol 3. Parkinsonism Benzhexol 4. Tardive dyskinesia [Very late to appear]Q Valbenazine 5. Malignant Neuroleptic Syndrome Dantrolene 2. Hyperprolactinemia – – Dopamine ↓ prolactin by stimulating D2 receptors. Therefore, antipsychotics can cause hyperprolactinemia due to D2 blockade. – – Hyperprolactinemia can result in galactorrhea and infertility
  • 54.
    54 Cerebellum Quick RevisionNotes Atypical Anti Psychotics Advantages 1. Lesser risk of EPS and hyperprolactinemia 2. Effective against both Positive as well as negative symptoms Side effects – Causelipodystrophysyndromecharacterized by • • ↑ Glucose • • ↑ Lipids • • Weight gain • • Insulin Resistance – Risk is highest with clozapine Clozapine → DOC for resistant Schizophrenia → Adverse effects are: – – Agranulocytosis [Dose independent]Q – – Seizures [Dose dependent] – – Myocarditis – – Sedation (Most common adverse effect) – – Sialorrhea (MC side effect)Q ACUTE MANIA – – Patient is usually aggressive and violent – – Rx of Acute Episode: Sedatives [Antipsychotics/ BZD] + Lithium – – Prophylaxis: Lithium is DOC. – – Bipolar disorder: DOC is lithiumQ Lithium Pharmacokinetics – – Half-life is 24 hours – – Narrow Therapeutic Index – – Given thrice a day Therapeutic drug monitoring Interactions Drug increasing toxicity are: – – Lisinopril – – Indomethacin – – Thlazides Toxicity (DAT) – – Diarrhea – – Agitation & Incordination – – Tinnitis Actions of LithiumQ L - Leucocytes I - Increase T - Tremors [MC] H - Hypothyroidism I - Increase U - Urine M - Avoided in Mothers [Lithium in pregnancy → Ebstein anomaly] DEPRESSION – – Earlier it was believed, decrease in Monoamines (5-HT > NA» DA) causes depression. – – Later it was linked with decrease in BDNF i.e., when ↑ Monoamines – – ↑ BDNF → ↑ Neuro Plasticity → ↓ Depression ANTI DEPRESSANTS – – Typical Anti-Depressants → Act by ↑ 5HT – – Atypical Anti-Depressants → Act by other mechanisms Typical Antidepressants These may be: 1. MAO - A Inhibitors – – Moclebemide – – Reversible inhibitors of MAO-A]Q Leukocytosis Polyuria – – For measuring plasma concentration: Sample taken at 12 hours after last dose. – – Plasma concentration of LithiumQ • • Acute mania → 0.8-1.2 mEq/L • • Prophylaxis → 0.5-0.8 mEq/L
  • 55.
    55 Pharmacology 2. Reuptake Inhibitors NonSelective Selective • • Inhibit reuptake of 5HT and NA • • Avoided in cardiac patients • • Indicated For severe depression • • Inhibit reuptake of 5HT • • Can be used in cardiac patients • • Indicated for mild to moderate depression A. Non-Selective Reuptake Inhibitors – – Inhibit the reuptake of both 5HT and NA – – Two classes: TCA and SNRI (i) TCA [Tricyclic antidepressants] – – Imipramine – – Desipramine – – Clomipramine – – Amitriptyline – – Nortriptyline → Adverse Effects: • • ACh#: Dry mouth, blurred vision, C/I in glaucoma • • α #: Postural hypotension • • H1 #: Sedation • • Seizures • • Arrhythmias • • Metabolic acidosis → Treatment of TCA poisoning: • • NaHCO3 to correct metabolic acidosis and reverse arrhythmiasQ (ii) SNRI [Serotonin Noradrenaline Reuptake Inhibitors] – – ↑ 5 HT and ↑ NA – – Lesser adverse effects than TCAs. – – DOC for severe depression → Drugs – – Venlafaxine – – Duloxetine – – Milnacipran – – Desvenlafaxine – – Levo-Milnacipran B. Selective Serotonin Reuptake Inhibitors → Drugs – – Fluoxetine – – Paroxetine – – Fluvoxamine – – Sertraline – – Citalopram – – Es-Citalopram – – Dapoxetine → For premature ejaculationQ Indication of SSRI • • SSRI are DOC for mild-moderate depression • • SSRI are DOC for all neurotic disorders like – – GAD – – OCD – – Bulimia – – Phobia – – PTSD – – Impulse control disorders Adverse Effects of SSRI – – Nausea (Most common) – – Anxiety (Due to up-regulation of 5HT2 receptors) – – CNS: Headache, bad dreams – – Sexual:Q • • Due to 5HT2 receptor stimulation • • Include ○ ○ Anorgasmia ○ ○ Delayed ejaculation (Dapoxetine used for Pre mature ejaculation) • • Discontinuation syndrome (Least with Fluoxetine)Q
  • 56.
    56 Cerebellum Quick RevisionNotes Atypical Anti-Depressants – – Less sexual side effects → Drugs – – Bupropion - Anti-Smoking drugQ – – Amineptin - ↑ Reuptake of 5-HT – – Tianeptin - ↑ Reuptake of 5-HT – – Vortioxetine – – Vilazodone – – Esketamine – – Brexanolone Esketamine – – Acts by blocking NMDA receptors of Glutamate – – Used as a Nasal spray for treatment resistant depression Brexanolone/ Allopregnanolone Approved for Post-partum depression. DRUG OF ABUSE Opioids Morphine – – Acts on µ, K, δ Receptors – – Stimulation of µ, K, δ Receptors cause – Analgesia µ Receptor FunctionsQ S - Sedation A – Analgesia C – Constipation R - Respiratory depression U - eUphoria M – Miosis Kappa receptors cause dysphoria Important Drugs: Morphine is used to treat pain but it should not be used to treat Biliary colic because morphine causes spasm of sphincter of Oddi which increases the intra biliary pressure that can result in rupture of bileduct.Q Tramadol → Two MOA – – Agonist at µ, k, δ receptors (opioid action) – – ↑ 5HT and NA in spinal cord (Non-opioid action) Naloxone cannot completely abolish the analgesic effect of tramadol and tapentadol Fentanyl – – Highly lipid soluble drugs – – Used for anesthesia – – Cause Post operative muscle rigidity. It is also known as Wooden chest syndrome ANTAGONISTS → Drugs Naloxone - Short acting, given IVQ Naltrexone - Long acting, given Orally DOC for acute Opioid poisoning → Naloxone DOC for maintenance in opioid poisoning → NaltrexoneQ
  • 57.
    57 Pharmacology A. Sedation B.Sudden death C. Weight gain D. Skin rash Q 8. Which of the following combination of seizure and its first line drug is not correct? A. Generalized seizure - Valproate B. Myoclonic - Phenytoin C. Focal – Carbamazepine D. Absence - Ethosuximide Q 9. Topiramate is used for the treatment of A. Lennox Gastaut syndrome B. Attention deficit hyperkinetic disorder C. Treatment of migraine D. Prophylaxis of heat stroke Q 10. A young boy was brought to hospital with complaints of few episodes of fast blinking and staring at something for around 20 seconds. ECG shows spike and wave pattern. Which of the following drug should be used for treatment? A. Phenytoin B. Sodium valproate C. Diazepam D. Carbamazepine Q11. ACTH is the treatment of A. Juvenile myoclonic epilepsy B. West syndrome C. Dravet syndrome D. Lennox Gastaut syndrome Q 12. Which of the following anti-epileptic drug is used in treatment of neuropathic pain ? 1. Gabapentin 2. Lamotrigine 3. Carbamazepine 4. Pregabalin A. 1 and 2 B. 2 and 3 C. 1, 2 and 3 D. 1, 3 and 4 Previous Years Questions Q 1. An elderly male developed the symptoms of dementia and was diagnosed as Alzheimer’s disease. Which neurotransmitter level is reduced in this disease? A. Dopamine B. Acetylcholine C. Adrenaline D. Serotonin Q 2. An elderly patient presented with tremors, rigidity and bradykinesia. The most likely neurotransmitter affected in the brain of this patient is? A. Dopamine B. GABA C. Adrenaline D. Serotonin Q 3. Which of the following drug is the only medication useful in preventing disability progression in a patient with primary progressive multiple sclerosis? A. Natalizumab B. Ocrelizumab C. Siponimod D. Rituximab Q 4. A patient presents with tremors, rigidity and bradykinesia. Which of the following drugs can be used for the treatment of this patient? A. Selegiline B. Donepezil C. Fluoxetine D. Haloperidol Q 5. A patient is on long term anticonvulsant therapy. There is progressive contractility of visual field. The likely anti-epileptic drug responsible for this adverse effect is A. Vigabatrin B. Ethosuximide C. Phenobarbital D. Levetiracetam Q 6. Least teratogenic antiepileptic drug in pregnancy is A. Valproate B. Phenytoin C. Carbamazepine D. Levetiracetam Q 7. A patient was started on lamotrigine 50 mg daily for treatment of epilepsy. Gradually, the dose of the drug is increased every 1-2 weeks to reach the final dose of 200 mg per day. This step up titration of lamotrigine dose is done in order to prevent or minimize the development of Answers 1. - B 2. - A 3. - B 4. - A 5. - A 6. - D 7. - D 8. - B 9. - A 10. - B 11. - B 12. - D
  • 58.
