BP501T Medicinal Chemistry II — GPAT Question Bank

Unit	Topic	MCQ range
I	Antihypertensive, Antianginal, Vasodilator drugs	Q1 – Q20
II	Diuretics, Antiarrhythmic, Cardiotonics	Q21 – Q40
III	Anticoagulants, Antiplatelets, Antihyperlipidaemic, Antihistamines	Q41 – Q60
IV	Hypoglycaemic, Antithyroid, Sulphonamide, Quinolones	Q61 – Q80
V	Antitubercular, Antifungal, Antiviral, Antineoplastic, Diagnostic, Anti-leprosy, Antigout	Q81 – Q100

1

Captopril is chemically: GPAT 2019

A1-[(2S)-3-hydroxy-2-methylpropanoyl]-L-proline
B1-[(2S)-3-mercapto-2-methylpropanoyl]-L-proline
C1-[(2S)-3-mercapto-2-methylpropanoyl]-L-alanine
D1-[(2S)-2-amino-3-mercaptopropanoyl]-L-proline

📘 Explanation

✔ Correct — B: Captopril's IUPAC name is 1-[(2S)-3-mercapto-2-methylpropanoyl]-L-proline. Three essentials: (i) L-proline ring (Zn²⁺-binding pocket of ACE), (ii) -SH (mercapto) that chelates the catalytic zinc, (iii) 2-methylpropanoyl bridge that mimics Phe-Ala of angiotensin-I. Molecular formula C₉H₁₅NO₃S.

✘ A wrong: "3-hydroxy" replaces SH with OH; loses zinc-chelating activity (OH binds much weaker than thiolate).

✘ C wrong: Replaces proline with L-alanine — loses the rigid pyrrolidine ring that fits ACE's S1′ subsite; activity drops ~ 100 fold.

✘ D wrong: Adds an α-amino group which introduces an additional charge and destroys the dipeptide-mimetic geometry.

2

Which enzyme is inhibited by captopril? GPAT 2019

ARenin
BAngiotensinogen
CAngiotensin-convertin
DChymase

📘 Explanation

✔ Correct — C: Captopril is a selective inhibitor of ACE (dipeptidyl carboxypeptidase). ACE converts angiotensin-I (decapeptide) to angiotensin-II (octapeptide). Blocking it reduces Ang-II → vasodilation + ↓ aldosterone + ↑ bradykinin (causes the dry cough ADR).

✘ A wrong: Renin cleaves angiotensinogen to Ang-I; captopril does not bind renin. Aliskiren is a renin inhibitor.

✘ B wrong: Angiotensinogen is a substrate, not an enzyme.

✘ D wrong: Chymase is an alternative Ang-II generating enzyme in heart; not a primary target of captopril.

3

Which of the following ACE inhibitors is a prodrug? Most Probable

AEnalapril
BCaptopril
CLisinopril
DAliskiren

📘 Explanation

✔ Correct — A: Enalapril is an ethyl ester prodrug; hepatic esterases hydrolyse it to the active diacid enalaprilat. Rationale: the parent diacid is poorly absorbed orally — esterification improves bioavailability. Similar prodrugs: ramipril, benazepril, fosinopril, trandolapril, quinapril, moexipril, perindopril (all "-pril" except captopril and lisinopril).

✘ B wrong: Captopril is an active drug (not a prodrug) — contains free -SH.

✘ C wrong: Lisinopril is an active drug (L-lysine analogue), not a prodrug — directly absorbed as active carboxylate.

✘ D wrong: Aliskiren is a direct renin inhibitor (not a prodrug, not an ACE inhibitor).

4

Losartan belongs to which class? GPAT 2019

AACE inhibitor
Bβ-adrenergic blocker
CAngiotensin-II
DCalcium channel blocker

📘 Explanation

✔ Correct — C: Losartan is the prototype biphenyl-tetrazole ARB — binds AT1 receptor and blocks Ang-II effects without affecting bradykinin (hence no cough). Metabolised by CYP2C9 to the active metabolite EXP3174 which is more potent.

✘ A wrong: ACE inhibitors end in "-pril"; losartan does not block ACE.

✘ B wrong: β-blockers end in "-olol" (atenolol, metoprolol).

✘ D wrong: Calcium channel blockers are dihydropyridines (-dipines) or non-DHP (verapamil, diltiazem).

5

The tetrazole ring in losartan is a bioisostere of: GPAT 2019

AAmino (–NH₂) group
BCarboxylic acid (–COOH) group
CSulfonamide (–SO₂NH₂) group
DHydroxyl (–OH) group

📘 Explanation

✔ Correct — B: The 1H-tetrazole ring has pKa ≈ 4.5–4.9, similar to carboxylic acid (pKa ≈ 4.2), and is planar/acidic/H-bond donor — making it a classic non-classical bioisostere of –COOH. Advantage: ~ 10× better membrane permeability (lipophilic), metabolically stable (not decarboxylated), and provides stronger receptor binding in losartan, valsartan, candesartan, irbesartan.

✘ A wrong: –NH₂ is basic (pKa ~ 10.5); opposite of acidic tetrazole.

✘ C wrong: Sulfonamide (–SO₂NH₂, pKa ~ 10-11) is a weaker acid and not the commonly recognised bioisostere of COOH; it is used elsewhere (celecoxib).

✘ D wrong: –OH is essentially neutral (pKa ~ 16), no acidic proton at physiological pH.

6

Propranolol is: GPAT 2019

ACardioselective β1 blocker
BSelective α1 blocker
CPartial β-agonist
DNon-selective β-blocker

📘 Explanation

✔ Correct — D: Propranolol (the first β-blocker, J.W. Black, Nobel 1988) is a non-selective β-blocker — equally blocks β1 (heart) & β2 (bronchi, smooth muscle). Hence asthma is a contraindication (β2 blockade causes bronchospasm). Aryloxypropanolamine pharmacophore.

✘ A wrong: Cardioselective β1 blockers are atenolol, metoprolol, bisoprolol, nebivolol.

✘ B wrong: α1 blockers are prazosin, terazosin, doxazosin ("-zosin").

✘ C wrong: Partial β-agonists (intrinsic sympathomimetic activity) are pindolol, acebutolol — but still β-blockers; not propranolol.

7

The pharmacophore of β-blockers (e.g. propranolol) is: GPAT 2019

AAryl-amino-propanol
BAryloxy-propanolamine
CAryl-piperidine
DBenzothiazepine

📘 Explanation

✔ Correct — B: Classical β-blockers share the aryloxy-propanolamine pharmacophore: aryl-O-CH₂-CH(OH)-CH₂-NH-R. The β-OH and NH mimic the β-OH and amino group of endogenous catecholamines; the bulky N-isopropyl / tert-butyl blocks β-receptor activation. S-(–) enantiomer is active.

✘ A wrong: Aryl-amino-propanol lacks the -O- ether linker (first-generation arylethanolamines — isoprenaline, sotalol); the ether bridge defines aryloxy-propanolamines.

✘ C wrong: Aryl-piperidine is found in other classes (e.g. fentanyl-type opioids, haloperidol).

