Pharma RR cerebellum.pdf

Pharmacology Quick Revision Notes  Chapter - 1 General Pharmacology Pharmacology is the science dealing with drugs. ↓ Absorption → ↓ Bioavailability Two branches: 2. First Pass metabolism/Pre systemic metabolism 1. Ph...

Pharmacology Quick Revision Notes  Chapter - 1 General Pharmacology Pharmacology is the science dealing with drugs. ↓ Absorption → ↓ Bioavailability Two branches: 2. First Pass metabolism/Pre systemic metabolism 1. PharmacoKinetics → Effect of Body on Drug ↑ First Pass metabolism → ↓ Bioavailability 2.PharmacoDynamics → Effect of Drug on Body ↓ First Pass metabolism → ↓ Bioavailability Note: If we give a drug by IV route, bioavailability is PHARMACOKINETICS 100%Q Aka ADME Study Plasma Concentration Vs Time Graph –– Absorption –– Distribution –– Metabolism –– Excretion 1. Absorption It is the movement of drug from site of administration to blood. Maximum concentration Should lie between MTC Lipid Solubility is the most important factor in Cmax obtained by a particular and MEC absorption.Q dose Time in which plasma When The Medium Is Same, Then The Drug Will Cross Tmax concentration becomes Tells Rate of absorption DRUG MEDIUM FORM SOLUBILITY CROSS maximum Acidic Acidic Non ionized Lipid Soluble  Total area covered by Tells Extent of AUC Basic Basic Non ionized Lipid soluble  graphQ absorption Acidic Basic lonized Water Soluble x Basic Acidic lonized Water Soluble x 2. Distribution Distribution is a measure of amount of drug in tissues Bioavailability after absorption in the systemic circulation It is the fraction of given dose that reaches the systemic circulation in unchanged form 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 Factors affecting: Dialysis not useful in poisoning 1. Absorption Less Filtration → Absorption → ↑ Bioavailability  3 Pharmacology Volume of Distribution (Vd)Q Enzyme InducersQ Enzyme inhibitorsQ Amount given G -Griseofulvin Vit -Valproate Vd = Plasma concentration P -Phenytoin K -Ketoconazole Volume of Distribution (Vd) ∝ Amount of Drug in Tissues R -Rifampicin Can’t -Cimetidine More Vd → More distribution S -Smoking Cause -Ciprofloxacin Loading Dose [LD] Cell -Carbamazepine Enzyme -Erythromycin Phone -Phenobarbitone Inhibition -Isoniazid Initial high dose given to start the action Cytochrome p450 Enzymes LD = Vd x Target Plasma Concentration These are one type of microsomal enzymes. Maintenance DoseQ CYP3A4 CYP2D6 CYP2C19Q Repeated doses given to maintain the plasma concentration. C : Cyclosporine 2 : b-Blockers Clopidogrel MD = CL x Target PC T : Tacrolimus D : Anti-Depressants S : Statins 6 : Anti-Anthythmies 3. Metabolism C : CAT (except amiodarone) Aim of Metabolism → To Make a Drug Water Soluble (Polar) (Cisapride, PHASE I REACTIONSQ PHASE II REACTIONSQ Mostly catabolic Reactions Mostly anabolic reactions Astemizole, Includes Includes Terfenadine) CYP2C9Q Oxidation (MC) Glucuronidation (MC) A :Amiodarone Warfarin Reduction Glutathione conjugation N :Navirs Phenytoin Hydrolysis Acetylation Cyclization Methylation Clopidogrel Deamination Sulfate conjugation – CYP2C19 PPI Purpose of Phase I → Expose the Functional Group on the drug Active Purpose of Phase II → Makes the drug water soluble Therefore, PPIs are avoided with clopidogrel 4. Excretion Enzymes Divided into Microsomal and Non-microsomal Microsomal Non-microsomal Present in smooth Present outside SER endoplasmic reticulum Can be induced or Cannot be induced or inhibited inhibited 4 Cerebellum Quick Revision Notes Glomerular Filtration Formula of Half-life: Lipid soluble as well as water soluble drugs can be 1 0.693 filtered t = 2 K Filtration is inversely proportional to Plasma Protein binding (where, K is elimination rate constant) CL As K= Tubular Reabsorption Vd 99% of GFR is reabsorbed So, 1 Vd –– Lipid soluble drugs reabsorbed t = 0.693 X 2 CL –– Water soluble drugs excreted Order of Kinetics First order kinetics Zero order kineticsQ → Fraction is constant → Amount is constant R a PC R = Constant CL = Constant CL a 1/ PC Tubular Secretion t½ = Constant t½ a PC Due to pumps/transporters in proximal tubules Majority of drugs follow First Order Kinetics These transporters are Saturable (One drug can be transported at one time) Drugs Following Zero Order Kinetics areQ Probenecid prolongs action of penicillins by inhibiting Zero → Zero order Kinetics tubular secretion W → Warfarin A → Alcohol/Aspirin Kinetics of Elimination T → Theophylline T → Tolbutamide Half Life [t1/2] Power → Phenytoin It is the time in which plasma concentration of a drug becomes half. PHARMACODYNAMICS: Half-life is constant in first order kinetics. 