    58 Cerebellum Quick RevisionNotes Q 19. A 30 year old patient was started on lithium carbonate for bipolar disorder. The nurse will gave instructions on adverse effects of the therapy. The patient should report back if the following features are seen: A. Palpitations, chest pain, raised blood pressure B. Sedation, constipation, vomiting C. Tinnitus, severe diarrhea, ataxia D. Fever, skin rash, bradycardia Q 20. For plasma level monitoring, lithium estimation is done? A. Immediately after the dose B. 8 hours after last dose C. 12 hours after last dose D. 24 hours after last dose Q 21. A 25 year old female presented with mania. History revealed that her father is taking medications for bipolar disorder. Which of the following drug will you prescribe for this patient? A. Sodium valproate B. Lithium C. Carbamazepine D. Lamotrigine Q 22. Which of the following anti-depressant drug acts by inhibiting the reuptake of both serotonin and nor- adrenaline? A. Fluoxetine B. Venlafaxine C. Phenelzine D. Nortriptyline Q 23. A patient had a history of previous child with down syndrome, currently on lithium therapy present for antenatal checkup. Which of the following condition is the fetus at the greatest risk of? A. Ebstein’s anomaly B. Down’s syndrome C. Tetralogy of Fallot D. Neural tube defect Q 24. A 30 year old female presented to psychiatry OPD with symptoms of hypomania. She has a past history of mania and wants to conceive. Which of the following drug is most teratogenic? Q 13. A child born by normal vaginal delivery developed repeated attacks of flexion of neck over the trunk and jerks in the hands. EEG shows the presence of hypsarrhythmia. Anti-epileptic drug of choice for this patient is? A. Phenobarbitone B. Phenytoin C. ACTH D. Levetiracetam Q 14. First sign of MgSO4 toxicity is A. Loss of patellar reflex B. Respiratory distress C. Cardiac arrest D. Decrease in urine output Q 15. Which of the following adverse effect is more with oxcarbazepine as compared to carbamazepine? A. Thrombocytopenia B. Dilutional hyponatremia C. Rash D. Hepatotoxicity Q 16. A patient of psychosis was being treated with risperidone. He presented to emergency with upward fixed gaze. What will be the treatment of this patient? A. Wait and assurance B. Intramuscular Promethazine C. Injection Diazepam D. Injection Lorazepam Q 17. A patient was recently started on Fluphenazine. Few weeks later, he developed tremors, rigidity, bradykinesia and excessive salivation. First line of management for this patient is A. Selegiline B. Trihexyphenidyl C. Pramipexole D. Amantadine Q 18. A psychotropic drug inhibiting the reuptake of serotonin is likely to cause which of the following adverse effect? A. Visual disturbance B. Constipation C. Dry mouth D. Sexual dysfunction Answers 13. - C 14. - A 15. - B 16. - B 19. - C 20. - C 23. - A 24. - A 17. - B 18. - D 21. - B 22. - B
  • 59.
    59 Pharmacology Q 30. Whichofthefollowingissafeplasmaconcentration of lithium for treatment of acute attack and prophylaxis of migraine? A. 0.6-1.2 mEq/L B. 0.6-1 mEq/L C. 2-3 mEq/L D. 1-2 mEq/L Q 31. A patient suffering from depression has to be started on anti-depressant drug. Which of the following is least likely to cause sexual side effects? A. Venlafaxine B. Escitalopram C. Imipramine D. Bupropion Q 32. A 22 year old female with bipolar disorder was on lithium therapy. Which of the following statements about the therapy is not correct A. Hemodialysis is not useful in lithium overdose B. Lithium decreases thyroid function C. Lithium toxicity is increased by thiazides D. Lithium is avoided in pregnancy due to its teratogenic effects Q 33. Which of the following drug used for pain relief in arthritis acts by both opioid and non opioid mechanisms? A. Paracetamol B. Tramadol C. Ketorolac D. Diclofenac A. Valproate B. Lithium C. Carbamazepine D. Olanzapine Q 25. Which of the following is a novel antidepressant drug? A. Vilazodone B. Asenapine C. Flibanserin D. Lurasidone Q 26. Which of the following antidepressant drug should be avoided in a patient of angle closure glaucoma? A. Sertraline B. Amitriptyline C. Mirtazapine D. Venlafaxine Q27.Apatientonanti-depressanttherapypresentswith elevated body temperature, dilated pupil, palpitations and low blood pressure. ECG shows tachycardia, broad QRS complex and right axis deviation. Which of the following interventions must be done immediately? A. Wait and watch B. Intravenous sodium bicarbonate C. Intravenous esmolol D. DC cardioversion Q 28. A patient on lithium therapy developed hypertension. He was started on thiazides for hypertension. After few days, he developed coarse tremors and other symptoms suggestive of lithium toxicity. Explain the likely mechanism of this interaction. A. Thiazide inhibits the metabolism of lithium B. Thiazides act as an add on drug to lithium C. Thiazides increase the tubular reabsorption of lithium D. Thiazides cause loss of water thereby increase lithium levels. Q 29. A female patient was on lithium therapy for bipolar disorder for 6 months. She kept the fast for few days due to religious reasons and presented with seizures, coarse tremors, confusion and weakness of limbs. Which of the following should be done to diagnose her condition? A. Serum Electrolytes B.Serum lithium levels C. ECG D. MRI Answers 25. - A 26. - B 27. - B 28. - C 29. - A 30. - A 31. - D 32. - A 33. - B
  • 60.
    DRUGS AFFECTING BLOODFLOW ANTI PLATELET DRUGS Chapter - 8 Hematology 1. Aspirin Inhibit COX → ↓TXA2 2. Clopidogrel Ticlopidine Acts on ADP 3. Abciximab Tirofiban Eptifibatide Act on GP IIb/IIIaQ 4. Atopaxar Vorapaxar Act on PAR-1 receptors of thrombinQ ANTI COAGULANTS These are divided into oral and parenteral anticoagulants Oral Anti-Coagulants • • Vitamin K inhibitors • • Direct thrombin inhibitors • • Factor Xa inhibitor 1. Vitamin K inhibitors → Includes dicumarol and warfarin Properties of Warfarin: 1. Oral anticoagulant 2. Inhibit vitamin - K 3. Takes 4-5 days to produce action 4. Mainly used for maintenance purpose 5. Contraindicated in pregnancy 6. Effect of Warfarin is monitored by PT/INR Warfarin Overdose: • • Overdose of Warfarin causes bleeding • • Active Factors like IIa, VIIa, IXa, Xa (which are Known as Four Factor complex (or) Prothrombin Factor complex) is the Treatment of choice.Q • • If Four Factor complex is not available, then fresh frozen plasma can be used. • • If the fresh frozen plasma is also not available, whole blood should be given • • But the Treatment of choice for bleeding tendency due to warfarin is Vitamin K • • Vitamin K is also antidote for Warfarin overdose. 2. Direct Thrombin Inhibitors • • Dabigatran - Can be given Orally and does not require monitoringQ 3. Direct factor Xa inhibitors Drugs are • • Rivaroxaban • • Apixaban • • Edoxaban • • Betrixaban RIVAR – REVERSIBLE O – ORAL XA – XA B – BLOCKER (OR) AN – ANTAGONIST
  • 61.
    61 Pharmacology Injectable Anti-Coagulants 1. IndirectThrombin Inhibitors 2. Direct Thrombin Inhibitors 1. Indirect Thrombin Inhibitors [Heparin] UFH Activate antithrombin Inhibit factor IIa = Xa LMWH Activate antithrombin Inhibit factor Xa > llaQ Fondaparinux Activate antithrombin Only inhibits factor XaQ Heparins 1. Route → S.C. or IV 2. Activate anti-thrombin 3. Immediate Action → Useful in acute conditions 4. Anti-coagulant of choice in pregnancy 5. Monitoring done by a PTT 6. Antidote → Protamine Sulphate WARFARIN HEPARIN Route Oral S/C or IV MOA Inhibit vitamin K Activate AT – III Onset 4-5 days Immediate Use Maintenance Acute condition Pregnancy C/I DOC Monitoring PT/INR aPTTQ Antidote Vitamin K Protamine 2. Direct Thrombin Inhibitors (DTI) • • Bivalirudin, argatroban and melagatran are injectable DTI.Q • • Hirudin and lepirudin are not used now • • These are DOC for heparin induced thrombocytopenia (HIT) ANTIDOTES OF ANTI-COAGULANTS Antidote Anticoagulant Vitamin K Protamine sulfate Idarucizumab Andexanet-Alpha Warfarin HeparinQ DabigatranQ Factor Xa inhibitors e.g., Apixaban FIBRINOLYTIC DRUGS • • All drugs in this group are tissue plasminogen activators. • • tPA converts plasminogen to plasmin that breaks the thrombus • • These are used for acute MI, acute stroke and acute DVT → Drugs S – Streptokinase U – Urokinase R – Reteplase A – Alteplase T – Tenecteplase Overdose of thrombolytics → Leads to bleeding → Antidotes: – – Epsilon Amino Caproic Acid [EACA] – – Tranexamic Acid. DRUGS AFFECTING BLOOD CELLS • • Hematinics • • Growth factors HEMATINICS These are nutritional substances which help in formation of blood. e.g. 1. Iron (Fe) 2. Folic acid (FA) 3. Vitamin B12 Iron Deficiency Anemia • • Treatment of choice is Oral iron. Oral Iron • • Various preparations like ferrous sulphate, ferrous fumarate are available. – – For adults, tablets are given – – For children drops are available. These should be given deep in mouth or else they cause skin pigmentation • • Earliest response - ReticulocytosisQ • • If Hb is improving by 0.5 g/dl/week, that means adequate response
  • 62.