✘ D wrong: Benzothiazepine is the diltiazem scaffold (Ca-channel blocker), not a β-blocker.

8

Atenolol differs from propranolol in being: GPAT 2019

Aβ1-selective and hydrophilic
BNon-selective but lipophilic
Cα and β blocker
DPartial β agonist

📘 Explanation

✔ Correct — A: Atenolol is a β1-selective (cardioselective), hydrophilic β-blocker (log P = 0.16). Low BBB penetration → minimal CNS ADR (nightmares, depression). Renally eliminated; longer t½ ~ 6 h → once-daily. Polar para-acetamido substitution accounts for hydrophilicity.

✘ B wrong: Propranolol itself is the non-selective, lipophilic prototype; atenolol is the opposite.

✘ C wrong: α+β blockers are labetalol, carvedilol (have added α1 activity).

✘ D wrong: ISA agents are pindolol, acebutolol — atenolol has no ISA.

9

Nifedipine is synthesised by: Most Probable

AHoffmann rearrangement
BMannich reaction
CHantzsch dihydropyridine
DGould-Jacobs reaction

📘 Explanation

✔ Correct — C: Nifedipine (1,4-dihydropyridine Ca-channel blocker) is made by Hantzsch dihydropyridine synthesis: 2-nitrobenzaldehyde + 2 equivalents of methyl acetoacetate + NH₃ (or NH₄OAc) → 1,4-dihydropyridine in one pot. Other DHPs (amlodipine, felodipine, nicardipine, isradipine) follow the same route.

✘ A wrong: Hoffmann rearrangement converts amides to amines with one-carbon loss — not relevant to DHP synthesis.

✘ B wrong: Mannich reaction is a 3-component amine-aldehyde-active methylene; yields β-amino ketones; used in tramadol synthesis.

✘ D wrong: Gould-Jacobs reaction builds 4-quinolone cores from anilines + ethyl ethoxymethylenemalonate → used for fluoroquinolone synthesis, not DHPs.

10

Verapamil is a: Most Probable

ADihydropyridine Ca channel blocker
Bβ-blocker
CBenzothiazepine Ca channel blocker
DPhenylalkylamine Ca channel blocker

📘 Explanation

✔ Correct — D: Verapamil is a phenylalkylamine CCB (papaverine-derived). It is cardio-selective (acts on AV/SA node) → used for SVT, atrial fibrillation rate control, angina, hypertension. Slows AV conduction & has negative inotropic effect.

✘ A wrong: DHPs are vasoselective (amlodipine, nifedipine, felodipine) — don't affect heart much.

✘ B wrong: Verapamil is NOT a β-blocker; do not combine with β-blocker (heart block risk).

✘ C wrong: Benzothiazepine is diltiazem's scaffold — intermediate selectivity.

11

Nitroglycerin (GTN) relaxes vascular smooth muscle by: Most Probable

AReleasing nitric oxide → ↑ cGMP
BBlocking β-receptors
CInhibiting PDE-5
DOpening ATP-sensitive K+ channels

📘 Explanation

✔ Correct — A: Nitroglycerin is enzymatically (by mitochondrial ALDH-2) denitrated to release NO; NO activates soluble guanylyl cyclase → ↑ cGMP → activates protein kinase G → dephosphorylates myosin light chain → vasodilation (predominantly venous at low dose). Classic antianginal mechanism.

✘ B wrong: β-blockade is not nitroglycerin's mechanism.

✘ C wrong: PDE-5 inhibitors (sildenafil) indirectly raise cGMP by preventing its breakdown; not the action of GTN.

✘ D wrong: K-ATP channel openers are minoxidil, nicorandil (nicorandil also is an NO donor, but GTN primary mechanism is via NO release).

12

Which ACE inhibitor has the longest duration of action? GPAT 2019

ACaptopril
BRamipril
CEnalapril
DLisinopril

📘 Explanation

✔ Correct — B: Ramipril (via active metabolite ramiprilat) has t½ ≈ 13–17 h, longest among listed; once-daily dosing. Its indanecarboxyl chain provides high tissue ACE binding & proven mortality benefit in HOPE trial.

✘ A wrong: Captopril has short t½ (~ 2 h) and is usually dosed TID (BID with SR).

✘ C wrong: Enalaprilat t½ ~ 11 h — once or twice daily; shorter than ramiprilat.

✘ D wrong: Lisinopril t½ ~ 12 h — once daily but slightly shorter than ramipril.

13

Which of the following is a dihydropyridine CCB that is a prodrug of a better known DHP? Most Probable

AAmlodipine
BNifedipine
CClevidipine
DNicardipine

📘 Explanation

✔ Correct — C: Clevidipine is a butyrate ester prodrug given IV for acute severe hypertension; it is hydrolysed by blood and tissue esterases (t½ ~ 1 min) → very rapid onset & offset, ideal for titration in ICU. (Note: the choice of a "prodrug DHP" is mostly clevidipine among common DHPs.)

✘ A wrong: Amlodipine is an active drug with long t½ (30-50 h) due to slow dissociation from the receptor — not a prodrug.

✘ B wrong: Nifedipine is the first DHP, fully active as parent.

✘ D wrong: Nicardipine is active as parent, not a prodrug.

14

Central α2-agonist used in hypertension, especially in pregnancy: Most Probable

AMethyldopa
BPrazosin
CPropranolol
DHydralazine

📘 Explanation

✔ Correct — A: Methyldopa is decarboxylated → α-methyl-noradrenaline → activates central α2-receptors in medulla → ↓ sympathetic outflow → ↓ BP. Safe in pregnancy (long safety record, WHO recommended).

✘ B wrong: Prazosin is a peripheral α1 antagonist, not central α2 agonist.

✘ C wrong: Propranolol is a β-blocker (not used for HTN in pregnancy usually; β-blockers except labetalol have some issues).

✘ D wrong: Hydralazine is a direct vasodilator (also used in severe HTN in pregnancy — but mechanism is NOT central α2 agonism).

15

Which of the following is a potassium channel opener used in refractory hypertension and also causes hypertrichosis? Most Probable

ADiazoxide
BMinoxidil
CSodium nitroprusside
DHydralazine

📘 Explanation

✔ Correct — B: Minoxidil (via active metabolite minoxidil-sulphate) opens ATP-sensitive K⁺ channels on vascular smooth muscle → hyperpolarisation → vasodilation. Potent arteriolar dilator for refractory HTN. Famous ADR: hypertrichosis — exploited topically (Rogaine®) for androgenic alopecia.

✘ A wrong: Diazoxide is also a K-ATP opener, used for hypertensive emergencies & insulinoma — but doesn't cause the hair growth effect as characteristically as minoxidil.

✘ C wrong: Sodium nitroprusside releases NO — IV use only in hypertensive crisis; does NOT open K channels.

✘ D wrong: Hydralazine is a direct vasodilator, likely opens K channels too but not via K-ATP channels and does not cause hypertrichosis.