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. Question: t1/2= 6hrs, after 1 day Enzyme inhibitionQ How much drug remains in body → 6.25% Km Vmax How much drug eliminated from body →100-remaining→ 93.75% Competitive ↑ - Importance of t ½: Non competitive - ↓ Dose cannot be calculated Lineweaver Burke Plot: Dosing Interval/ Frequency can be known 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 1. lonotropic Receptors If lines intersect at X-axis, it is non-competitive The receptors present on ion channels are known as inhibition ionotropic receptors. If lines intersect at Y-axis, it is competitive Fastest acting receptors inhibition 2. Enzymatic Receptors These are present on cell membrane with intracellular and extracellular ends. Classification of DrugsQ Drug binds outside and enzyme is activated inside and action is produced Drug Intrinsic Activity Aka Tyrosine Kinase Receptors 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 3. G-Protein Coupled Receptors [GPCR] Classification of Receptors Works by one out of the 3 mechanisms By changing the level of cAMP Can act through Ca2+ Can open the ion channels 6 Cerebellum Quick Revision Notes Types of G proteins 1. Potency 2. Efficacy Second/Third Type Mechanism 3. Slope messenger GS Stimulate adenylate cyclase ↑ cAMP Gi Inhibit adenylate cyclase ↓ cAMP IP3 Gq Convert PIP2 to IP3 and DAG DAG Calcium 4. Intracellular Receptors A. Cytoplasmic Receptors B. Nuclear Receptors Potency Only Lipid soluble drugs acts through these receptors 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 Thus, whether a drug binds the cytoplasmic H - Height tells aboutQ receptors or the nuclear receptors, it will finally work through DNA (nuclear mechanism) E - Efficacy These are also called nuclear recetor superfamilty L - Left side drugs are more These are slowest acting receptors. P - Potent Receptors Examples 1. Ionotropic GABAA, NMDA, NN, NM, 5HT3 2. Enzymatic Cytokines, Prolactin, Insulin, GH 3. Intracellular A. Cytoplasmic Vit D, Glucocorticoids, Mineralocorticoids B. Nuclear Vit A, Thyroid hormones, Sex hormones 4. GPCR Most others C → Most efficacious (Highest curve) Log Dose Response Curve (Log DRC) S-shaped curve [Sigmoid Curve) D → Least efficacious (Lowest curve) Clinically more useful than DRC D → Most potent (Most left) 3 important parameters obtained from log DRC: B → Least potent (Most right)  7 Pharmacology Quantal DRC Clinical Trials For All or None phenomenon, where grade of response Testing of drugs in humans is called clinical trials cannot be plotted. Licensing Authority to give approval for a new drug Percentage of subjects responding are kept on Y-axis in USA is FDA whereas in India it is DCGI (Drug Tells about effect of a drug in population Controller General of India) Q 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 Q 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, Q 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. Phase Zero Clinical Trials Misbranded drug: If a drug is not labelled in prescribed manner or its label contains any Micro-dosing study statement which makes any false claims for the It is conducted on humans drug. Maximum amount of drug given is 100 mcg or Adulterated drug: If it contains filthy, patrid or (1/100)th of Human Equivalent Dose, whichever is decomposed substances. lower Radiolabeled substances are added with this sub therapeutic dose to know the Pharmacokinetics of the drug. It is not mandatory Q 8 Cerebellum Quick Revision Notes Pregnancy Categories: Fixed Dose Combinations (FDC): Drugs are categorized into 5 groups according to safety When two or more drugs are combined to- in pregnancy gether in a particular ratio. Category Special points Advantages: Disadvantages: A Safest in pregnancy Compliance May be used irrationally. B improves If adverse effect occurs, it C One drug may cannot be ascribed to one drug. D reduce the adverse Drugs with different X Contra-indicated in pregnancy e.g. ThalidomideQ effects of the pharmacokinetics cannot be Note: other drug combined. Efficacy may Dose of one drug cannot be Schedule X drugs and category X drugs are totally increase altered independently as per different. Cost may decrease requirement. Schedule X include narcotic and psychotropic drugs e.g. ketamine. Prescription Writing Category X contain teratogenic drugs like thalidomide Prescription is the written order by the doctor to the pharmacist to dispense some medication.Q Schedule H drugs require prescription of a RMP. SAFE AND UNSAFE DRUGS IN PREGNANCY Condition Drugs safe in Drugs to beQ Pregnancy avoided in Pregnancy Hypertension Labetalol, ACE Inhibitors and Methyldopa ARBs Anti-coagulants Heparin Warfarin Bipolar disorders Anti-psychotics Valproate (Contra- indicated) Lithium (Avoid) Anti-thyroid Propylthiouracil Carbimazole (1st trimester) Note: Anti-microbials Penicillins, Tetracyclines Cephalosporins Quinolones Without date and signature (initials), the prescription is invalid. Macrolides Aminoglycosides Anti-Epileptics Levetiracetam Valproate Drug name should never be written in short form (e.g., write paracetamol, not PCM) Lamotrigine Abbreviations like OD, BD, HS should not be usedQ Enteric Coating of Drugs: In dose of drug This is a coating that dissolves in alkaline medium –– Leading zeros should always be mentioned only. (e.g., 0.5 mg is correct but.5 mg is wrong) It can be used for –– Trial zeros should never be mentioned (e.g., 5 –– Protecting the acid labile drugs from gastric mg is correct but 5.0 mg is wrong) acid, e.g., proton pump inhibitors. –– Microgram should be written as mcg not μg.Q –– It can protect gastric mucosa from irritant drugs e.g. NSAIDS –– It increases the absorption of drugs that are preferentially absorbed distal to stomach.  