    62 Cerebellum Quick RevisionNotes • • Oral iron treatment is continued for 2-3 months even after the Hb levels come to normal to replenish the iron stores in body. • • Factors affecting – – Ascorbic acid : Increase Absorption – – Phytates and oxalates :Decrease Absorption Injectable Iron • • Preparations of injectable iron are: – – Iron Dextran –Can be given IV as well as IM – – Iron Sorbital citrate (Used IM only) • • Intramuscular iron is given by Z-tract technique to avoid pigmentation HEMATOPOIETIC GROWTH FACTORS Cells Growth Factor Drug Indications RBC Erythropoietin Darbopoietin Anemia due to chronic renal failure Anemia due to bone marrow suppression WBC G-CSF GM-CSF Filgrastim Sargramostim Leukopenia due to bone marrow suppression Platelets IL-11 Oprelvekin Thrombocytopenia due to bone marrow suppression Previous Years Questions Q1. Which of the following is an oral direct thrombin inhibitor? A. Dabigatran B. Rivaroxaban C. Warfarin D. Lepirudin Q2. What is the mechanism of action of tPA? A. Fibrinolysis B. Inhibition of factor V and VII C. Inhibition of factor III and V D. Activation of anti-thrombin III Q3. A female patient was taking warfarin for prosthetic heart valves. She became pregnant. What advise will you give regarding use of this drug in early pregnancy? A. Continue warfarin without any concern B. Continue warfarin but add vitamin K to the therapy C. Change warfarin to heparin D. Terminate the pregnancy Q4. In the given diagram, identify drug Z marked by the arrow A. Clopidogrel B. Heparin C. Dicumarol D. Alteplase Q5. A patient presented to hospital with chest pain. ECG of the patient confirms it to be non ST elevation myocardial infarction. Which of the following drug useful in this patient acts by inhibiting platelet aggregation? A. Clopidogrel B.Streptokinase C. Low molecular weight heparin D.Warfarin Answers 1. - A 2. - A 3. - C 4. - C 5. - A
  • 63.
    63 Pharmacology Drug A DrugB Drug C a Aspirin Vorapaxar Prasugrel b Dipyridamole Eptifibatide Vorapaxar c Aspirin Eptifibatide Prasugrel d Dipyridamole Prasugrel Eptifibatide Q10. Which of the following statements is most correct regarding mechanism of action of dicumarol? A. It acts as a calcium chelator and reduces the availability of calcium in coagulation pathway B. It binds and activates anti-thrombin 3 that accelerates its interaction with thrombin and factor Xa resulting in their degradation C. It acts as a Vitamin K inhibitor that results in inhibition of activation of clotting factors 2,7,9 and 10 D. It inhibits tissue plasminogen activator resulting in stoppage of conversion of plasminogen to plasmin Q11. Vitamin that increases the absorption of iron from stomach is? A. Vitamin A B. Vitamin B12 C. Vitamin C D. Vitamin D Q12. Excessive phytates intake in the diet may lead to deficiency of A. Proteins B. Iron C. Vitamin B12 D. Vitamin D Q13. Indication for use of Pegylated Filgrastim is in the correction of: A. Anaemia B. Neutropenia C. Thrombocytopenia D. Pancytopenia Q6. A deep vein thrombosis patient was started on an anticoagulant therapy. Next day, the patient presented with the features shown in the diagram below. Likely drug implicated for this adverse effect is A. Heparin B. Rivaroxaban C. Warfarin D. Dabigatran Q7. Among the following drugs, oral factor Xa inhibitor is: A. Dabigatran etexilate B. Rivaroxaban C. Fondaparinux D. Bivalirudin Q8. A 45 year old patient being treated with low dose aspirin since 6 months presented with rectal bleeding. Inhibition of which of the following substance is likely to responsible for the bleeding? A. TXA2 B. LT C. Bradykinin D. PGI2 Q9. Mechanism of action of some antiplatelet drugs is shown in the given diagram. Which of the following is correct match: Answers 6. - C 7. - B 8. - A 9. - C 10. - C 11. - C 12. - B 13. - B
  • 64.
    Chapter - 9Gastrointestinal Tract PEPTIC ULCER DISEASE → Due to excessive acid in stomach Treatment 1. ↓ ACID → HCl produced by Parietal cell of stomach → Proton Pump [H+ -K+ -Pump] helps in secretion of acid – – Stimulated by ƒ ƒ ACh [M1 ] ƒ ƒ Histamine [H2 ] ƒ ƒ Gastrin [CCK] – – Inhibited by PGE2 Drugs ↓ Acid M1 blockers H2 blockers PGE2 PPI Pirenzepine Telenzepine Cimetidine Ranitidine Famotidine Loxatidine Misoprostol Omeprazole Esomeprazole Pantoprazole Lansoprazole Rabeprazole Most specific drug for NSAID induced Peptic ulcer MisoprostolQ DOC for NSAID induced Peptic ulcer Proton Pump lnhibitorsQ PPls [Proton Pump Inhibitors] • • Irreversible inhibitors • • Example of Hit and Run Drugs • • Exert systemic effect [Do not work locally] • • Given with acid resistant coating (Enteric coating) Indications • DOC for PUD due to any reason • DOC for GERD • DOC for Zollinger Ellison Syndrome Adverse Effects (on long-term use) • • ↓ Ca2+ [Osteoporosis] • • ↓ Vit B12 [Megaloblastic anaemia]Q • • ↑ Infections 2. ANTACIDS → Fastest pain relievers of PUD → Include – – AI [OH]3 → Cause constipation – – Mg [OH]2 → Cause Diarrhoea → Given in combination 3. ULCER PROTECTIVE DRUGS → Sucralfate → Sucralfate acts by Polymerization, requires acidic pH [<4] – – Should not be combined with antacids → Inhibits absorption of several drugs like phenytoin. So, a gap of minimum 120 minutes should be kept between two drugs 4. ANTI-H. PYLORI DRUGS • Amoxycillin • Metronidazole • Clarithromycin Triple Drug Therapy • • Used for H. pylori associated PUD • • PPI + 2AMA used C → Clarithromycin A → Amoxycillin P → PPI Preferred triple drug therapyQ Given for 2 weeks
  • 65.
    65 Pharmacology Previous Years Questions Q1.A patient on phenytoin for seizure disorder was prescribed sucralfate 4 times a day for peptic ulcer. What should be the minimum duration between consumption of two drugs? A. 30 min B. 60 min C. 90 min D. 120 min Q2. A female with ovarian cancer was on cisplatin therapy. He presented to hospital with several episodes of vomiting. After giving an antiemetic drug, the patient developed dystonia. The anti-emetic drug most likely to be responsible for these features is A. Metoclopramide B. Meclizine C. Ondansetron D. Scopolamine Q3. Which of the following is not a prokinetic? A. 5HT4 agonist B. D2 blocker C. Macrolides D. Diphenoxymethane Q4. A patient presented to hospital with three bouts of vomiting and treated with anti-emetic drug. Vomiting subsided but after sometime, he developed abnormal movements. Which of the following drug is used for treatment of these motor symptoms? A. Benzhexol B. Cyproheptadine C. L-dopa D. Hyoscine Q5. A patient is planned to receive chemotherapy with cisplatin. Which of the following drugs are used for the treatment of chemotherapy induced nausea and vomiting A. Granisetron, aprepitant and dexamethasone B. Metoclopramide, dexamethasone and domperidone C. Prochlorperazine, granisetron and domperidone D. Promethazine, doxylamine and metoclopramide Answers 1. - D 2. - A 3. - D 4. - A ANTI-EMETIC DRUGS 1. Chemotherapy induced nausea and vomiting (CINV): Type Drug of Choice Early CINV 5HT3 antagonistsQ - Ondansetron - Granisetron - Palonosetron Delayed CINV Substance P antagonistsQ - Aprepitant - Rolapitant 2. D2 Blockers Metoclopramide DomperidoneQ Cross BBB Do not cross BBB Can cause dystonia Do not cause dystonia DOC for Levodopa induced vomiting PROKINETIC DRUGS → Used in GERD → Drugs are 1. D2 Blockers • • Domperidone • • Metoclopramide 2. 5HT4 Agonist • • Mosapride • • Prucalopride 3. Motilin Receptor Agonist • • Erythromycin 5. - A
  • 66.
    BRONCHIAL ASTHMA 1. Bronchodilators A.Sympathomimetics b2 Agonists Salmeterol → Slow acting → Only used for prophylaxis Formoterol → Fast acting → Used for acute attacks also Adverse Effects of b2 Agonists T - Tachycardia T - Tremors (Most common side effect) T - Tolerance (Mainly with long-acting beta 2 agonists) T - T wave changes (Because of hypokalaemia) These drugs can cause hyperglycaemia (but never hypoglycemia) B. Parasympatholytics M3 Blockers • • Ipratropium • • Tiotropium → Given by inhalational route C. Phosphodiesterase Inhibitors • • Include theophylline and aminophylline • • Given orally or by intravenous route (not available by inhalational route) Chapter - 10 Respiratory System Mechanism → Inhibit PDE (thereby ↑ cAMP) → Adenosine A1 receptor antagonistQ Adverse effects Due to PDE inhibition Due to ADEnosine A1 an- tagonismQ Nausea, Vomiting, Diarrhea Arrhythmias Headache Diuresis Arrhythmias Epileptic seizures → Theophylline is metabolized by microsomal enzymes, so prone to drug interactions • • Enzyme inducers (like smoking) decrease the effect, therefore smokers require higher doses • • Enzyme inhibitors (like ciprofloxacin, clarithromycin and erythromycin) can result in toxicity (seizures, arrhythmias etc.)Q 2.Drugs affecting LTs A. Steroids → DOC for prophylaxis → Also used in acute attack along with bronchodilators Function in acute attack of asthma is to ↑ the sensitivity of b2 agonists. → Preferred by inhalational route – – MC side effect is oropharyngeal candidiasis – – Topical Nystatin or clotrimazole is used to treat candidiasis – – Gargling after every dose will prevent this adverse effect
  • 67.