16

Sodium nitroprusside in hypertensive emergency acts by releasing: Most Probable

ACarbon monoxide (CO)
BHydrogen sulphide
COzone
DNitric oxide (NO) and cyanide

📘 Explanation

✔ Correct — D: SNP (Na₂[Fe(CN)₅NO]·2H₂O) releases NO (vasodilator) and 5 cyanide ions per molecule. NO causes arterial + venous dilation; cyanide is detoxified by rhodanese (needs thiosulfate) → thiocyanate renally excreted. Prolonged infusion → cyanide / thiocyanate toxicity; give sodium thiosulfate + hydroxocobalamin.

✘ A wrong: CO-releasing molecules exist but SNP doesn't release CO.

✘ B wrong: H₂S is an endogenous signalling molecule but SNP does not release it.

✘ C wrong: Ozone has no role in cardiovascular pharmacology.

17

β-blocker that is also an α1-blocker and used in hypertension + heart failure: GPAT 2019

AAtenolol
BCarvedilol
CBisoprolol
DNebivolol

📘 Explanation

✔ Correct — B: Carvedilol is a non-selective β-blocker + α1-blocker + antioxidant. First-line for CHF along with bisoprolol & metoprolol succinate (all reduce mortality in HFrEF). Labetalol is the other α+β combined blocker (used in severe HTN, pheochromocytoma, pregnancy HTN).

✘ A wrong: Atenolol is β1-selective; no α activity.

✘ C wrong: Bisoprolol is β1-selective (and used for CHF, but no α activity).

✘ D wrong: Nebivolol is β1-selective + NO-releasing → vasodilation; not an α-blocker.

18

Which statement about clonidine is correct? Most Probable

ACentral α2-agonist
BPeripheral α1-blocker; first-dose syncope
CGanglion blocker
DAngiotensin receptor blocker

📘 Explanation

✔ Correct — A: Clonidine is an imidazoline → central α2 and imidazoline-I1 agonist → ↓ sympathetic outflow → ↓ BP. Sudden withdrawal causes rebound hypertension; taper slowly or overlap with β-blocker. Also used in ADHD, opioid withdrawal, menopausal hot flushes.

✘ B wrong: Prazosin causes first-dose syncope (α1 blocker).

✘ C wrong: Ganglion blockers (hexamethonium, trimethaphan) are obsolete.

✘ D wrong: ARBs end in "-sartan" — unrelated to clonidine.

19

Which compound is a specific renin inhibitor? Most Probable

ALosartan
BEnalaprilat
CValsartan
DAliskiren

📘 Explanation

✔ Correct — D: Aliskiren is the first orally active direct renin inhibitor (FDA 2007). Blocks the conversion of angiotensinogen → Ang-I at the top of the RAAS cascade. Low oral bioavailability (~ 2.5 %) but long t½ (24-40 h). Contraindicated in combination with ACEI/ARB in diabetics (hyperkalaemia, AKI — ALTITUDE trial).

✘ A wrong: Losartan is an ARB.

✘ B wrong: Enalaprilat is active form of ACE inhibitor.

✘ C wrong: Valsartan is an ARB.

20

The "–dipine" suffix pharmacologically denotes: Practice Question

AACE inhibitor
Bα-blocker
CDihydropyridine
DARB

📘 Explanation

✔ Correct — C: The INN suffix "-dipine" indicates a 1,4-dihydropyridine Ca-channel blocker: amlodipine, nifedipine, felodipine, isradipine, nicardipine, lacidipine, nimodipine, lercanidipine, clevidipine, levamlodipine. All vasoselective except nimodipine (cerebroselective — used in SAH).

✘ A wrong: ACEI suffix is "-pril" (captopril, enalapril, ramipril).

✘ B wrong: α1-blocker suffix is "-zosin" (prazosin, terazosin, doxazosin, tamsulosin).

✘ D wrong: ARB suffix is "-sartan" (losartan, valsartan, telmisartan, irbesartan).

21

Carbonic anhydrase inhibitor used as diuretic and in glaucoma: Most Probable

AHydrochlorothiazide
BAcetazolamide
CFurosemide
DSpironolactone

📘 Explanation

✔ Correct — B: Acetazolamide (sulphonamide) inhibits CA in PCT → ↓ H⁺-Na⁺ exchange → ↑ NaHCO₃ excretion → alkaline diuresis. Clinical uses: glaucoma (↓ aqueous humor), altitude sickness prophylaxis, metabolic alkalosis, familial periodic paralysis, urinary alkalinisation.

✘ A wrong: HCTZ is a thiazide — acts at DCT on Na-Cl symporter.

✘ C wrong: Furosemide blocks Na-K-2Cl symporter at thick ascending limb; not CA.

✘ D wrong: Spironolactone is an aldosterone antagonist at collecting duct.

22

Furosemide acts on: GPAT 2020

AProximal convoluted tubule
BDistal convoluted tubule
CThick ascending limb of loop
DCollecting duct

📘 Explanation

✔ Correct — C: Furosemide (and all loop diuretics — bumetanide, torsemide, ethacrynic acid) block the Na⁺-K⁺-2Cl⁻ symporter (NKCC2) at the thick ascending limb → 25 % of filtered Na⁺ excreted (most potent diuretic). Uses: CHF with pulmonary oedema, acute kidney injury, hypercalcaemia, ↑ K⁺.

✘ A wrong: PCT is where CA inhibitors (acetazolamide) and osmotic diuretics (mannitol) act.

✘ B wrong: DCT is the site of thiazides (Na-Cl symporter).

✘ D wrong: Collecting duct is where K⁺-sparing (spironolactone, amiloride) and ADH (vasopressin) act.

23

Chemical class of hydrochlorothiazide: GPAT 2021

ABenzothiadiazine sulphonamide
BPteridine
CPyrazinoyl guanidine
DSpirolactone

📘 Explanation

✔ Correct — A: HCTZ is a benzothiadiazine-1,1-dioxide fused with a sulphonamide (–SO₂NH₂) — the sulphonyl group is essential for diuretic activity. SAR: 3,4-dihydro confers 10× activity over parent; chloro at C6 mandatory; sulphamoyl at C7 mandatory.

✘ B wrong: Pteridine is the scaffold of triamterene (K-sparing).

✘ C wrong: Pyrazinoyl guanidine is amiloride's structure.

✘ D wrong: Spirolactone structure = spironolactone (K-sparing, aldosterone antagonist).

24

Spironolactone acts by antagonising: GPAT 2015

AADH (vasopressin) receptor
BAngiotensin-II receptor
CGlucocorticoid receptor
DAldosterone

📘 Explanation

✔ Correct — D: Spironolactone is a steroidal aldosterone antagonist — blocks the mineralocorticoid receptor in cortical collecting tubule → ↓ Na⁺ reabsorption + ↓ K⁺ secretion (K-sparing). Uses: CHF (mortality benefit — RALES trial), primary hyperaldosteronism, ascites, PCOS, acne (anti-androgen activity). Eplerenone is a more selective newer analogue.

✘ A wrong: ADH antagonists are "vaptans" (tolvaptan, conivaptan) — used in SIADH, hyponatraemia.