9 Pharmacology Previous Years Questions Q1. Which of the following factor in PC vs time graph is Q8. Which of the following drugs follow zero order a measure of extent of drug absorption of a drug? kinetics? A. Area under the curve B. Half life A. Phenytoin B. Diclofenac C. Cmax D. Tmax C. Morphine D. Propranolol Q2. Rate of administration of a drug is equal to rate Q9. Identify the type of inhibition from the given graph 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 A. Competitive B. Non-competitive Q4. High plasma protein binding of a drug results in: C. Un-competitive D. Allosteric A. Decreased glomerular filtration Q10. True about non-competitive inhibition is B. High volume of distribution A. Km remains same, Vmax decreases C. Lowers duration of action B. Km increases, Vmax remains same D. Less drug interaction C. Km decreases, Vmax increases Q5. A patient with stroke was started on clopidogrel. D. Km increases, Vmax increases He developed another episode of stroke 6 months later. Which of the following is the likely cause? Q11. Identify the missing substance X marked in the A. Rapid metabolism by CYP 1A2 box in the given diagram 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 A. G protein B. Protein C Q7. Elimination rate constant of a drug is 0.05/hr. What is its half life? C. Cyclic AMP D. Calcium A. 6.5 hr B. 20 hr C. 13.9 hr D. 8 hr Answers 1. - A 3. - A 5. - B 7. - C 9. - A 11. - C 2. - B 4. - A 6. - A 8. - A 10. - A 10 Cerebellum Quick Revision Notes Q12. Which of the following statement is correct A. 1 B. 2 regarding the given graph? 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 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. Type of stimulatory G protein in PIP2-Phospholipase activation pathway is A. Gs B. Gi C. Gq D. Go A. Drug A is most potent Q14. Drug acting via tyrosine kinase receptor is B. Drug A and B have equal efficacy but B is more A. TRH B. TSH potent than drug A C. Insulin D. MSH C. Drug C is least potent Q15. Which of the following drugs act through D. Drug B has more potency but less efficacy than drug A intracellular receptors? Q19. Which of the following statement is correct about A. Thyroxin B. Glucagon clinical trials? C. Epinephrine D. Parathyroid hormone A. New drug application is filed with Phase 2 clinical trials Q16. Find therapeutic index of a drug from the information given below in the graph 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 14. - C 16. - C 18. - A 13. - C 15. - A 17. - A 19. - B  11 Pharmacology Q20. New drug application is filed after which phase of Q25. Variation in drug responsiveness to a particular clinical trials? dose of the drug in different individuals can be obtained from: A. Phase 1 B. Phase 2 A. Graded Dose Response Curve C. Phase 3 D. Phase 4 B. Efficacy Q21. Manufacturer of a drug company labels the drug C. Potency contains 500 mg paracetamol. On quantitative analysis by the authorities, it was found to contain only 200 mg D. Quantal Dose Response Curve of drug. According to drugs and cosmetics act 1940, this type of drug is known as? Q26. Which of the following statement is true regarding Fixed Dose Combination of drugs? A. Spurious drug B. Adulterant drug A. Adverse effect of one drug may be reduced by the C. Unethical drug D. Misbranded drug other drug Q22. Identify the true statement regarding Clinical B. Two drugs with different pharmacokinetics can be Trials: combined easily A. Phase 1 is done to determine efficacy in patients C. Dose of one drug can be altered independently as per requirement B. Healthy volunteers are recruited for the first time in Phase II D. Adverse effect can be ascribed to a single drug Q27. Which of the following drug must be sold by C. Randomized Controlled Trials in patients is done in retail only production of a prescription by a registered Phase III medical practitioner? D. Phase IV is Pharmacokinetics study in animals A. Schedule H B. Schedule G C. Schedule X D. Schedule M Q23. All of the following are advantages of enteric coated tablets except Q28. As an Indian medical intern, which of the following A. It increases the half-life of the drug is the correct format for prescription of alprazolam? A. Tablet alprazolam 0.5 mg once a day before B. It protects acid labile drugs from gastric pH bed time for 7 days C. It increases the absorption of drugs that are B. Tablet alprazolam 0.5 mg HS for 7 days preferentially absorbed distal to stomach. C. Tablet alprazolam 500 mcg one tablet OD D. It protects stomach from irritant drugs for 7 days D. Tablet alprazolam ½ mg tablet HS daily 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 Answers 20. - C 22. - C 24. - A 26. - A 28. - A 21. - D 23. - A 25. - D 27. - A  Chapter - 2 Autonomic Nervous System Origin: Neurotransmitters: It works on cholinergic receptors Location Neurotrans- mitter Preganglionic parasympathetic ACh Preganglionic sympathetic ACh Postganglionic parasympathetic ACh Postganglionic sympathetic At all places NA At sweat glands ACh Actions: Location Parasympathetic Sympathetic Heart ↓↓ +++ Bronchus Bronchoconstriction Bronchodilation Cholinergic Receptors GIT Diarrhea Constipation Nicotinic Receptor Muscarinic Receptor NN→ Ganglia M1 → Stomach: ↑HCl Bladder Contract Relax NM→ NMJ (require M2 → Heart: ↓ HR, ↓ Conduction Glands ↑ Secretions ↓ Secretions optimal stimulation) M3 → Bronchus : BC Pupil Miosis Mydriasis GIT : ↑ Peristalsis Sexual system Erection Ejaculation Bladder : ↑ Contraction Glands : ↑ Secretions PARASYMPATHETIC SYSTEM Pupil : Miosis Major neurotransmitter is ACh  13 Pharmacology CHOLINERGIC DRUGS: Organophosphate Poisoning: Drugs