    67 Pharmacology Previous Years Questions Q1.A patient was taking theophylline for bronchial asthma. After starting another drug, symptoms of theophylline toxicity started appearing. Which is the likely drug started? A. Erythromycin B. Phenytoin C. Griseofulvin D. Rifampicin B. LOX inhibitors – – Zileuton C. LT Receptor antagonists – – Zafirlukast – – Montelukast 3. Mast Cell Stabilizers – – Sodium Cromoglycate – – Nedocromil → Only used for prophylaxisQ → Given by inhalational route 4. Omalizumab → Monoclonal antibody against IgEQ → Only used for prophylaxis → Given subcutaneously GINA (GLOBAL INITIATIVE FOR ASTHMA) GUIDELINES • • Drug of choice for treatment of acute attack of asthma (rescue therapy) is combination of inhalational formoterol and low dose inhaled corticosteroids.Q • • Drug of choice for maintenance therapy in asthma is also the same combination (Formoterol + Low dose ICS).Q Q2. A patient with COPD was given intravenous aminophylline therapy following which the patient developed diuresis. This is due to action on which effector? A. Adenosine receptors B. Beta 2 adrenergic receptors C. IL-10 D. Histone deacetylase Answers 1. - A 2. - A
  • 68.
    Chapter - 11Antimicrobial Agents These drugs are used to kill or inhibit the growth of micro-organisms CLASSIFICATION OF ANTIMICROBIALS Based on activity CIDAL: These kill the microoganisms These must be used to treat infections in immunocompromised person BEta lactams VAncomycin Fluroquinolones Aminoglycosides BE VA F A STATIC: These inhibit the growth of microorganisms. These cannot be relied upon if there is immunosuppression Based on Mechanism of Action Cell wall inhibitors Firmly – Fosfomycin Bind to – Beta lactans Bacterial – Bacitracin Cell – Cycloserine Vall – Vancomycin Protein inhibitors Bind at 30S ribosomes: Aminoglycosides Tetracyclines Bind to 50S ribosomes: Chloramphenicol Macrolides Clindamycin Quinpristin Linezolide Metabolism inhibitors – Sulfonamides – Trimethoprim – Pyrimethamine DNA gyrase inhibitors – Fluroquinolones – Nalidixic acid Drugs acting on membranes – Daptomycin – Polymyxin B – Polymyxin E • • Vancomycin inhibits transglycosylase and thus chain elongation step in bacterial cell wall synthesis.Q • • Beta-lactams inhibit transpeptidase and thus cross- linking of peptidoglycan chainsQ CELL WALL SYNTHESIS INHIBITORS A. BETA LACTAMS 1. Penicillins 2. Cephalosporins 3. Carbapenems 4. Monobactams 1. Penicillins Penicillin G (Benzyl Penicillin) Limitations 1. Not effective orally [Acid labile] 2. Short acting [Due to rapid tubular secretion] 3. Narrow spectrum 4. Resistance 5. Allergy
  • 69.
    69 Pharmacology 1. Acid Resistant/ Oral Penicillins V → Penicillin V (Phenoxymethyl Penicillin) O → Oxacillin D → Dicloxacillin K → Cloxacillin A → Ampicillin, Amoxycillin 2. Prolong duration of action a. Probenecid competes with Penicillin for transporters in PT → ↑ Duration of action of Penicillin b. Depot Preparations • • Benzathine Penicillin G → Longest acting Penicillin • • Procaine Penicillin G – – Depot preparations are given by IM route only 3. Spectrum of Penicillins • • Mainly against gram positive bacteria. • • Not effective against most gram negative bacilli. Extended (Wide) Spectrum PenicillinsQ A → Ampicillin, Amoxycillin Ci → Carbenicillin Ty → Ticarcillin M → Mezlocillin A → Azlocillin P → Piperacillin – – All of these are effective against Pseudomonas except ampicillin and amoxycillin 4. Solving problem of resistance A. b Lactamase Inhibitors • • β-lactams break the structure of penicillin at β-lactam ring • • Clavulanic acid, sulbactam and tazobactam inhibit these enzymes and prevent resistance • • Combinations are: – – Clavulanic Acid + Amoxycillin – – Sulbactam +Ampicillin – – Tazobactam + Piperacillin B. Penicillinase Resistant Penicillins C → Cloxacillin O → Oxacillin N → Nafcillin D → Dicloxacillin O M → Methicillin [Most resistant] MRSA [Methicillin Resistant staph. aureus] - Resistance is due to altered Penicillin Binding Proteins - All β-lactams are ineffective except 5th gen cephalosporins 5. Allergy • • Skin testing done by intradermal injection of drug • • Cross Allergy → If allergic to one penicillin, all β lactams can cause allergy except monobactam Indications of Penicillins Penicillins are First Line Drugs inQ L → Listeria (DOC is ampicillin) A → Actinomycosis S → Syphilis T → Tetanus M → Meningococcus AN → Anthrax 2. Cephalosporins 1st Gen 2nd Gen 3rd Gen 4th Gen 5th Gen Cefazolin Cefalexin Cefadroxil Cefuroxime Cefoxitin Cefaclor Cefixime Cefotaxime Ceftizoxime Cefpodoxime Ceftazidime Cefoperazone Ceftriaxone Ceftibuten Cefepime Cefpirome Ceftibiprole Ceftaroline • • Cefazolin is DOC for surgical prophylaxis • • 5th generation are effective against MRSA A. Cephalosporins secreted in bile • • Safe in renal failure • • Include – – Cefoperazone – – Ceftriaxone
  • 70.
    70 Cerebellum Quick RevisionNotes Antimicrobial Agents That are Secreted in Bile Cef in --- Cefoperazone,Q Ceftriaxone The --- Tigecycline R --- Rifampicin E --- Erythromycin N --- Nafcillin A --- Ampicillin L --- Lincosamides [Clindamycin] Disease --- Doxycycline B. Anti-Pseudomonal Cephalosporins → Include: – – Cefepime – – Cefpirome – – Cefoperazone – – Ceftazidime [Most effective anti-Pseudomonal cephalosporin]Q C. Disulfiram Like Reaction → Should not be given with alcohol → Include: • • CefoperazoneQ • • Moxalactam D. Hypoprothrombinemia (↓ Prothrombin) → ↑ Bleeding tendency → ↑ Risk of bleeding with warfarin → Avoided in hemophilia patients → Include: • • Cefoperazone • • Moxalactam 3. Carbapenems Imipenem: • • Effective against Gram (+), Gram (-) and Anaerobes • • Always given with Cilastatin because if given alone it is broken down by dehydropeptidase enzyme in the Kidney • • Imipenem is a broad spectrum antibiotic, it is also effective against Pseudomonas. Side effect : Seizures Contraindication : Epileptic patientsQ Other Carbapenems: Meropenem Ertapenem Doripenem Faropenem 4. Monobactam Only drug in the group is AztreonamQ → Do not show cross allergy → Effective only against Gm -ve bacteria including Pseudomonas B. VANCOMYCIN → It is not effective orally [Not Absorbed] Adverse Effects: • • When given by IV route → releases Histamine - Red man syndromeQ • • Nephrotoxic • • Ototoxic Indications • • DOC for MRSA infections • • Can be used for Pseudomembranous Colitis (Now DOC is fidaxomicin) • • Not effective against PseudomonasQ DOC for MRSA : Vancomycin DOC for VRSA : Daptomycin DOC for VRSA pneumonia : Linezolide PSEUDOMEMBRANOUS COLITIS • • It is a type of superinfection • • MC bacteria involved: Clostridium difficile • • MC antimicrobials implicated are: – – 3rd Gen. Cephalosporins > Clindamycin > Ampi or Amoxycillin > FQQ Treatment: DOC : Fidaxomicin (Low chances of relapse)Q Alternative : Oral vancomycin, Metronidazole Monoclonal Ab against toxin : Bezlotoxumab Cilastatin not required Lesser risk of seizures
  • 71.
    71 Pharmacology PROTEIN SYNTHESIS INHIBITORS →Drugs inhibit protein synthesis by binding to 30S or 50S → It is rememberred as buy AT - 30, SELL @ 50 – – Aminoglycosides and Tetracyclines bind at 30S ribosomes – – Rest all (streptogramins, Erythromycin group, Linizolid and Lincosamides) bind at 50S ribosomes Aminoglycosides Drugs – – Streptomycin – – Gentamicin – – Amikacin General Properties • • Not effective orally [Not absorbed] • • Active mainly on Gm -ve [Including Pseudomonas] • • Not effective on anaerobic bacteria • • Cidal drugs (Only protein synthesis inhibitors which are cidal) • • These are nephrotoxic, ototoxic and can cause neuromuscular blockade Tetracyclines - Demeclocycline - Doxycycline - Minocycline Adverse Effects K – Kidney Failure – All are C/I except Doxycycline A - Anti-anabolic P – Phototoxic I – Insipidus diabetes (Inhibit ADH release) L – Liver Failure C/I D – Dentition and Bone problems (C/I in pregnancy andchildren < 8 years)Q E – Not to be given after Expiry [Risk of FanconiSyndrome] V – Vestibular dysfunction Uses S – SIADH [Demeclocycline] R – Rickettsia [DOC] I – Granuloma lnguinale L – LGV A – Atypical pNeumonia [DOC – Macrolides] N K – Cholera [DOC] A – Luminal Amoebiasis [DOC For amoebiasis → Metronidazole] Resistance: • • Due to development of efflux pumps Streptogramins → Quinpristin + Dalfopristin → Can be used for VRSA Macrolides – – Erythromycin – – Clarithromycin – – Roxithromycin – – Azithromycin Indications DOC forQ C: Chancroid, Corynebacterium L: Legionella A: Atypical Pneumonia P: Pertussis Linezolide • • DOC for VRSA pneumoniaQ • • Now approved for TB also • • It is a static drug, so not reliable in immunocompromised patients Lincosamides (Clindamycin) • • Secreted in Bile, so safe in renal failure • • Causes Pseudo membranous colitis • • Used in anaerobic bacterial infections • • DOC for lung abcess and brain abscessQ
  • 72.