✘ B wrong: AT1 blockers are sartans (losartan, valsartan).

✘ C wrong: Glucocorticoid receptor is target of corticosteroids (prednisolone) and antagonist mifepristone.

25

Mannitol is a: GPAT 2020

AThiazide diuretic
BOsmotic diuretic
CK-sparing diuretic
DCarbonic anhydrase inhibitor

📘 Explanation

✔ Correct — B: Mannitol (a sugar alcohol, D-mannose-derived) is a freely filtered non-reabsorbable osmotic agent → pulls water into tubular lumen → osmotic diuresis. Uses: ↓ intracranial pressure (cerebral oedema), ↓ intraocular pressure (acute glaucoma), forced diuresis in poisoning, AKI oliguria (controversial). Given IV only (oral causes osmotic diarrhoea).

✘ A wrong: Thiazides are benzothiadiazines (chemical class, not osmotic).

✘ C wrong: K-sparing = spironolactone, amiloride, triamterene.

✘ D wrong: CA inhibitors are acetazolamide, dorzolamide.

26

Amiloride works by: GPAT 2015

ABlocking aldosterone receptor
BBlocking Na-Cl symporter
CBlocking ENaC
DBlocking H+/K+ ATPase

📘 Explanation

✔ Correct — C: Amiloride (and triamterene) block the epithelial Na⁺ channel (ENaC) at the luminal side of principal cells in collecting duct. K-sparing but weak diuretic. Amiloride also inhibits Na/H exchanger. Used in combination with HCTZ/furosemide to offset K⁺ loss.

✘ A wrong: Aldosterone receptor blockade = spironolactone/eplerenone (steroidal class).

✘ B wrong: Na-Cl symporter = thiazides (DCT).

✘ D wrong: H+/K+ ATPase = proton pump inhibitors (omeprazole).

27

Vaughan-Williams Class I antiarrhythmics act by: Most Probable

ABlocking Na+ channels
BBlocking β receptors
CProlonging action potential (K channel block)
DBlocking Ca channels

📘 Explanation

✔ Correct — A: Vaughan-Williams classification: Class I = Na⁺ channel blockers (subclass: IA quinidine, procainamide, disopyramide; IB lidocaine, mexiletine, phenytoin; IC flecainide, propafenone). Class II = β-blockers. Class III = K⁺ blockers (amiodarone, sotalol, dofetilide, ibutilide). Class IV = Ca-channel blockers (verapamil, diltiazem).

✘ B wrong: β-receptor block = Class II.

✘ C wrong: K channel block = Class III.

✘ D wrong: Ca channel block = Class IV.

28

Drug of choice for acute ventricular arrhythmias during MI: Most Probable

AQuinidine
BLidocaine IV
CFlecainide
DDigoxin

📘 Explanation

✔ Correct — B: Lidocaine IV (Class IB) preferentially blocks activated/inactivated Na⁺ channels of ischaemic myocardium → stabilises membrane in MI-related VT/VF without affecting normal tissue. Now amiodarone preferred; but lidocaine is still used especially post-MI VT.

✘ A wrong: Quinidine (Class IA) is largely obsolete due to pro-arrhythmia (TdP) & GI/immunological ADR.

✘ C wrong: Flecainide (Class IC) contraindicated in structural/ischaemic heart disease (CAST trial — increased mortality).

✘ D wrong: Digoxin used for AF rate control in CHF — not for ventricular arrhythmia.

29

Amiodarone is predominantly a Class ___ antiarrhythmic: GPAT 2025

AIII (K-channel blocker)
BI (Na-channel blocker)
CII (β-blocker)
DIV (Ca-channel blocker)

📘 Explanation

✔ Correct — A: Amiodarone is predominantly Class III (blocks K⁺ channels → prolongs action potential & QT), but also has Class I + II + IV activity (amiodarone = "all classes"). Iodine-rich benzofuran; t½ ≈ 30-100 days. ADR: pulmonary fibrosis, hypothyroidism/hyperthyroidism, corneal deposits, hepatitis, bluish skin.

✘ B wrong: Has I activity but predominant is III.

✘ C wrong: Has β-blocking activity but predominant is III.

✘ D wrong: Has Ca-blocking activity but predominant is III.

30

Digoxin exerts its positive inotropic effect by inhibiting: GPAT 2017

ACa²⁺-ATPase of SR
Bβ-adrenergic receptor
CNa⁺
DL-type Ca channel

📘 Explanation

✔ Correct — C: Digoxin binds the α-subunit of cardiac Na⁺/K⁺-ATPase → ↑ intracellular Na⁺ → reduces the driving force for Na-Ca exchanger (NCX) → ↑ intracellular Ca²⁺ → ↑ contractility. Also vagal activity ↑ → ↓ AV conduction (rate control in AF).

✘ A wrong: SERCA inhibition is seen with thapsigargin (research); not digoxin.

✘ B wrong: β-receptors are stimulated (not blocked) for positive inotropy by dobutamine / noradrenaline.

✘ D wrong: L-type Ca channel blockade would reduce inotropy (CCBs).

31

Cardiac glycoside digoxin is obtained from: GPAT 2017

ADigitalis lanata
BCatharanthus roseus
CStrophanthus kombe
DRauwolfia serpentina

📘 Explanation

✔ Correct — A: Digoxin is isolated from the leaves of Digitalis lanata (woolly foxglove). Digitoxin comes from both D. lanata & D. purpurea. Aglycone = digoxigenin (a steroid with cis A/B, trans B/C, cis C/D fused rings + γ-lactone); sugar = 3 × digitoxose.

✘ B wrong: Catharanthus roseus yields vinca alkaloids (vincristine, vinblastine).

✘ C wrong: Strophanthus kombe yields ouabain (K-strophanthin) — another cardiac glycoside but not digoxin.

✘ D wrong: Rauwolfia serpentina yields reserpine (antihypertensive, antipsychotic).

32

Digibind (DigiFab) is used as antidote for digoxin toxicity. It consists of: GPAT 2017

AAtropine injection
BOvine
CPhysostigmine
DCalcium gluconate

📘 Explanation

✔ Correct — B: DigiFab contains Fab fragments from sheep immunised with digoxin; binds free digoxin → renally excreted. Used for: life-threatening arrhythmia due to digoxin toxicity, K⁺ > 5 mEq/L with digoxin overdose, > 10 mg adult acute ingestion.

✘ A wrong: Atropine treats bradycardia (symptomatic) but doesn't remove digoxin.

✘ C wrong: Physostigmine is an AChE inhibitor, used for anticholinergic toxicity.

✘ D wrong: Calcium gluconate is contraindicated in digoxin toxicity ("stone heart" — may worsen arrhythmia).

33

Drug of choice for rate control in atrial fibrillation when β-blockers contraindicated: Practice Question

AFlecainide
BQuinidine
CLidocaine
DVerapamil or diltiazem

📘 Explanation

✔ Correct — D: Non-DHP Ca-channel blockers (verapamil, diltiazem) slow AV conduction → rate control in AF. Alternative to β-blockers. Digoxin is also an option especially in CHF patients.