stimulating the parasympathetic system can be: Clinical features: Receptor Feature Directly Acting Cholinergic Drugs: stimulated DRUG ACTS ON ACTION INDICATION M1 Aciditiy Pilocarpine Pupil [M3] Miosis Angle closure M2 Bradycardia and Hypotension glaucoma Q M3 Pin point pupil Indirectly Acting Cholinergic Drugs: ↑ Secretions These drugs act by inhibiting AChE. Diarrhea These may be reversible or irreversible AChE Urination inhibitors. Bronchoconstriction Reversible AChE inhibitors are used clinically M1, M2, M3 Coma whereas irreversible AChE inhibitors are toxic. NM Muscle weakness Reversible AChE Inhibitors: 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. Uses of Neostigmine Q 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 Irreversible AChE Inhibitors (endrin) poisoning. Include 2. AChE Reactivators (Oximes)Q Organophosphates - Malathion Pralidoxime [PAM] Parathion Carbamates - Carbaryl Di Acetyl Monoxime [DAM] Propoxur Not DOC Only effective in OP Poisoning PAM acts only peripherally, DAM has both central as well as peripheral actions. 14 Cerebellum Quick Revision Notes ANTICHOLINERGIC DRUGS Organ Receptor Drugs Uses blocked Pirenzepine Stomach M1 Peptic ulcer Telenzepine Bradycardia Heart M2 Atropine (DOC) AV block Ipratropium Bronchial asthma Bronchus M3 Tiotropium COPD S- Solefenacin O- Oxybutynin Overactive bladderQ Bladder M3 F- Flavoxate T - Tolterodine BladDAR- DARifenacin Fundoscopy Atropine Refraction testing Homatropine Iridocyclitis Cyclopentolate EYE M3 Tropicamide Longest acting: Atropine DOC in children–Atropine eye ointment Shortest acting: Tropicamide ATROPINE POISONING: SYMPATHETIC NERVOUS SYSTEM (ANTICHOLINERGIC POISONING) Major neurotransmitter is nor-adrenaline Patient has a history of taking some wild fruit (Dhatura/Belladona) and presents withQ Adrenergic Receptors D – Dry mouth, Delirium a1 a2 H – Hyperthermia Location Action Presynaptic A – Agitation Blood vessels Vasoconstriction receptor T – Tachycardia Eye Mydriasis → Acts like brake to U – Urinary Prostatic ↓ Outflow sympathetic system R – Retention urethra A – Accommodation lost (Blurred vision, Photophobia) DOC for treatment of atropine poisoning is physostigmine.Q  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 Tremors spindle Liver ↑ Blood sugar Effect on blood vessels It is an addictive drug A1 -> C α1 – Cause vasoconstriction Q –– Shows tactile hallucinations (cocaine bugs): B2 -> D β2 – Cause vasodilation Scratching of skin Effect on metabolism: –– Cause palatine perforation Sympathetic system protects from hypoglycemia by –– Overdose characterized by two mechanisms: ƒƒ Agitation Warning symptoms Hypoglycemia reversal ƒƒ Ulcers or scratch marks on skin Tachycardia (b1) By changing metabolism (b2) ƒƒ Sympathetic symptoms (Tachycardia, Palpitations (b1) - ⊕ Gluconeogenesis Mydriasis, Hypertension, MI) Tremor (b2) - ⊕ Glycogenolysis Sweating (M3) - ⊝ Glycogenesis Note: Cocaine does not cause bradycardia since it is a sympathetic drug. Directly Acting Drugs Beta Blockers cause (in diabetic patients) 1. Masking of warning symptoms 1.CATECHOLAMINES 2. Prevent reversal of hypoglycemia – Not effective orally So, b blockers are contraindicated in diabetic Endogenous Exogenous patients. Adrenaline (a1, a2, b1, b2) Dobutamine (b1) Sweating is only reliable symptom of hypoglycemia in diabetics on b blocker medication.Q NA (a1, a2, b1) Isoprenaline (b1, b2) Dopamine (D1, b1, a1) Fenoldopam (D1) ADRENERGIC DRUGS: Uses of Catecholamines These can be divided into: Adrenaline Indirectly Acting Drugs 1. Anaphylactic Shock Directly Acting Drugs DOC is Adrenaline Indirectly Acting Drugs Route of choice is I.M. or S.C. COCAINE - It acts by inhibiting reuptake of NAQ Concentration is 1:1000 (0.5 ml)Q 2. Cardiac Arrest It is a local anaesthetic CPR is done first –– All LA cause vasodilation except cocaine Adrenaline is useful –– Cocaine cause vasoconstriction and Concentration is 1:10,000Q hypertension Preferred routes are IV > Intraoseous > ET 16 Cerebellum Quick Revision Notes Nor-Adrenaline Note: Beta-2 agonists can cause following adverse DOC for septic shock effects: Effect is monitored by checking mean blood pressure –– T - Tremors –– T - Trachycardia Dopamine –– T - T-wave changes in ECG (due to hypokalemia) Acts onQ –– Pulmonary edema - by ritodrine Receptors Dose (mcg/ Organ Action –– However, b2 agonists do not cause kg/min) hypoglycemia.Q D1 10 Blood Vasoconstriction These can be non-selective (α1 + α2) blockers or selective vessels α1 blockers Uses Non-selective α blocker α1 Blocker 1. CHF 1. Used in severe 1. Used in mild to 2. Shock + Oliguria [DOC] hypertension moderate hypertension Dobutamine 2. Can cause severe 2. Cannot cause severe Mainly b1 agonist tachycardia tachycardia Used for CHF Fenoldopam Non-Selective α Blockers Only D1 agonist Irreversible Reversible Used for hypertensive emergencies Phenoxybenzamine Phentolamine, Tolazoline Isoprenaline Used for Used for ↑ SBP but ↓ DBPQ – Pheochromocytoma – Cheese Reaction Maximum increase in pulse pressure – Clonidine withdrawal 2. NON-CATECHOLAMINES Selective α1 Blockers Prazosin Stimulates Drugs Action Terazosin a1 Phenylephrine Mydriasis without eye drops cycloplegia Doxazosin Methoxamine → Vasoconstriction → Used Alfuzosin Mephentermine in shock Uses Xylometazoline → Nasal decongestants BPH (Due to a1A