    72 Cerebellum Quick RevisionNotes ANTIMETABOLITES A. Sulfonamides/Sulfa Drugs – – Sulfadoxine – – Sulfasoxazole – – Sulfamethoxazole – – Sulfadiazine – – Dapsone Adverse Effects A – Aplastic anemia B - Bilirubin displacement → Cause Kernicterus in newbornQ C - Crystalluria R - Rash A – Acetylation S – SLE H – Hemolysis in G6PD deficiency • • Sulfonamides are structural analogs of PABA, which is essential for synthesis of folic acid. Therefore, sulfonamides are competitive inhibitors of FA synthase enzyme. • • In any infection, where pus is present, which usually contains PABA, Sulfonamides are unlikely to be effective. B. Combinations 1. Cotrimoxazole Trimethoprim (T) + Sulfamethoxazole (S) • • Ratio for best bactericidal activity → 1: 20 (T:S) • • Ratio in tablet to attain this ratio → 1: 5 (T:S) Cotrimoxazole is DOC For P → Pneumocystis jiroveci N → Nocardia B → Burkholderia cepacian 2. Sulfadoxine + Pyrimethamine • • Indicated in Parasitic infections → Malaria → Toxoplasmosis DNA GYRASE INHIBITORS • • DNA Gyrase - Introduces negative supercoils and helps in replication. • • DNA gyrase Inhibitors inhibit replication by preventing uncoiling. • • The drugs are fluoroquinolones Fluoroquinolones Drugs: • • Norfloxacin • • Ofloxacin • • Ciprofloxacin • • Levofloxacin • • Moxifloxacin General Properties • • Oral cidal drugs • • Wide spectrum [Effective against Gm + ve as well as Gm -ve] • • C/I in pregnancy and children (<18 yrs) [Cause cartilage and tendon damage]Q • • Induce seizures [Avoided in Epilepsy] • • C/I in Renal Failure ExceptionQ P – Pefloxacin M – Moxifloxacin T – Trovafloxacin Safe in renal failure Avoided in liver disease Not effective in UTI Respiratory FQQ O – Ofloxacin M – Moxifloxacin G – Gatifloxacin Levofloxacin [Isomer of Ofloxacin, Long acting] These are active against respiratory infections caused by • • Gm +ve bacteria • • Gm -ve bacteria • • Atypical bacteria • • Mycobaterium TB DRUGS NOT EFFECTIVE AGAINST PARTICULAR BACTERIA Bacteria Resistant to DOC 1. Mycoplasma Cell wall inhibitors Macrolides 2. MRSA Beta lactams Vancomycin 3. Pseudomonas Vancomycin Aminoglycoside + Ceftazidime 4. Enteric fever Aminoglycosides Ceftriaxone 5. Anaerobes Aminoglycosides Metronidazole
  • 73.
    73 Pharmacology TUBERCULOSIS FIRST LINE DRUGS H→ Isoniazid R → Rifampicin [RCIN] Z → Pyrazinamide E → Ethambutol S → Streptomycin (Not first line now) Activity Bacteria Hepatotoxic Pregnancy H Cidal Both √ Safe R Cidal Both √ Safe Z Cidal i/c √ √ √ Avoided E Static Both X Safe S Cidal e/c X C/I lsoniazid (INH) • • INH is activated by catalase peroxidase (formed by Kat G)Q enzyme of mycobacteria. It acts by inhibiting the formation of mycolic acid. • • Causes pyridoxine (Vitamin B6) deficiency resulting in peripheral neuropathy. So, pyridoxine is used for treatment as well as prevention • • Hepatotoxic (INH: lsoniazid causes Neuropathy and Hepatotoxicity)Q Rifampicin • • Act by inhibiting RNA polymerase of mycobacteria by binding to its β-subunit. It thus inhibits transcription. • • Should be given on empty stomach • • Secreted in Bile → Safe in renal failure • • Enzyme Inducer Interactions Warfarin Heparin OCP Other contraceptive method Replace with Replace with Other Uses: • • Leprosy • • Effective against Gram positive bacteria (including MRSA) • • Effective against Gram negative bacteria (including Pseudomonas) Other First Line Drugs • • Pyrazinamide causes gout • • Ethambutol causes red-green color blindness (optic neuritis) SECOND LINE DRUGS A. Cidal Drugs 1. FQ • • Ofloxacin • • Moxifloxacin • • Gatifloxacin • • Levofloxacin 2. Injectable • • Capreomycin • • Kanamycin • • Amikacin • • Streptomycin B. Drugs used for other conditions, now approved for TB 1. Linezolide – Also used for VRSA 2. Clofazimine – Also used for multibacillary leprosy C. Other static drugs: 1. Cycloserine – Causes neuropsychiatric adverse effects 2. Ethionamide – Hepatotoxic 3. PAS – Causes hypothyroidism 4. Thioacetazone – Never given in HIV patients D. New drugs: 1. Bedaquiline 2. Delamanid 3. Pretomanid TREATMENT OF TUBERCULOSIS (NTEP) Drug Sensitive TB: 2HRZE + 4 HRE
  • 74.
    74 Cerebellum Quick RevisionNotes Drug Resistant TB Multi drug (MDR) Resistant to H+R Rifampicin resistance Resistant to R but sensitive to H Pre-XDR Resistant to H + R + FQ Extensive (XDR) Resistant to H + R + FQ + One of Bedaquiline or Linezolide For TB with HIV – – First start treatment of TB (ATT) – – After 2 weeks, start treatment of HIV (ART) LEPROSY Rifampicin 600 mg Once monthly Supervised Clofazimine 300 mg Once monthly Supervised Clofazimine 50 mg Once daily for 28 days Unsupervised Dapsone 100 mg Once daily for 28 days Unsupervised Above regimen is given for – 12 months in multi-bacillary leprosy – 6 months in pauci-bacillary leprosy Lepra Reactions – – DOC for both type 1 and type 2 Lepra reaction is steroids – – MDT for leprosy should continueQ ANTI-HIV DRUGS 1. Fusion Inhibitors Enfuvirtide Maraviroc • Binds with GP 41 of Envelope and Fusion of Virus with T cell is Inhibited • Given subcutaneously • Binds with CCR-5 • Given orally 2. Reverse Transcriptase Inhibitors(RTI) → Inhibit reverse transcriptase (RNA dependent DNA polymerase) → May be competitive (NRTI) or Non-competitive (NNRTI) A. Competitive RTI NRTI (Nucleotide or side RT inhibitors) Nucleoside RTI Nucleotide RTI Zidovudine Lamivudine Stavudine Didanosine Zalcitabine Emtricitabine Abacavir Tenofovir
  • 75.
    75 Pharmacology NRTI Adverse Effect Zidovudine Abacavir Zalcitabine Emtricitabine Didanosine Stavudine BoneMarrow SuppressionQ MI Aphthous ulcers in mouth Pigmentation of palms and soles Maximum risk of pancreatitis Maximum risk of peripheral neuropa- thy B. Non-Competitive RTI (NNRTI) – – Efavirenz – – Nevirapine – – Delavirdine 3. Integrase Inhibitors → Can be given orally → One of the first line drugs for HIV now.Q → Drugs include – – Raltegravir – – Elvitegravir – – Dolutegravir 4. Protease Inhibitors • • Ritonavir • • Lopinavir • • Amprenavir • • Fosamprenavir • • Atazanavir • • Saquinavir • • Nelfinavir • • lndinavir Properties of Protease Inhibitors • • Substrates of CYP3A4 • • Inhibitors of CYP 3A4 – – Strongest is ritonavirQ – – Boosts the effect of other protease inhibitors • • Cause lipodystrophy syndrome – – ↑ Glucose – – ↑ Lipids – – Insulin resistance – – Weight gain CLINICAL MANAGEMENT OF HIV 1. Treatment of HIV • • Called HAART (Highly Active Anti Retro Viral Therapy) • • Should be given to All HIV positive patients irrespective of CD4 count • • Given for life long duration • • Minimum 3 drugs (from minimum 2 groups) should be used • • First line therapy is – – 2 NRTI +1 NNRT/ integrase Inhibitors – – Commonly used – T + L + E or T + L + DQ [T – Tenofovir, L – Lamivudine, E – Efavirenz, D – Dolutegravir] 2. Post exposure prophylaxis → To prevent development of HIV after exposure → Used commonly in health care workers → Should be started as early as possible after exposure (within maximum limit of 72 hours) → Should be given for 28 days (4 weeks)Q → All the drugs are given orally → Drugs: Tenofovir +Lamivudine + ProteaseQ Inhibitors (or integrase inhibitors) ANTI-INFLUENZA DRUGS Uncoating Inhibitors Neuraminidase inhibitors Amantadine Rimantadine Inhibit release of virus from cell • • Oseltamivir - Oral • • Zanamivir - Inhalation • • Peramivir - Parenteral D.O.C for Bird flu (H5N1) and Swine flu (H1N1) ANTI-HERPES VIRUS DRUGS • • HSV-1 • • Mucocutaneous Herpes and Herpes Encephalitis • • HSV-2 • • Genital Herpes • • VZV • • Chicken pox • • DOC for all of them is ACYCLOVIR • • Ganciclovir is DOC for CMV.
  • 76.