✘ A wrong: Flecainide is used for rhythm control (pharmacological cardioversion) not rate control; contraindicated in structural heart disease.

✘ B wrong: Quinidine for rhythm conversion only; pro-arrhythmic.

✘ C wrong: Lidocaine for ventricular arrhythmia, not atrial.

34

Thiazide diuretics cause all of the following EXCEPT: GPAT 2021

AHyperuricaemia
BHyperglycaemia and dyslipidaemia
CHypomagnesaemia
DHyperkalaemia

📘 Explanation

✔ Correct — D: Thiazides cause HYPOkalaemia, NOT hyperkalaemia. The memorable mnemonic — "hyper GLUC" — hyperGlycaemia, hyperLipidaemia, hyperUricaemia, hyperCalcaemia; plus hypoKalaemia, hypoNatraemia, hypoMagnesaemia. So "hyperkalaemia" is the exception.

✘ A wrong — but is correct statement: Hyperuricaemia, hypercalcaemia, hypokalaemia ARE thiazide effects — but question asks "EXCEPT".

✘ B wrong — but is correct statement: Hyperglycaemia, dyslipidaemia ARE thiazide effects.

✘ C wrong — but is correct statement: Hypomagnesaemia IS a thiazide effect.

35

Which antiarrhythmic drug is most likely to cause lupus-like syndrome? Most Probable

AAmiodarone
BQuinidine
CProcainamide
DLidocaine

📘 Explanation

✔ Correct — C: Procainamide (Class IA) is the classic cause of drug-induced lupus (DIL) — positive anti-histone antibodies; slow acetylators at higher risk. Other drugs causing DIL — hydralazine, isoniazid, chlorpromazine, minocycline.

✘ A wrong: Amiodarone's major ADR are pulmonary fibrosis, thyroid dysfunction, corneal deposits — not lupus.

✘ B wrong: Quinidine causes cinchonism (tinnitus, headache), thrombocytopenia, GI — not lupus primarily.

✘ D wrong: Lidocaine at high dose → CNS toxicity, seizures; not lupus.

36

Diltiazem is chemically a: Most Probable

ADihydropyridine
BBenzothiazepine
CPhenylalkylamine
DAryloxypropanolamine

📘 Explanation

✔ Correct — B: Diltiazem has a 1,5-benzothiazepine core — third distinct class of CCB alongside DHPs (nifedipine) and phenylalkylamines (verapamil). Intermediate selectivity (acts on both heart and vessels). Used for angina, HTN, rate control in AF.

✘ A wrong: DHP = nifedipine, amlodipine.

✘ C wrong: Phenylalkylamine = verapamil.

✘ D wrong: Aryloxypropanolamine = β-blockers.

37

Adenosine is used in: Most Probable

AVentricular tachycardia
BParoxysmal supraventricular
CAtrial fibrillation rate control
DBradycardia

📘 Explanation

✔ Correct — B: Adenosine (6 mg IV rapid push, then 12 mg) activates A1 receptors in AV node → transient (~ 10 s) AV block → terminates re-entry in PSVT/AVNRT. Very short t½ (~ 10 s, degraded by deaminase). Contraindication: asthma (bronchospasm).

✘ A wrong: Adenosine doesn't terminate VT (wide-complex).

✘ C wrong: AF rate control = β-blocker, non-DHP CCB, digoxin; not adenosine.

✘ D wrong: Adenosine CAUSES bradycardia/asystole, doesn't treat it.

38

Which drug acts by selectively inhibiting the funny current (If) in the SA node? Most Probable

ARanolazine
BSacubitril
CIvabradine
DDronedarone

📘 Explanation

✔ Correct — C: Ivabradine selectively blocks HCN channels (funny current If) in SA node → lowers heart rate without negative inotropy or affecting BP. Used in chronic stable angina + HFrEF with HR > 70 bpm (on max β-blocker). Visual ADR: phosphenes (luminous light halos).

✘ A wrong: Ranolazine blocks late Na⁺ current for chronic angina.

✘ B wrong: Sacubitril is a neprilysin inhibitor (combined with valsartan = ARNi).

✘ D wrong: Dronedarone is an amiodarone analogue (no iodine; for AF).

39

Furosemide structure contains: GPAT 2020

AAnthranilic acid
BThiadiazine ring
CSpirolactone moiety
DPteridine nucleus

📘 Explanation

✔ Correct — A: Furosemide is a sulphamoyl-anthranilic acid derivative: 4-chloro-2-(furan-2-ylmethylamino)-5-sulphamoylbenzoic acid. Three critical features: -COOH (anthranilic acid), -SO₂NH₂ (sulphamoyl), furfurylamine side chain. Bumetanide is similar but has phenoxy group.

✘ B wrong: Thiadiazine = thiazide core.

✘ C wrong: Spirolactone = spironolactone.

✘ D wrong: Pteridine = triamterene.

40

Which cardiac drug has the longest half-life (30-100 days)? Practice Question

ADigoxin
BPropranolol
CAmiodarone
DLosartan

📘 Explanation

✔ Correct — C: Amiodarone has t½ 30–100 days due to lipid solubility and deposition in adipose, muscle, liver, lung. Steady state takes months; effects persist long after discontinuation. Loading dose always needed. Also explains persistent toxicity (pulmonary, thyroid, skin, corneal deposits) even after stopping.

✘ A wrong: Digoxin t½ ~ 36-40 h (normal renal function).

✘ B wrong: Propranolol t½ 3-6 h.

✘ D wrong: Losartan t½ 2 h; active metabolite EXP3174 t½ 6-9 h.

41

Warfarin acts by inhibiting: Most Probable

AAntithrombin III
BVitamin K epoxide
CThrombin directly
DFactor Xa directly

📘 Explanation

✔ Correct — B: Warfarin inhibits VKORC1, blocking the reduction of vitamin K epoxide → vitamin K hydroquinone; without active vitamin K, γ-carboxylation of glutamate residues on clotting factors II, VII, IX, X + proteins C/S fails → inactive factors. Onset 36-72 h (pre-formed factors must deplete). Narrow TI; INR 2-3.

✘ A wrong: Heparin activates antithrombin-III.

✘ C wrong: Direct thrombin inhibitors = dabigatran, argatroban, bivalirudin.

✘ D wrong: Direct Xa inhibitors = rivaroxaban, apixaban, edoxaban.

42

Warfarin is chemically a: Most Probable

A4-hydroxycoumarin derivative
BIndandione
CSulphated glycosaminoglycan
DPyranoindole

📘 Explanation

✔ Correct — A: Warfarin is 4-hydroxycoumarin with 3-(α-acetonylbenzyl) substituent. Derived from dicoumarol (found in spoiled sweet clover silage that caused cattle haemorrhages). Sodium salt is water-soluble. R/S enantiomers both active; S form 3-5× more potent, metabolised by CYP2C9.

✘ B wrong: Indandione derivatives = phenindione, anisindione (largely obsolete).

✘ C wrong: Sulphated glycosaminoglycan = heparin.