blockade) Oxymetazoline Scorpion sting (D.O.C is Prazosin) Naphozoline a2 Clonidine → Brake for sympathetic system Adverse Effect First Dose (Postural) Hypotension Methyldopa → Used for hypertension → a1 blockers always started at bed-time.Q b2 Salbutamol → Bronchodilation Terbutaline → Used for asthma by Types of α1 receptors inhalational route α1A α1B/1D Salmeterol On Prostatic Urethra On Blood Vessels Formoterol TAMSULOSIN Ritodrine → Tocolytic SILODOSIN Isoxsuprine → Used for preterm labour No postural hypotension b3 Mirabegron Overactive bladder DOC for normotensives with BPH  17 Pharmacology Benign Prostatic Hyperplasia: (BPH) Indications Cardiac Uses α1A blockers 1. Hypertension Tamsulosin - Stops the dynamic component and do 2. Classical Angina [C/I in Variant angina] not affect the size of prostate i.e they are only for the symptoms of BPH but do not stop the growth 3. MI of prostate. 4. Chronic CHF [C/I in acute CHF] 5. Arrhythmia 5-α reductase inhibitors: Non-Cardiac Uses Finasteride - Stops the conversion of Testosterone to DHT which control/stops the growth of Prostate Play - Performance anxiety (DOC : Propranolol) in BPH (Static Component). The – Thyrotoxicosis (DOC : Propranolol) 2. BETA (β) BLOCKERS G – Glaucoma (Timolol is used) A – Akathisia (DOC : Propranolol) Beta-1 + Beta-2 # (First Beta-1 # (Second M – Migraine prophylaxis (DOC : Propranolol) Generation) Generation) Cardiac and non-cardiac Only cardiac uses E – Essential tremors (DOC : Propranolol) uses Contraindicated in Asthma, Relatively safe Adverse Effects and Contra-indications DM and PVD Due to β1 Blockade 1. Beta-1# or Cardio-Selective or 2nd 1. ↓ Rate → Bradycardia (C/I in Sick sinus syndrome) Generation Beta # 2. ↓ Conduction → AV Block New → Nebivolol 3. ↓ Contractility → Acute CHF Beta → Betaxolol Due to β2 Blockade Blockers → Bisoprolol 1. Asthma Act → Acebutolol 2. Peripheral vascular Disease Exclusively → Esmolol 3. Diabetes mellitus At → Atenolol Myo → Metoprolol 4. Variant angina. Cardium → Celiprolol GLAUCOMA → These are relatively safe in Asthma, PVD & DM → Glaucoma is characterized by ↑ IOP: It may be due 2. Intrinsic Sympathomimetic Activity [ISA] or to Partial Agonists –– ↑ Aqueous humor production → Less chances of causing severe bradycardiaQ –– ↓ Aqueous humor drainage Contain → Celiprolol Partial → Pindolol Agonist → Alprenolol Activity → Acebutolol 18 Cerebellum Quick Revision Notes 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. DRUG OF CHOICE ANS PRACTICALS 1. Ileum graphQ - POAG – Latanoprost - Angle closure glaucoma – Acetazolamide - Acute congestive glaucoma – Mannitol  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 20 Cerebellum Quick Revision Notes Previous Years Questions Q1. Which of the following action is expected on and tears were present. The boy had involuntary stimulation of muscarinic receptors? urination and diarrhea. On examination, the heart rate was 58 beats per minute and blood pressure was 80/60 A. Erection mm Hg. Which of the following is the drug of choice for treatment of this patient? B. Ejaculation C. Increased contraction of cardiac muscles A. Atropine D. Bronchodilation B. N-acetylcysteine C. Naloxone Q2. A farmer presented with pin point pupil and increase in secretions. Likely poisoning is D. Physostigmine A. Organophosphate poisoning Q7. A study was conducted to see the effect of different drugs on isolated mammalian intestinal tissue B. Dhatura poisoning in Dale’s organ bath. The following graph is obtained. C. Opioid poisoning Which of the following is the likely drug? 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. A. Acetylcholine Ten vials of antivenom were administered intravenously B. Barium chloride but the patient is still having difficulty in swallowing, ptosis and respiratory distress. What should be the C. Adrenaline next line of management? D. KCl A. Atropine and neostigmine Q8. An experiment on dog blood pressure was done B. Nebulizer with salbutamol by adding different drugs. The drugs added and the C. IV hydrocortisone effects are as shown in the given figure. This experiment is done to demonstrate the 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 Answers 1. - A 3. - A 5. - A 7. - C 2. - A 4. - A 6. - A 8. - B  21 Pharmacology A. Muscarinic action of ACh A. Cocaine B. Cannabis B. Nicotinic action of ACh C. LSD D. Heroin C. Potentiation of ACh Q15. Which dose of dopamine act preferably on beta-1 D. Antagonistic action of ACh receptors? A. Less than 2 mcg/kg/min Q9. After eating an unknown plant, A child presented to emergency in comatose state. The pupils were dilated B. 2-10 mcg/kg/min and skin was dry. Body temperature is raised and heart rate is high. These signs and symptoms can occur with C. 10-20 mcg/kg/min the intake of which of the following substance? D. More than 20 mcg/kg/min A. Dhatura B. Poppy seeds Q16. A patient was on metoprolol therapy for C. Mushroom D. Cannabis hypertension. He was also administered verapamil. Which of the following is likely to happen with above Q10. Topical atropine is not given in combination therapy? A. Acute congestive glaucoma A. Torsades de pointes B. Corneal ulcer B. Ventricular tachycardia C. Malignant glaucoma C. Ventricular fibrillation D. Acute anterior uveitis D. Bradycardia with AV block Q11. All of the following are Side effects of Ritodrine