    76 Cerebellum Quick RevisionNotes ANTI-HEPATITIS VIRUS DRUGS Hepatitis B L : Lamivudine E : Emtricitabine T : Tenofovir (DOC) Hepatitis C → Previously treated with interferon and ribavirin → Treatment was very toxic → Now all oral treatment is used New Oral Drugs for Hepatitis C Protease Inhibitors NS 5A Inhibitors NS 5B Inhibitors Previrs Asvirs Buvirs Telaprevir Elbasvir Sofosbuvir Simprevir Ledipasvir Dasabuvir Boceprevir Daclatasvir Beclabuvir Grazoprevir Ombitasvir Paritaprevir Pimbrentasvir DRUGS FOR COVID-19 • • Caused by Novel corona virus • • Most cases are self-limiting Important drugs 1. Steroids • • Only life saving drugs in COVID-19 pneumonia. • • Safe in children • • Increase the risk of infections like mucormycosis 2. Remdesivir • • Inhibit RNA dependent RNA polymerase.Q • • Given intravenously. • • Effective in first 10 days of illness only. • • Given with steroids (or baricitinib). • • Only US-FDA approved drug for COVID-19 pneumonia. 3. Monoclonal antibodies against spike protein • • Drugs include Bebtelovimab • • Indicated for OPD treatment • • Decrease risk of hospitalization. ANTIFUNGAL DRUGS 1. TOPICAL ANTIFUNGAL DRUGS: → Used for dermatopytosis e.g. azoles → Used for steroid induced oropharyngeal candidiasis e.g. nystatin, clotrimazole Drugs: C : Ciclipirox olamine A : Azoles, Amorolofine T : Terbinafine Sertaconazole (Has anti-inflammatory and anti-pruritic activity) 2. SYSTEMIC ANTIFUGAL DRUGS DRUG MECHANISM USE Azoles Inhibit lanosterol 14-a- demethylase DOC for Candidasis is fluconazole DOC for Aspergillosis is voriconazoleQ Amphotericin -B Bind to ergosterol and create pores Mucormycosis (DOC) Cryptococcal meningitis (DOC) Kala azar (DOC) Terbinafine Inhibit squalene epoxidase Dermatophytosis (DOC) Griseofulvin Inhibit mitotic spindle Dermatophytosis 5-Flucytosine Inhibit DNA Polymerase With AMB for cryptococcal meningitis Caspofungin Cell wall inhibitorQ Candidasis Aspergillosis Note: AMB is nephrotoxic but Liposomal AMB is less nephrotoxic
  • 77.
    77 Pharmacology ANTI-PARASITIC DRUGS MALARIA • • Causedby Plamodium • • Transmitted by female Anopheles Treatment of Malaria Type of Malaria DOC DOC in 1st Trimester P. vivax malaria Chloroquine Chloroquine P falciparum malaria ACT Quinine Complicated or severe or cerebral Malaria IV Artesunate IV Artesunate Artemisinin Combination Therapy [ACT] • • Artemisinin + Long acting drug • • DOC for chloroquine resistant malaria • • Given orally • • Lumefantrine + Artemether: DOC in North Eastern States • • Artesunate + Sulfadoxine - Pyrimethamine: DOC for rest of India Radical Cure • • For P.vivax Malaria • • DOC is primaquine • • Given for 14 days • • C/I in G-6-PD deficiency, pregnancy and infants • • Tafenoquine is single dose radial cure of P.vivax malaria AMOEBIASIS Drug of Choice Luminal amoebiasis (Carrier state) Diloxanide Furoate (or Paromomycin)Q Intestinal and Hepatic amoebiasis Nitroimidazole (Nidazole) e.g. Metronidazole, Tinidazole, Secnidazole, Ornidazole, Satranidazole *Nidazoles can cause disulfiram like reaction, so are C/I in alcoholics USES OF METRONIDAZOLE:Q G - Giardiasis, Gardnerella vaginalis (bacterial vaginosis) U - Ulcer (Peptic ulcer) P - Pseudomembranous colitis T - Trichomoniasis A - Amoebiasis, Anaerobic bacterial infections
  • 78.
    78 Cerebellum Quick RevisionNotes Answers 1. - D 2. - A 3. - A 4. - A 5. - C Previous Years Questions Q1. The given diagram shows the steps in formation of bacterial cell wall. Identify the site of action of beta lactam antimicrobials: Q2. Which of the following cephalosporins can increase the effect of warfarin resulting in raised INR and increased risk of bleeding? A. Cefoperazone B. Cefixime C. Ceftibiprole D. Ceftazidime Q3. Carbapenem with maximum seizure risk is: A. Imipenem B. Meropenem C. Ertapenem D. Doripenem Q4. Cilastatin is given in combination with Imipenem because: A. Cilastatin prevents degradation of Imipenem in kidney B. Cilastatin increases absorption of Imipenem C. Inhibits the enzymes that digest Imipenem in stomach D. Reduces side effects of Imipenem. Q5. Mechanism of resistance to penicillins via beta lactamase is A. Altered penicillin binding proteins B. Drug efflux C. Breaks drug structure D. Alteration in 50S ribosome structure
  • 79.
    79 Pharmacology Answers 6. - C 7.- C 8. - A 9. - B 10. - C 11. - A 12. - B 13. - B 14. - B 15. - A 16. - A 17. - B Q6. A patient presented with hospital acquired pneumonia. On testing he was found to be allergic to penicillin G. Which of the following drug is likely to be safe in this patient? A. Ceftriaxone B. Ampicillin C. Aztreonam D. Imipenem Q7. Mechanism of action of doxycycline is A. DNA gyrase inhibitor B. Cell wall synthesis inhibitor C. Protein synthesis inhibitor D. DNA dependent RNA polymerase inhibitor Q8. Drug of choice for Legionnaire’s disease is: A. Azithromycin B. Tigecycline C. Streptomycin D. Amoxycillin Q9. Which of the following antimicrobials is contraindicated in a patient with seizure disorder? A. Ampicillin B. Ofloxacin C. Doxycycline D. Cefixime Q10. A pregnant female with urinary tract infection took antimicrobials for the same. The baby of this female developed tendon rupture and arthropathy. What is the likely mechanism of action of the antimicrobial consumed by the pregnant female? A. Folic acid synthesis inhibitor B. Mycolic acid synthesis inhibitor C. DNA gyrase inhibitor D. DNA inhibitor Q11. Drug of choice for prophylaxis against Diphtheria is A. Erythromycin B. Rifampicin C. Cloxacillin D. Ciprofloxacin Q12. Fluoroquinolone contraindicated in liver disease is A. Levofloxain B. Pefloxacin C. Ofloxacin D. Lomefloxacin Q13. Which of the following is a second line anti- tubercular drug? A. Rifampicin B. Ethionamide C. Vancomycin D. Acyclovir Q14. All of the following are bactericidal drugs against Mycobacterium except A. Kanamycin B. Thioacetazone C. Rifapentine D. Isoniazid Q15. Which of the following drug will you omit from the prescription of a patient with XDR tuberculosis in pregnancy? A. Kanamycin B. Ethambutol C. Moxifloxacin D. Amoxycillin-clavulanic acid Q16. From the given diagram, identify the mechanism of action of isoniazid. A. Drug A B. Drug B C. Drug C D. Drug D Q17. A 48 year old patient presented to OPD with tingling and numbness of fingers. The patient is chronic alcoholic and was recently started on antitubercular treatment. What should be the treatment of this patient? A. Vitamin B3 B. Vitamin B6 C. Vitamin B1 D. Vitamin B12
  • 80.
    80 Cerebellum Quick RevisionNotes Answers 18. - B 19. - A 20. - C 21. - D 22. - C 23. - A 24. - B 25. - A 26. - A 27. - C Q18. In MDR tuberculosis, which of following drug combinations show resistance? A. Rifampicin and Fluoroquinolones B. Isoniazid and rifampicin C. Isoniazid and Pyrazinamide D. Rifampicin and kanamycin Q19. Which of the following drug acts by inhibiting the transcription of DNA to RNA? A. Rifampicin B. Nitrofurantoin C. Ciprofloxacin D. Novobiocin Q20. A female taking oral contraceptives acquired tuberculosis. After prescribing anti-tubercular therapy, physician advised the patient for alternative contraception. What is the probable reason of this advise? A. Rifampicin causes teratogenicity B. Isoniazid is teratogenic C. Rifampicinincreasesthemetabolismoforalcontraceptives D. Oral contraceptives decrease the efficacy of ATT Q21. A patient of borderline leprosy received multi drug therapy. He developed skin lesions as shown in the figure below. How should this patient be managed? A. Stop MDT and give thalidomide B. Continue MDT and give thalidomide C. Stop MDT and give steroids D. Continue MDT and give steroids Q22. A patient developed COVID-19 pneumonia and was treated. Few months later, patient presented with nasal congestion and swelling of face. There were black lesions on the nose bridge. A diagnosis of mucormycosis was made. What is the drug of choice for this condition? A. Fluconazole B. Dexamethasone C. Amphotericin B D. Azithromycin Q23. Mechanism of action of Triazoles anti-fungal drugs is: A. Inhibits ergosterol biosynthesis B. Inhibits tubulin C. Inhibits glucan synthesis D. Inhibits cell wall synthesis Q24. Drug of choice for invasive aspergillosis is A. Posaconazole B. Voriconazole C. Liposomal AMB D. Caspofungin Q25. An HIV patient presents with seizures and neck rigidity. The CSF examination shows the presence of organisms on India ink and a diagnosis of cryptococcal meningitis is made. Which of the following anti-fungal drug is used for initial treatment of this meningitis? A. Liposomal amphotericin B B. High dose fluconazole C. Fluconazole + 5 Flucytosine D. Voriconazole Q26. Which of the following drugs can be used for the treatment of severe covid-19 pneumonia in children? A. Steroids B. Remdesivir C. Ivermectin D. All of these Q27. A newly diagnosed tuberculosis patients was found to be HIV positive. Which of the following statement is true about treatment of this patient? A. Start ATT and ART together B. ARTshouldbestartedonlyifCD4countislessthan50/mcL C. ATTshouldbestartedfirstfollowedbyART2weekslater D. ARTshouldbestartedfirstfollowedbyATT2weekslater
  • 81.