✘ D wrong: Pyranoindole scaffold is not relevant to warfarin.

43

Heparin's primary anticoagulant mechanism: Most Probable

ADirect inhibition of thrombin
BVitamin K antagonism
CBinding antithrombin-III
DDirect inhibition of factor Xa

📘 Explanation

✔ Correct — C: Heparin binds the lysine residues of antithrombin-III via its unique pentasaccharide sequence → AT-III undergoes conformational change → 1000× acceleration of inactivation of thrombin (IIa) and factor Xa. LMWH (enoxaparin) = preferential anti-Xa activity. Monitor with aPTT (UFH); LMWH with anti-Xa levels.

✘ A wrong: Heparin is INDIRECT thrombin inhibitor (via AT-III).

✘ B wrong: Vitamin K antagonism = warfarin.

✘ D wrong: Direct Xa inhibitors are rivaroxaban, apixaban.

44

Antidote for heparin overdose: Most Probable

AVitamin K
BProtamine sulphate
CFresh frozen plasma
DActivated charcoal

📘 Explanation

✔ Correct — B: Protamine sulphate is a strongly basic protein from salmon sperm; electrostatically binds acidic heparin (1 mg neutralises ~ 100 units UFH). Only partially reverses LMWH (≈ 60 %). Does NOT reverse fondaparinux.

✘ A wrong: Vitamin K reverses warfarin.

✘ C wrong: FFP provides clotting factors — helps warfarin reversal (alongside vit K or PCC).

✘ D wrong: Activated charcoal adsorbs orally ingested drugs; heparin is IV.

45

Atorvastatin mechanism of action: Most Probable

ABlock cholesterol absorption at NPC1L1
BActivate PPAR-α
CInhibit HMG-CoA reductase → ↓ cholesterol
DInhibit PCSK9 protein

📘 Explanation

✔ Correct — C: Atorvastatin (and all statins — ending "-statin") is a competitive HMG-CoA reductase inhibitor. Mimics HMG-CoA structurally; reduces mevalonate formation → hepatic cholesterol ↓ → compensatory ↑ LDL-R on hepatocytes → ↑ clearance of circulating LDL. Lowers LDL by 30-60 %. Pleiotropic effects (↓ inflammation, plaque stabilisation).

✘ A wrong: NPC1L1 inhibition = ezetimibe.

✘ B wrong: PPAR-α activation = fibrates (fenofibrate, gemfibrozil).

✘ D wrong: PCSK9 inhibition = alirocumab, evolocumab (mAbs); inclisiran (siRNA).

46

Which drug lowers LDL by blocking intestinal cholesterol absorption at NPC1L1? Most Probable

AGemfibrozil
BCholestyramine
CNiacin
DEzetimibe

📘 Explanation

✔ Correct — D: Ezetimibe selectively inhibits the Niemann-Pick C1-Like 1 (NPC1L1) transporter at the brush border of enterocytes → blocks cholesterol absorption (~ 50 %). LDL reduction 15-20 %. Often combined with statin (Vytorin = ezetimibe + simvastatin) — IMPROVE-IT trial showed added benefit.

✘ A wrong: Gemfibrozil is a PPAR-α agonist (fibrate) — lowers TG primarily.

✘ B wrong: Cholestyramine is a bile-acid binder (enteric resin); different mechanism.

✘ C wrong: Niacin (nicotinic acid) reduces VLDL synthesis in liver; causes flushing.

47

Fibric acid derivatives (fenofibrate, gemfibrozil) act through: Most Probable

AActivation of PPAR-α nuclear receptor
BInhibition of cholesteryl ester transfer protein
CInhibition of microsomal triglyceride transfer protein (MTP)
DInhibition of squalene epoxidase

📘 Explanation

✔ Correct — A: Fibrates are PPAR-α agonists → upregulate lipoprotein lipase (LPL) and apoA-I → ↓ triglycerides (by 30-50 %), modestly ↑ HDL. First line for high TG (> 500 mg/dL) to prevent pancreatitis.

✘ B wrong: CETP inhibitors (anacetrapib, evacetrapib) failed in large trials — not a mainstream class.

✘ C wrong: MTP inhibitors = lomitapide (for homozygous familial hypercholesterolaemia).

✘ D wrong: Squalene epoxidase is inhibited by terbinafine (antifungal).

48

Aspirin's antiplatelet effect is due to: Most Probable

AReversible COX-2 inhibition
BIrreversible acetylation of COX-1
CP2Y12 receptor blockade
DGPIIb/IIIa receptor blockade

📘 Explanation

✔ Correct — B: Aspirin irreversibly acetylates Serine-530 of platelet COX-1 → permanently blocks thromboxane A₂ synthesis for the platelet's lifetime (7-10 days, because platelets are anucleate and cannot regenerate COX-1). Low-dose (75-150 mg) exploits this for antiplatelet effect; higher doses also block endothelial COX (PGI₂) — less desirable.

✘ A wrong: COX-2 selective inhibitors are celecoxib, etoricoxib — used as analgesics, NOT antiplatelets.

✘ C wrong: P2Y12 blockade = clopidogrel, prasugrel, ticagrelor.

✘ D wrong: GPIIb/IIIa blockade = abciximab, eptifibatide, tirofiban.

49

Clopidogrel belongs to which class? Most Probable

ACOX inhibitor
BThrombin inhibitor
CADP P2Y12 receptor antagonist
DGPIIb/IIIa antagonist

📘 Explanation

✔ Correct — C: Clopidogrel is a thienopyridine prodrug — activated by CYP2C19 to the active thiol → irreversibly binds P2Y12 ADP receptor on platelets → blocks ADP-induced aggregation. Used post-MI, post-stent (with aspirin = dual antiplatelet). CYP2C19 poor metabolisers have reduced efficacy. Newer: ticagrelor (reversible, no genetic variability), prasugrel.

✘ A wrong: COX-1 inhibitor = aspirin.

✘ B wrong: Thrombin inhibitors = dabigatran, argatroban.

✘ D wrong: GPIIb/IIIa antagonists = abciximab etc.

50

Which IV antiplatelet drug is a monoclonal antibody fragment against GPIIb/IIIa? Most Probable

AEptifibatide
BTirofiban
CAbciximab
DTicagrelor

📘 Explanation

✔ Correct — C: Abciximab is a chimeric Fab fragment of a mouse-human antibody (7E3) directed against the platelet GPIIb/IIIa receptor; blocks fibrinogen binding → prevents aggregation. Used during PCI (percutaneous coronary intervention). IV only.

✘ A wrong: Eptifibatide is a small cyclic peptide GPIIb/IIIa antagonist (not an antibody).

✘ B wrong: Tirofiban is a non-peptide tyrosine-derived small molecule GPIIb/IIIa antagonist.

✘ D wrong: Ticagrelor is an oral P2Y12 antagonist (small molecule).