Q17. A 65 years old patient presented with dribbling of except? urine with urgency. He was started on prazosin therapy but the patient developed postural hypotension. Which A. Hypoglycemia B. Tachycardia of the following is the better alternative drug for this patient? C. Hypotension D. Pulmonary edema A. Terazosin B. Tamsulosin Q12. Which of the following is the action of dopamine at low doses? C. Timolol D. Phenoxybenzamine A. It increases renal blood flow Q18. Beta blockers are avoided in all of the following conditions except B. It causes vasoconstriciton C. It has positive chronotropic action A. Glaucoma D. It causes hypotension B. Peripheral vascular disease C. Diabetes mellitus Q13. A lady was stung by many bees. She developed breathing difficulty and hypotension. Drug used for D. COPD treatment of this condition is? Q19. Hypertension and pulmonary edema associated A. Adrenaline B. Nor-adrenaline with scorpion sting is managed by: C. Dopamine D. Isoprenaline A. Carvedilol B. Prazosin Q14. A drug addict patient presented with agitation C. Spironolactone D. Phentolamine and ulceration on skin. The patient had severe itching and scratch marks on the body. On examination there is Q20. Which of the following is a contraindication to the presence of tachycardia, mydriasis and hypertension. use of Beta Blockers? Likely substance responsible for these symptoms is? A. Glaucoma B. Tachycardia C. Bronchial asthma D. Hypertension Answers 9. - A 11. - A 13. - A 15. - B 17. - B 19. - B 10. - A 12. - A 14. - A 16. - D 18. - A 20. - C 22 Cerebellum Quick Revision Notes Q21. A known patient of bronchial asthma was started Q24. Anti-glaucoma drug that acts by increasing on treatment with an anti-glaucoma drug. During the uveoscleral outflow is course of treatment, asthma worsened. Which drug is likely responsible for these symptoms? A. Latanoprost B. Timolol A. Timolol B. Brimonidine C. Pilocarpine D. Dorzolamide C. Latanoprost D. Pilocarpine Q25. A patient with bronchial asthma presents with raised intraocular pressure. Treatment of open angle Q22. A patient had symptoms of redness and glaucoma in this patient is photophobia. On examination, cells were present in anterior chamber with keratic precipitates. Intraocular A. Latanoprost B. Alprostadil pressure was measured to be 38 mm Hg. Which of the C. Gemeprost D. Carboprost following anti-glaucoma drug should be avoided? A. PG analogues Q26. Which anti-glaucoma drug acts by increasing trabecular outflow? B. Beta blockers A. Netarsudil B. Timolol C. Mannitol C. Acetazolamide D. Brimonidine D. Carbonic anhydrase inhibitors Q23. Drug capable of causing ocular hypotension with apnoea in infants is: A. Acetazolamide B. Latanoprost C. Brimonidine D. Apraclonidine Answers 21. - A 23. - C 25. - A 22. - A 24. - A 26. - A  Chapter - 3 Autacoids - Have autocrine effects [Local effects] H1 Blockers - Based on chemical Structure 1st Generation 2nd Generation Peptide Autacoids Amine Autacoids Lipid Autacoids Cross BBB, cause sedation Do not cross BBB, no → Angiotensin → Histamine → Prostaglandins sedation → Bradykinin → 5-HT → Leukotrienes Have Anti-cholinergic action No Anti-cholinergic action → Thromboxane → Anticholinergic S/E occur Useful for allergy and Useful only for allergy HISTAMINE Possess : Prophylaxis of Receptors motion sickness Anti : Akathisia Location Action Blockers Cholinergic : Common Cold H1 CNS Allergy First and Property : Parkinsonism Bronchus second (Drug induced) Stimulates RAS Generation Promethazine FexofenadineQ Promote Drugs Terfenadine metabolite wakefulness Loratidine H2 Stomach Secrete Acid Ranitidine Cetirizine Cimetidine H3 PreSynaptic BRAKE H3 Inverse Agonist Tiprolisant [Pitolisant] Used for Narcolepsy H4 WBC Chemotaxis 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 DOC for Eletriptan Rizatriptan Acute Severe Migraine 5HT2A/2C Brain Blockers Clozapine , Olanzapine Atypical Antipsychotics 5HT3 CTZ Emesis Blockers Ondansetron Granisetron DOC for vomiting due to Tropisetron Dolasetron Chemotherapy PalonosetronQ Radiotherapy Post-operativeQ 5HT4 GIT Prokinetic Agonist Cisapride , Mosapride, As prokinetics for GERD Prucalopride 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. General Effects Q 1. Lasmiditan (DITANS) Fever Stimulates 5HT1F receptor and decreases CGRP Pain release. Inflammation This prevents the vasodilation and neuronal inflammation. 2. Platelets Effective orally. TXA2 → Aggregation It is recently approved for acute attacks of PGl2 → Inhibition of aggregation migraine. 3. Heart Advantage over triptans is that it does not induce Ductus Arteriosus is kept open by PGE1 peripheral vasoconstriction. PDA [Patent ductus Arteriosus] is treated by 2. Monoclonal Antibodies Against CGRP NSAIDs like Approved for prophylaxis of migraine. –– Aspirin Given by injectable route. –– Indomethacin –– Erenumab –– Ibuprofen (DOC) –– Fremanezumab –– Galcanezumab 4. Uterus –– Eptinezumab PGs Contract upper segment of uterus Q Used for abortion (Misoprostol is used) 3. CGRP Antagonist: (GEPANTS) 5. Stomach Used for acute attack PGE2 protect the stomach from peptic ulcer disease Effective orally For NSAID Induced Peptic Ulcer Disease Drugs are –– Most specific drug is MisoprostolQ –– Olcegepant –– DOC is proton pump inhibitors –– Rimegepant –– Ubrogepant 6. Eye PROSTAGLANDINS PGF2α → ↑ Uveo scleral