    81 Pharmacology Answers 28. - A 29.- A 30. - D 31. - A 32. - A 33 - B 34. - B 35. - A 36. - B 37. - A 38. - A Q28. Which of the following drugs improves bioavailability and prolongs duration of action of Saquinavir? A. Ritonavir B. Cimetidine C. Vitamin C D. Remdesivir Q29. Mechanism of action of Remdesivir is inhibition of? A. RNA dependent RNA polymerase B. DNA dependent RNA polymerase C. Viral protease enzyme D. Cell wall synthesis Q30. Mechanism of action of Oseltamivir is A. DNA polymerase inhibition B. Inhibition of viral mRNA C. Blocking viral uncoating D. Neuraminidase inhibition Q31. Which of the following drug is associated with causation of pigmentation of hand and soles on chronic use? A. Emtricitabine B. Nevirapine C. Zidovudine D. Abacavir Q32. A lady has taken medication of ameiobiasis infection . In a party she drank alcohol. She has nausea vomiting and dizziness . Which anti-amoebic drug could have lead to interaction with alcohol to produce these symptoms? A. Metronidazole B. Nitazoxanide C. Paromomycin D. Diloxanide Q33. A female patient presented with greenish vaginal discharge. Clue cells were present and Whiff test was positive in vaginal discharge. What is the drug of choice for this condition? A. Doxycycline B. Metronidazole C. Ceftriaxone D. Fluconazole Q34. A 30 year old man travelled to Assam. After coming back he developed fever, chills and rigors and altered sensorium. The peripheral smear demonstrated the presence of P. falciparum. What is the treatment of choice for this patient? A. Chloroquine, Sulfadoxine pyrimethamine B. Intravenous Artesunate C. Quinine D. Primaquine Q35. A 25 year old male has frequent visits to rural areas and need to eat outside food. During one such visit, he developed loose stools. Which of the following drug should be used to manage this case? A. Metronidazole B. Diphenoxylate C. Loperamide D. Octreotide Q36. A female patient presented with greenish vaginal discharge and pruritus. On colposcopy, strawberry cervix is noted. What is the drug of choice for this condition? A. Ceftriaxone B. Metronidazole C. Acyclovir D. Fluconazole Q37. The drug kit shown in the diagram below is used for the treatment of A. Malaria B. Kala azar C. HIV D. Syphilis Q38. Which of the following drug has highest risk of causing hemolysis in a patient with deficiency of Glucose-6-Phosphate Dehydrogenase enzyme? A. Primaquine B. Chloroquine C. Azithromycin D. Pyrimethamine
  • 82.
    Anticancer drugs canbe divided into a. Cytotoxic b. Targeted CYTOTOXIC DRUGS Common Adverse Effects • • BM Suppression • • Alopecia • • Mucositis → Diarrhea • • Hyperuricemia • • Nausea and vomiting (CINV) 1. Alkylating Agents Drugs: If – lfosfamide Bus – Busulfan Not – Nitrosoureas • Carmustine (BCNU) • Lomustine (CCNU) • Semustine (Methyl CCNU) Present – Procarbazine Take – Temozolomide My – Melphalan, Mitomycin C Cycle – Cyclophosphamide Important Points Regarding Alkylating Agents Cyclophosphamide Cause Hemorrhagic cystitisQ Cause Pulmonary fibrosis Ifosfamide Cause Hemorrhagic cystitis Busulfan Cause pulmonary fibrosis Nitrosoureas Cause Delayed neutropenia Procarbazine Cause disulfiram-like reaction Temozolomide DOC for gliomas Melphalan Used for multiple myeloma Mitomycin-C Used topically for *Subglottic stenosisQ *Superficial bladder cancer Chapter - 12 Anti-Cancer Drugs Hemorrhagic cystitis • • Caused by cyclophosphamide and ifosmide. • • Metabolite responsible is acrolein • • Prevented by mesnaQ • • Treatment is steroids. CYCLOphosphamide : CARmustine : BUSulphan : MethoTRUCKsate : (Methotrexate) AmioDaRONE : BLEOmycin : Drugs Causing Pulmonary FibrosisQ 2. Antimetabolites • • These are S Phase Specific a. Drugs affecting Folic Acid Metabolism • • Example: Methotrexate • • Act by inhibiting dihydrofolate reductase enzyme. Uses of Methotrexate: • • Choriocarcinoma - D.O.C • • Rheumatoid arthritis - D.O.C – – Methotrexate toxicity treatment- Folinic acid (Leucovorin or Citrovorum) b. Drugs Affecting Purine Metabolism 6-Mercaptopurine Hepatotoxic 6 - Thioguanine Hepatotoxic Cladribine DOC for Hairy cell LeukamiaQ Fludarabine DOC for CLLQ
  • 83.
    83 Pharmacology c. Drugs AffectingPyrimidine Metabolism 5-Fluorouracil [5-FU] Cause Hand and foot syndrome Capecitabine Proding Gemcitabine DOC for Pancreatic carcinoma Cytarabine Cause cerebellar side effects 3. Drugs Acting on Mitotic Spindle → Specific for M-Phase of cell cycle Formation inhibitors Breakdown inhibitors Vincristine Vinblastine PaclitaxelQ S/E → Peripheral neuropathy SIADH Vincristine → Marrow sparing anticancer drug 4. Topoisomerase Inhibitors Topoisomerase I inhibitors Topoisomerase II inhibitors Irinotecan → Used for colorectal carcinoma → Cholinergic Side effects Etoposide Anthracyclines • • Doxorubicin • • Donorubicin • • Epirubicin Anthracyclines – Cause Cardiotoxicity 5. Miscellaneous Drugs a. Bleomycin • • Marrow sparing • • Cause pulmonary fibrosis • • Causes Flagellated pigmentation of skinQ b. L-Asparaginase • • Marrow sparing • • Used for ALL • • Cause Allergy • • Cause Acute PancreatitisQ TARGETED ANTICANCER DRUGS A. SMALL MOLECULES 1. Tyrosine Kinase Inhibitors DOC for Chronic Myeloid Leukemia – Imatinib General Properties 1. All end with ‘nib’ 2. Orally effective Important Tyrosine Kinase Inhibitors For CMLQ I - Imatinib [DOC] N - Nilotinib D - Dasatinib • • Imatinib is DOC for CML and GIST • • Sorafenib is DOC for hepatocellular carcinoma • • Lapatinib is used for breast cancerQ
  • 84.
    84 Cerebellum Quick RevisionNotes B. MONOCLONAL ANTIBODIES → End with ‘MAB’ → Injectable Anticancer Drugs EGFR ANTAGONISTS: • • Cetuximab: Colorectal carcinoma • • Panitumumab: Colorectal carcinoma MAB AGAINST HER – 2 • • Trastuzumab • • Pertuzumab MAB AGAINST CD20 • • Rituximab : For Non-Hodgkin Lymphoma and CLL • Used for breast cancer • Cardiotoxic IMMUNE CHECK POINT INHIBITORS • • Normally, T-cells are not activated against normal cells because an interaction between PD-1 (receptor present on T-cells) and PDL-1 (Ligand present on normal cells) inhibit T-cells. This is called immune check point. Tumor cells do not express PDL-1 and thus can be killed by T-cells. • • Some tumor cells start expressing PDL-1 on their surface and thus can evade immunity by inhibiting T-cells. • • Immune check point inhibitors are monoclonal antibodies against PD-1 or PDL-1 to stop this interaction. T-cells now can kill cancer cells. • • These drugs can result in auto-immune conditions like autoimmune hepatitis as adverse effects. Drugs: Mnemonic DrugQ Use New Drugs Act At Immune Check Point Nivolumab Durvalumab Avelumab Atezolizumab Ipilimumab Cemiplimab Pembrolizumab HL, NSCLC Multiple cancers including endometrial cancer IMMUNOSUPPRESSANTS 1. STEROIDS 2. DRUGS TARGETING THE CALCINEURIN PATHWAY a. Cyclosprine and Tacrolimus b. Daclizumab and Basiliximab c. Sirolimus a. Cyclosporine and TacrolimusQ • • Inhibit formation of IL-2 b. Sirolimus and Everolimus • • Inhibit action of IL - 2 3. BIOLOGICAL AGENTS Formed by recombinant DNA technology TNF-α inhibitors A – Adalimumab C – Certolizumab E – Etanercept INhibitor – INfliximab GOLI – GOLImumab
  • 85.
    85 Pharmacology Previous Years Questions Q1.Drug of choice for treatment of hairy cell leukemia is? A. Interferon alpha B. Fludarabine C. Pentostatin D. Cladribine Q2. Which of the following drug can cause the side- effect given in the picture? A. Bleomycin B. Mitomycin C C. Doxorubicin D. Actinomycin D Q3. A 50 year old female presented to oncologist with breast lump. On examination and investigations, breast cancer was diagnosed. Echocardiography of the patient shows ejection fraction of 25 %. Which of the following drug will you avoid in this patient? A. Epirubicin B. Irinotecan C. Cyclophosphamide D. Methotrexate Q4. A 20 year old boy presented with slow growing mass on the medial side of thigh. Investigations revealed it to be osteosarcoma and patient was started on methotrexate. Mechanism of action of methotrexate as an anticancer drug is A. Inhibition of Dihydrofolate reductase B. Inhibition of N5 tetrahydro folate reductase C. Inhibition of tyrosine kinase D. Inhibition of purine metabolism Q5. Topical application of 400 mcg/ml mitomycin C is used for A. Subglottic stenosis B. Tympanoplasty C. Rhinocerebral mucormycosis D. Nasopharyngeal bleeding Q6. Which of the following is not an immune check point inhibitor? A. Cetuximab B. Pembrolizumab C. Atezolizumab D. Nivolumab Q7. Which of the following is true about Rituximab A. Anti- CD 20, monoclonal antibody B. Anti-CD 50, monoclonal antibody C. Anti-CD 20 polyclonal antibody D. Anti-CD 50 polyclonal antibody Q8. What is mechanism of action of Cyclosporine? A. Calcineurin inhibitor B. mTOR inhibitor C. IL-2 receptor antagonist D. TNF-α inhibitor Answers 1. - D 2. - A 3. - A 4. - A 5. - A 6. - A 7. - A 8. - A
  • 86.