51

Cholestyramine lowers cholesterol by: Most Probable

ABinding bile acids in gut
BInhibiting HMG-CoA reductase
CBlocking NPC1L1 in enterocyte
DActivating LDL receptor gene

📘 Explanation

✔ Correct — A: Cholestyramine, colestipol, colesevelam are insoluble anion-exchange resins that sequester bile acids in the gut lumen → prevent enterohepatic recycling → liver uses more cholesterol to synthesise new bile acids → ↓ hepatic cholesterol → ↑ LDL-R → ↓ plasma LDL (15-30 %). ADR: constipation, drug absorption impairment (warfarin, digoxin, thiazide). Also used for pruritus of cholestasis, C. difficile diarrhoea.

✘ B wrong: HMG-CoA reductase inhibitors = statins.

✘ C wrong: NPC1L1 = ezetimibe.

✘ D wrong: LDL-R activation is an indirect result but NOT the direct mechanism of the resins.

52

Which antihistamine is NON-sedating (second-generation)? Most Probable

ADiphenhydramine
BCetirizine
CChlorpheniramine
DPromethazine

📘 Explanation

✔ Correct — B: Cetirizine (the carboxylic acid metabolite of hydroxyzine) is a 2nd-gen H1 antihistamine — polar → poor BBB crossing → non-sedating (levocetirizine is the active (R)-enantiomer). Other 2nd-gen: loratadine, fexofenadine, desloratadine, bilastine. Used for allergic rhinitis, urticaria.

✘ A wrong: Diphenhydramine (Benadryl) is 1st-gen — highly sedating.

✘ C wrong: Chlorpheniramine is 1st-gen (alkylamine) — sedating.

✘ D wrong: Promethazine (phenothiazine) is 1st-gen — strongly sedating (used for insomnia and antiemesis).

53

Chemical class of diphenhydramine: Most Probable

AEthanolamine
BAlkylamine
CPiperazine
DPhenothiazine

📘 Explanation

✔ Correct — A: 1st-generation H1 antihistamines by chemical class:
• Ethanolamine — diphenhydramine, dimenhydrinate, doxylamine, clemastine (strong sedative, antiemetic).
• Alkylamine — chlorpheniramine, brompheniramine (moderate sedation).
• Piperazine — hydroxyzine, meclizine, cyclizine (motion sickness).
• Phenothiazine — promethazine.
• Piperidine — cyproheptadine (appetite stimulant).
2nd-gen mostly piperidine/piperazine hybrids.

✘ B wrong: Alkylamine = chlorpheniramine, not diphenhydramine.

✘ C wrong: Piperazine = hydroxyzine, meclizine.

✘ D wrong: Phenothiazine = promethazine.

54

Which H1 antihistamine was withdrawn due to TdP (torsades de pointes) from CYP3A4 interactions? Most Probable

ALoratadine
BFexofenadine
CCetirizine
DTerfenadine

📘 Explanation

✔ Correct — D: Terfenadine was the first non-sedating H1; withdrawn (1997) after deaths from TdP caused by CYP3A4 inhibitors (erythromycin, ketoconazole, grapefruit) raising terfenadine levels → hERG K channel block → QT prolongation. Fexofenadine is its safe active carboxylic acid metabolite (no CYP metabolism). Similarly astemizole was withdrawn.

✘ A wrong: Loratadine is safe; no reported widespread QT issue.

✘ B wrong: Fexofenadine is the SAFE replacement.

✘ C wrong: Cetirizine is safe.

55

Which low-molecular-weight heparin (LMWH) is most prescribed? Practice Question

ADalteparin
BEnoxaparin
CTinzaparin
DNadroparin

📘 Explanation

✔ Correct — B: Enoxaparin (Clexane / Lovenox) is the most widely used LMWH globally. MW ~ 4500 Da; gives preferential anti-Xa:anti-IIa ratio ~ 3.8:1 compared to UFH's 1:1. Given SC; 1 mg/kg BID for VTE treatment, 40 mg OD for prophylaxis. No routine monitoring in normal renal function.

✘ A wrong: Dalteparin is second most used.

✘ C wrong: Tinzaparin is used in some countries.

✘ D wrong: Nadroparin is used mainly in Europe.

56

Dabigatran is a: Most Probable

AVitamin K antagonist
BDirect factor Xa inhibitor
CDirect thrombin inhibitor
DTissue plasminogen activator

📘 Explanation

✔ Correct — C: Dabigatran (prodrug etexilate) is an oral direct thrombin inhibitor — reversibly binds thrombin's active site. No INR monitoring. Used in non-valvular AF, DVT/PE. Specific antidote: idarucizumab (humanised Fab). Other DOACs (direct oral anticoagulants): rivaroxaban, apixaban, edoxaban (factor Xa inhibitors — antidote andexanet alfa).

✘ A wrong: Vitamin K antagonist = warfarin.

✘ B wrong: Direct Xa = rivaroxaban, apixaban, edoxaban.

✘ D wrong: tPA = alteplase, tenecteplase (fibrinolytic).

57

Niacin reduces plasma lipids by: Most Probable

AInhibiting lipolysis in adipocytes → reduced
BBlocking intestinal cholesterol absorption
CInhibiting HMG-CoA reductase
DActivating PPAR-α

📘 Explanation

✔ Correct — A: Nicotinic acid (niacin, vitamin B3) at pharmacological doses (1-3 g) activates the adipocyte GPR109A receptor → inhibits hormone-sensitive lipase → ↓ lipolysis → ↓ FFA delivery to liver → ↓ VLDL & LDL synthesis; also raises HDL (~ 15-35 %, best of any drug). ADR: flushing (prostaglandin-mediated; pre-dose aspirin helps), hyperuricaemia, hyperglycaemia, hepatotoxicity (IR > SR).

✘ B wrong: NPC1L1 blockade = ezetimibe.

✘ C wrong: HMG-CoA reductase = statins.

✘ D wrong: PPAR-α = fibrates.

58

Statin with the longest half-life (~ 19 h) and best intraday dosing flexibility: Practice Question

ASimvastatin
BAtorvastatin
CLovastatin
DPravastatin

📘 Explanation

✔ Correct — B: Atorvastatin has a long t½ (~ 14-19 h) and its active metabolites extend duration to ~ 20-30 h → can be given anytime of day, not just at night (unlike simvastatin & lovastatin which must be given at bedtime due to short t½ & peak cholesterol synthesis at night). Rosuvastatin has even longer t½ (~ 19 h).

✘ A wrong: Simvastatin t½ ~ 1.9 h; evening dose.

✘ C wrong: Lovastatin t½ ~ 2.9 h; evening dose.

✘ D wrong: Pravastatin t½ ~ 1.8 h.

59

Which H1-antagonist is also used for motion sickness because of its anticholinergic + antiemetic action? Most Probable

ALoratadine
BFexofenadine
CDimenhydrinate
DEbastine

📘 Explanation

✔ Correct — C: 1st-gen H1 antihistamines with additional anticholinergic action — dimenhydrinate, cyclizine, meclizine, promethazine — are used for motion sickness, vertigo, postoperative nausea & vomiting, hyperemesis gravidarum. They act on the vestibular system and vomiting centre.

✘ A wrong: Loratadine (2nd-gen) has minimal anticholinergic effect — not used for motion sickness.