outflow → Latanoprost → DOC for Primary Open Angle GlaucomaQ  25 Pharmacology NON-STEROIDAL ANTI- - Valdecoxib INFLAMMATORY DRUGS (NSAIDs) - Parecoxib COX 1 COX-2 - Lumiracoxib Constitutive Enzyme Inducible enzyme These have lesser risk of causing PUD Present normally at most Present normally in These increase the risk of MI and stroke places Kidney Endothelium - Etoricoxib Longest acting CNS - Rofecoxib and Valdecoxib Withdrawn because of MI and stroke NSAIDS act by inhibiting COX. These may be: - Parecoxib is given by Parenteral route Non-Selective COX Inhibitors Selective COX-2 Inhibitors - Lumiracoxib is withdrawn Due to Liver toxicity ↑ Risk of PUD Less risk of PUD GOUT Non-Selective COX Inhibitors It is characterized by increase in serum uric acid. Drugs Acute Gout - Aspirin : Irreversible COX inhibitor 1. DOC : NSAIDs (except aspirin and paracetamol) (Antiplatelet), ↑Uric acid 2. Steriods : If NSAIDs do not work - Paracetamol : COX - 3 inhibitor, safe in CKD 3. Colchicine (Most effective drug):Q - Ibuprofen : DOC for PDA - Can cause myopathy and diarrhea - Diclofenac : Partial COX-2 selective - Inhibit granulocyte migration - Indomethacin : Sedation is adverse effect - Piroxicam : Longest acting NSAID Chronic Gout - Nimesulide : Not used in children (hepatotoxic) Three types of drugs can be used in chronic gout. - Ketorolac : Given IV – Drugs decreasing production of uric acid – Drugs increasing excretion of uric acid (Uricosuric agents) – Drugs increasing metabolism of uric acid Proteins / Purines Xanthine Xanthine oxidase 1 Uric acid Excretion 2 In birds Uricase 3 Allantoin Selective COX 2 Inhibitors Drugs - Celecoxib - Rofecoxib 26 Cerebellum Quick Revision Notes 1. ↓ Formation 2. ↑ Excretion 2. Biological DMARDs: AllopurinolQ Probenecid i. Drugs Inhibiting TNF-a:Q Inhibit xanthine oxidase Sulfinpyrazone - All are injectable DOC for chronic gout Lesinurad Febuxostat A Adalimumab → Plenty of fluids should C Certolizumab Inhibit xanthine oxidase be taken E Etanercept 3.↑ Metabolism Inhibitor lnfliximab Rasburicase → Recombinant uricase Goli Golimumab → ↑ Risk of infections. Pegloticase → Long acting uricase These are fastest urate lowering agents for tumor → Contra-indicated in T.B. and Hepatitis B lysis syndromeQ → Apart from R.A., these drugs can be used for Crohn’s disease as well as Psoriasis RHEUMATOID ARTHRITIS NSAIDs and Steroids DMARDs or SAARDs ii. IL - 1 Receptor Antagonist:Q Slow down the disease ANAKINRA ↓ Pain and lnflammation progression No effect on disease –– A - 1st letter Progression –– KIN - Interleukin Fast acting Slow acting –– R - Receptor –– A - Antagonist 1. Conventional DMARD: DMARD of choice in iii. IL - 6 Receptor Antagonists:Q Cute and Chloroquine pregnancy Tocilizumab Used for Cu poisoning/ p Penicillamine → 1st IL- 6 targeted monoclonal Antibody. Wilson’s disease → Approved for treatment of cytokine release A Azathioprine syndrome also. G Gold salts Sarilumab L Leflunomide Fastest acting DMARDQ → Used for rheumatoid arthritis S - Six Inhibitors of Tofacitinib I AR - R.A. JAK Baricitinib MAB - Monoclonal antibody DOC, Needs LFT Malika Methotrexate Monitoring iv. Co-stimulation InhibitorsQ DOC for ulcerative Abatacept Sherawat Sulfasalazine colitis Inhibit the interaction of T-cell and Antigen Presenting Cells (APC).  27 Pharmacology Previous Years Questions Q1. Most specific antiemetic for Chemotherapy induced Q8. A 60 year old female with renal disease was vomiting is: admitted for pyelolithotomy. Post operative analgesic of choice in this patient is? A. Doxylamine B. Tegaserod A. Diclofenac B. Indomethacin C. Granisetron D. Domperidone C. Naproxen D. Acetaminophen Q2. Buspirone is a drug used in chronic anxiety. It produce its action by acting on which of the following Q9. Which of the following is the fastest urate receptors? lowering therapy in tumor lysis syndrome to prevent renal damage? A. 5HT1A B. 5HT1B A. Allopurinol B. Febuxostat C. 5HT2 D. 5HT3 C. Rasburicase D. Furosemide Q3. A boy is planning to travel by bus. Which of the following drug can be used to prevent motion sickness Q10. A female patient presented with pain and redness in this person? in great toe. Serum uric acid level is 9.6 mg/dL. Apart from prescribing analgesics for relieving pain, the A. Promethazine B. Cetrizine physician prescribed a drug which can decrease the C. Loratidine D. Fexofenadine formation of uric acid. Which of the following enzyme is likely to be inhibited by this drug? Q4. Drug of choice for prophylaxis of migraine is A. Xanthine oxidase A. Propranolol B. Imipramine B. Thymidylate synthase C. Flutamide D. Flunarizine C. Phosphpribosyl transferase D. DHFR Q5. A young female presented with left sided severe throbbing headache associated with nausea, vomiting, photophobia and phonophobia. Which of the following Q11. Drug inhibiting granulocyte migration is: drug can provide immediate relief to this patient? A. Montelukast B. Cromoglycate A. Propranolol B. Sumatriptan C. Colchicine D. Felbamate C. Topiramate D. Flunarizine Q12. Pegloticase is used for treatment of :- Q6. Drug of choice in paracetamol overdose is A. Ankylosing spondylosis A. N-acetylcysteine B. Dopamine B. CPPD C. Hydralazine D. Furosemide C. Chronic tophaceous gout Q7. A 34 week pregnant female with polyhydramnios D. Refractory Rheumatoid arthritis 