    LOCAL ANAESTHETIC AGENTS Drugs EsterAmide Cocaine Lignocaine Procaine Bupivacaine Chlorprocaine Prilocaine Tetracaine Etidocaine Benzocaine Ropivacaine Dibucaine Special points: • • Only LA causing vasoconstriction CocaineQ • • MC used LA Lignocaine • • Shortest acting LA Chlorpropane • • LA causing methemoglobinemia PrilocaineQ • • Maximum Cardiotoxic BupivacaineQ Local Anaesthetic Systemic Toxicity (LAST): → Characterized by – – Arrhythmias – – Cardiovascular collapse – – Seizures → Treatment is – – Cardiopulmonary resuscitation – – 20% intralipid (DOC)Q SKELETAL MUSCLE RELAXANTS NEUROMUSCULAR BLOCKERS: These may be depolarizing or non-depolarizing skeletal muscle relaxants Depolarizing Muscle Relaxants (DMR) Non Depolarizing Muscle Relaxants (NDMR) • • Act by blocking NM receptors competitively • • Example is d-Tubocurarine (Curare) • • It does not cause post opeartive muscle pain • • Release Histamine that causes bronchoconstriction and hypotensionQ Other NDMR Curium [Release less histamine] Curonium [No histamine released] Atracurium Cis-Atracurium Mivacurium [Shortest acting] Pancuronium Pipecuronium Vecuronium Rocuronium Rapacuronium • • Cis-atracurium release less histamine than atracurismQ Hoffman’s Elimination • • Shown by Atracurium and Cis-atracurium • • Muscle relaxant of choice in liver and renal diseaseQ Reversal Agents Used to reverse action of NDMR after surgery → Neostigmine: Can cause cholinergic adverse effects → Suggamadex: No cholinergic side effectsQ GENERAL ANAESTHETICS INDUCING AGENTS (INTRAVENOUS) • • Thiopentone • • Ketamine • • Propofol • • Etomidate Thiopentone • • Highly lipid soluble • • Very short acting d/t Redistribution Chapter - 13 Anaesthesia • • Acts by stimulating NM receptors • • Example is Succinylcholine (SCh)Q Succinylcholine (SCh) • • Shortest acting MR [< 5 min] • • C/I in nerve and muscle injuries [Can cause severe hyperkalemia] • • Hyperthermia [precipitate malignant hyperthermia] • • Fasciculations: Responsible for post operative muscle pain
  • 87.
    87 Pharmacology Propofol • • Painful • • DOCfor day care SurgeryQ • • Avoided in patients with egg allergy Etomidate • • Agent of choice for CVS surgery • • Causes Adrenal SuppressionQ Ketamine K → Agent of choice in kids E → Emergence Rxn (post operative delirium and hallucinations) T → Thalamo- Cortical junction (site of action) Dissociative AnesthesiaQ A → Analgesic M → Meals (can be given in full stomach) I → ↑ BP/IOP/ ICP (Agent of choice in shock) N → NMDA Blocker E → Excellent bronchodilatorQ INHALATIONAL AGENTS N2O Highest MAC (104%)Q Halothane Causes hepatitis Causes malignant hyperthermia Enflurane Seizures (Maximum risk) Isoflurane DOC for cardiovascular and neurosurgery Sevoflurane DOC for children Methoxyflurane NephrotoxicQ Desflurane Maximum irritation to respiratory pathway Xenon Ideal anaesthetic agent 1. MAC (Minimum Alveolar concentration) • • Minimum Concentration required in alveoli to produce anaesthesia Mac a 1 Potency MAC Potency Drug Maximum Minimum Least Most N2O (104%) Methoxyflurane 2. Blood Solubility Measured by blood gas partition coefficient (BGPC)Q BPGC a 1 speed of onset BGPC Onset Drug Highest Slowest Methoxyflurane Lowest Fastest Xenon COLORS OF CYLINDERS N2 O Blue (NEELA) Cyclopropane Orange (SANTRI) O2 Black and white (Black body and White shoulder) Entonox – – Blue and White (Blue body and White shoulder) – – Mixture of 50% N2 O and 50% O2 is Entonox
  • 88.
    88 Cerebellum Quick RevisionNotes Previous Years Questions Q1. Mechanism of action of curare like drugs is A. Competitive, Non depolarizing block at the Nm cholinergic receptors B. Non-competitive, Non depolarizing block at the Nm cholinergic receptors C. Competitive, Depolarizing block at the Nm cholin- ergic receptors D. Non-competitive, Depolarizing block at the Nm cholinergic receptors Q2. Reason for preferring cis-Atracurium over Atracurium is: A. Equal potency like Atracurium B. Lesser provocation of histamine release C. Short fast action D. Does not undergo Hoffman elimination Q3. A person was given a muscle relaxant that competitively blocks nicotinic receptors. Which of the following drug is used for reversal of muscle relaxation after surgery? A. Neostigmine B. Carbachol C. Succinylcholine D. Physostigmine Q4. An anesthetist injected bupivacaine in a patient for axillary nerve block. Later, the patient developed restlessness, agitation and cardiovascular collapse. Next best step in the management would be? A. Cardiac resuscitation + dopamine B. Cardiac resuscitation + dantrolene C. Cardiac resuscitation + sodium bicarbonate D. Cardiac resuscitation + 20 % intralipid Q5. A patient was admitted for surgery and halothane is being planned to be used as an anaesthetic agent. The patient was explained about the adverse effect of malignant hyperthermia with this drug. Which of the following drugs may also result in malignant hyperthermia? A. Succinylcholine B. D-Tubocurarine C. Dantrolene D. Baclofen Q6. Which of the following drug is associated with post operative delirium and hallucinations? A. Ketamine B. Thiopentone C. Fentanyl D. Halothane Q7. Inhalational anesthetic agent with highest respiratory irritation is: A. Desflurane B. Nitrous Oxide C. Sevoflurane D. Halothane Q8. Which IV anesthetic does not cause cardiac depression? A. Etomidate B. Propofol C. Methohexitone D. Thiopentone Q9. Inhalational anaesthetic agent of choice in children is A. Isoflurane B. Desflurane C. Sevoflurane D. Halothane Q10. A patient of COVID-19 requires oxygen therapy. Which of the following cylinders should be used to provide oxygen to this patient? A B C D Answers 1. - A 2. - B 3. - A 4. - D 5. - A 6. - A 7. - A 8. - A 9. - C 10. - A
  • 89.
    ANTI-SMOKING DRUGS 1. NicotineReplacement Therapy (NRT) • • Most commonly used anti-smoking drugs • • Available as chewing gums and lozenges • • Lozenges have more bioavailabilty than gums • • Do not take tea or coffee for 15 minutes after taking NRT 2. BupropionQ • • Bupropion is anti-smoking whereas buspirone is anti-anxiety 3. VarenicilineQ • • Most effective anti-smoking drug • • Can cause CVS and CNS adverse effects ANTI-OBESITY DRUGS O – Orlistat B – Bupropion + Naltrexone E – Exenatide S – Semaglutide I – LIraglutide Ty – Tirzepatide Topiramate + Phentermine • • Orlistat is oral lipase inhibitor. It inhibits absorption of fats. Major adverse effect is steatorrhea.Q • • GLP-1 analogues include exenatide, liraglutide and semaglutide • • Tirzepatide is dual GLP-1 and GIP agonist. ANTIDOTES Poisoning Antidote Beta blocker GlucagonQ Organophosphate Atropine Opioid NaloxoneQ Methanol FomepizoleQ Ethylene glycol Fomepizole Warfarin Vitamin K Chapter - 14 Miscellaneous Topics Heparin Protamine sulfate Paracetamol N. AcetylcysteineQ Atropine Physostigmine Iron Desferrioxamine Benzodiazepine FlumazenilQ Zolpidem Flumazenil Cyanide Hydroxocobalamin (or Amyl nitrite)Q Valproate hepatotoxicity L-carnitine MANAGEMENT OF HYPERKALEMIA Acute hyperkalemiaQ 1. Drugs increasing intracellular movement of K+ • • Glucose - Insulin (DOC) • • Beta 2 agonists e.g. salbutamol, epinephrine 2. Drugs reversing ECG changes • • Calcium gluconate Chronic Hyperkalemia • • Long - term oral treatment • • Drugs used: – – Patiromer ERECTILE DYSFUNCTION • • DOC: PDE-5 inhibitor – – Sildenafil – – Tadalafil (Longest acting)
  • 90.
    90 Cerebellum Quick RevisionNotes CHELATING AGENTS • • Used for heavy metal poisoning 1. BAL (British Anti Lewisite)/ Dimercaprol Indications: B - Bismuth poisoning A - Arsenic poisoning L - Lead poisoning Contra-Indications Cadmium poisoning Fe poisoning 2. Ca Na2 EDTA Indications M – Manganese poisoning I – Iron poisoning L – Lead poisoning K – Cadmium poisoning 3. d- Penicillamine Used for Cu poisoning and Wilson disease 4. Fe chelating agentsQ Desferioxamine Injectable DOC for acute Iron poisoning Deferipirone Oral Used for chronic Iron over load Previous Years Questions Q1. Which of the following is an adverse effect of orlistat? A. Suicidal tendancy B. Steatorrhea C. Weight gain D. Hyperglycemia Q2. Longest acting phosphodiesterase inhibitor among the following drugs is? A. Sildenafil B. Vardenafil C. Tadalafil D. Phentolamine Q3. Which of the following is FDA-approved drug for long term treatment of obesity? A. Sibutramine B. Liraglutide C. Metformin D. Fenfluramine Q4. An 11-year-old boy presented to emergency with vom iting. Parents gave history of consuming 10-15 tablets of ferrous sulphate a day before. What is the antidote of iron for treatment of this patient? A. Dimercaprol B. Desferrioxamine C. d- Penicillamine D. Activated charcoal Q5. A patient presented with hyperkalemia. Which of the following drugs can cause intracellular movement of and thus decrease in extracellular potassium levels? A. Atropine B. Lactic acid C. Epinephrine D. Glucagon Answers 1. - B 2. - C 3. - B 4. - B 5. - C