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 Answers 1. - C 3. - A 5. - B 7. - B 9. - C 11. - C 2. - A 4. - A 6. - A 8. - D 10. - A 12. - C 28 Cerebellum Quick Revision Notes Q13. A patient diagnosed with Rheumatoid arthritis was A. IL-6 B. IL-12 on medications. After 2 years, he developed blurring C. IL-2 D. IL-3 of vision and was found to have corneal opacity. Which drug is most likely to cause this? Q15. A 40 year old male patient presents to hospital A. Sulfasalazine B. Chloroquine with pain in great toe. It was diagnosed to be a case of gout. Which of the following drug increases the C. Methotrexate D. Leflunomide excretion of uric acid in urine? Q14. Tocilizumab is an immunosuppressive drug used A. Colchicine B. Probenecid for Rheumatoid arthritis. It is a monoclonal antibody C. Allopurinol D. Febuxostat against Answers 13. - B 15. - B 14. - A  Chapter - 4 Diuretics Diuretics → Cause loss of Na+ & H2O in urine 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 Indapamide Methiazide Metolazone Polythiazide Classification Based On Site of Action 1. OSMOTIC DIURETICS Uses Hypertension (DOC)Q → Includes mannitol –– Metolazone is effective in renal failure unlike Uses: other thiazides Acute Congestive GlaucomaQ Recurrent renal calcium stones Cerebral edema Diabetes insipidus Contra-Indications: Osteoporosis Cerebral hemorrhage Recurrent renal calcium stones Pulmonary edema S/E of both Thiazides and Loop diuretics ↓ Na+ ↑ Glucose 2. CARBONIC ANHYDRASE INHIBITORS ↓K + ↑ Uric Acid ↓ Mg 2+ ↑ Lipids → Acts on Proximal tubule ↓H + → Include: Acetazolamide – Given orally or IV Note: Loop diuretics cause hypocalcemia whereas Brinzolamide thiazides leads to hypercalcemia Given as eye drops Dorzolamide 5. K+ SPARING DIURETICS → Act on collecting ducts Indications: (1) Aldosterone Receptor Antagonists Glaucoma (Angle closure glaucoma) –– Spironolactone Mountain Sickness [DOC]Q –– Epleronone 30 Cerebellum Quick Revision Notes (2) Epithelial Na+ channel Blockers P → Potassium sparing Diuretics –– Triamterene A → Amiloride S → Spironolactone → Cause Gynaecomastia –– Amiloride T → Triamterene These drugs cause E → Epleronone → Do not cause Gynaecomastia ↓ Na+ & H2O → Diuresis Uses: ↑ K+ → Hyperkalemia ↑ H+ → Metabolic AcidosisQ - DOC for Conn’s Syndrome - DOC for Edema in Cirrhosis - DOC for Resistant hypertension Previous Years Questions A. Intravenous digoxin B. Oxygen supplementation Q1. Which of the following drug is a carbonic anhydrase inhibitor? C. Immediate descent A. Acetazolamide B. Hydrochlorthiazide D. Acetazolamide C. Furosemide D. Mannitol Q6. Mannitol is used in the management of: Q2. A 25 year old male presented to emergency with A. Congestive Cardiac Failure head trauma due to road traffic accident. In hospital, B. Acute Congestive Glaucoma the patient developed seizures. Emergency CT scan revealed widespread cerebral edema. Which of the C. Acute Renal Failure following is diuretic of choice for cerebral edema in D. Pulmonary edema this patient? A. Mannitol B. Spironolactone Q7. A patient of chronic liver cirrhosis presents with ascites. Which of the following is the best diuretic to C. Furosemide D. Hydrochlorthiazide be used in this patient? Q3. A 28 year old male went to Ladakh. He developed A. Eplerenone B. Chlorthiazide shortness of breath. Which of the following drug will C. Furosemide D. Triamterene you use for the treatment of mountain sickness at high altitude? Q8. Which of the following diuretic acts on the site X A. Acetazolamide B. Furosemide shown in the figure? C. Epleronone D. Salbutamol A. Furosemide B. Hydrochlorthizide C. Spironolactone D. Acetazolamide 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 Answers 1. - A 3. - A 5. - A 7. - A 2. - A 4. - A 6. - B 8. - B  Chapter - 5 Cardiovascular System CONGESTIVE HEART FAILURE 1. ↓ Work → Vasodilators In low output CHF, heart is not able to pump enough Venodilators A r t e r i o l a r Veno + Arteriolar blood. It results in accumulation of fluid in various parts dilators Dilators of body. ↓ Preload ↓ Afterload ↓ Preload and ↓ ACUTE (DECOMPENSATED) CHF Afterload Aim of treatment of Acute CHF Nitrates Hydralazine Na Nitroprusside 1. ↓ FLUID → Loop Diuretics ACE inhibitors Angiotensin receptor 2. ↑ PUMPING → Inotropics blockers A. b1 Agonists 2. ↓ Fluid → Loop Diuretics Dopamine 3. ↓ LVH [Cardiac Remodeling] Dobutamine It results due to excessive aldosterone 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 → These drugs decrease mortality in CHFQ Digoxin A. Beta Blockers B. ACE inhibitors C. Angiotensin Receptor Blockers D. Aldosterone Antagonists 32 Cerebellum Quick Revision Notes 4.  Contractility (Ionotropics) Drugs for Angina Pectoris DIGOXIN I. Nitrates → Only inotropic drug that can be given Orally II. Calcium Channel Blockers MOA in CHF III. Beta Blockers → Inhibit Na+- K+ pump that ↑ intracellular calcium IV. Potassium Channel Openers and thus inotropic action. MOA in Atrial Fibrillation I. Nitrates → Vagomimetic effect lead to ↓ AV conduction Q Mechanism of action: Adverse Effects Nitrates 1. Nausea, Vomiting [MC] ↓ 2. Arrhythmias Nitric oxide MC arrhythmia → Ventricular bigeminyQ ↓ Most specific → NPAT with AV BlockQ Guanylate cyclase 3. Xanthopsia / Yellow VisionQ ↓ 4. Gynaecomastia ↑ cGMP Drugs Causing Gynaecomastia ↓ DI : DIgoxin Vasodilation (Veins >> Arteries) S : Spironolacton