✘ B wrong: Fexofenadine does not cross BBB — no CNS effects.

✘ D wrong: Ebastine is 2nd-gen; not used for motion sickness.

60

Streptokinase is a: Most Probable

APlasminogen activator
BAnticoagulant
CAntiplatelet
DAntibiotic

📘 Explanation

✔ Correct — A: Streptokinase is a protein from β-haemolytic streptococci that complexes with plasminogen → this complex activates other plasminogen → plasmin → dissolves fibrin (non-specific fibrinolysis). Used in STEMI (IV 1.5 million units over 60 min within 12 h). Pre-existing antistreptococcal antibodies may cause reactions; avoid repeat use within 12 months.

✘ B wrong: Anticoagulants prevent new clot; streptokinase dissolves existing clot.

✘ C wrong: Antiplatelets inhibit platelet function, not dissolve clots.

✘ D wrong: Streptokinase is NOT an antibiotic (despite "strepto"-); derived from bacteria but not antibacterial.

61

Tolbutamide belongs to which class? Most Probable

ABiguanide
BFirst-generation
CMeglitinide
DThiazolidinedione

📘 Explanation

✔ Correct — B: Tolbutamide (1956) is a 1st-generation sulphonylurea (short-acting, 6-12 h); chemically an arylsulphonylurea. Others in 1st-gen: chlorpropamide, tolazamide, acetohexamide. 2nd gen (more potent, longer) = glibenclamide (glyburide), glipizide, gliclazide, glimepiride. Close K-ATP channels on β-cell → depolarisation → ↑ insulin release.

✘ A wrong: Biguanides = metformin, phenformin.

✘ C wrong: Meglitinides = repaglinide, nateglinide.

✘ D wrong: Thiazolidinediones = pioglitazone, rosiglitazone (PPAR-γ agonists).

62

Metformin lowers blood glucose mainly by: GPAT 2021

AInhibiting hepatic gluconeogenesis
BStimulating pancreatic β-cells
CBlocking SGLT-2 in kidney
DActivating PPAR-γ

📘 Explanation

✔ Correct — A: Metformin (biguanide derived from galegine of Galega officinalis) activates AMPK in hepatocytes → ↓ gluconeogenesis, ↓ lipogenesis, ↑ insulin sensitivity, ↑ glucose uptake in muscle. First-line for T2DM, does not cause hypoglycaemia alone, promotes weight loss. ADR: GI upset, lactic acidosis (rare; stop if eGFR < 30), B12 deficiency (long-term).

✘ B wrong: β-cell stimulation = sulphonylureas, meglitinides.

✘ C wrong: SGLT-2 inhibitors = empagliflozin, dapagliflozin, canagliflozin.

✘ D wrong: PPAR-γ agonism = TZDs (pioglitazone).

63

DPP-4 (dipeptidyl peptidase-4) inhibitors work by: GPAT 2021

ADirectly releasing insulin
BBlocking α-glucosidase in gut
CPreventing degradation of GLP-1 and GIP
DInhibiting glucagon release directly

📘 Explanation

✔ Correct — C: Gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin, teneligliptin) inhibit DPP-4 → prevent degradation of endogenous incretins GLP-1 and GIP → ↑ glucose-dependent insulin secretion + ↓ glucagon. Weight-neutral; low hypoglycaemia risk; mild potency (~ 0.5-0.8 % HbA1c ↓). ADR: pancreatitis, joint pain, bullous pemphigoid.

✘ A wrong: Sulphonylureas release insulin directly (via K-ATP closure).

✘ B wrong: α-glucosidase inhibitors = acarbose, miglitol.

✘ D wrong: DPP-4 inhibitors don't directly inhibit glucagon; they act via GLP-1.

64

Empagliflozin lowers glucose by: Most Probable

AAMPK activation
BK-ATP channel closure
CDPP-4 inhibition
DBlocking SGLT-2 in renal

📘 Explanation

✔ Correct — D: Empagliflozin (and dapagliflozin, canagliflozin, ertugliflozin) — "gliflozins" — selectively inhibit SGLT-2 (90 % of renal glucose reabsorption) → ~ 60-100 g glucose excreted in urine daily → HbA1c ↓ ~ 0.7-1.0 %. Added benefits: weight loss, BP ↓, cardioprotection (EMPA-REG), renoprotection (EMPA-KIDNEY, DAPA-CKD). ADR: genitourinary mycoses, volume depletion, euglycaemic DKA, Fournier's gangrene (rare), amputations (canagliflozin).

✘ A wrong: AMPK = metformin.

✘ B wrong: K-ATP closure = sulphonylureas.

✘ C wrong: DPP-4 inhibitors end in "-gliptin".

65

Pioglitazone acts by: Most Probable

APPAR-α activation
BPPAR-γ activation → ↑ adiponectin
Cα-glucosidase inhibition
DGLP-1 agonism

📘 Explanation

✔ Correct — B: Pioglitazone (TZD) is a PPAR-γ nuclear receptor agonist → transcribes genes that enhance insulin sensitivity in adipose, muscle, liver. HbA1c ↓ 0.5-1.4 %. ADR: weight gain (3-5 kg), fluid retention (CHF), fractures in women, bladder cancer risk (pioglitazone, debated), MI (rosiglitazone — withdrawn in EU).

✘ A wrong: PPAR-α = fibrates (fenofibrate, gemfibrozil).

✘ C wrong: α-glucosidase inhibitor = acarbose.

✘ D wrong: GLP-1 agonists = semaglutide, liraglutide, exenatide, dulaglutide.

66

Carbimazole (anti-thyroid) is metabolised to the active form: Most Probable

AMethimazole
BPropylthiouracil
CPerchlorate
DIodide

📘 Explanation

✔ Correct — A: Carbimazole is a prodrug → hydrolysed in plasma to methimazole (thiamazole) which is the active agent. Both are thioamides that inhibit thyroid peroxidase → block iodination of tyrosine & coupling of MIT/DIT → ↓ T3, T4. Long t½ (10-14 h) → once-daily dosing. Propylthiouracil also blocks peripheral T4→T3 conversion (preferred in thyroid storm and first-trimester pregnancy due to lower teratogenicity).

✘ B wrong: Propylthiouracil is a separate drug, not a metabolite of carbimazole.

✘ C wrong: Perchlorate is a historical competitive inhibitor of iodide uptake (rarely used).

✘ D wrong: Iodide (Lugol's, KI) is used in thyroid storm via Wolff-Chaikoff effect — not a metabolite.

67

Mechanism of propylthiouracil: Most Probable

ABlocks TSH receptor
BDestroys thyroid follicles (radioactive)
CInhibits thyroid peroxidase + peripheral
DCompetitive inhibitor of thyroxine

📘 Explanation

✔ Correct — C: PTU inhibits thyroid peroxidase (like methimazole) AND also inhibits peripheral 5'-deiodinase → blocks T4 → T3 conversion. This is why PTU is preferred in thyroid storm (rapid T3 ↓). Shorter t½ (1-2 h) → 3 times daily. Preferred in 1st trimester (methimazole causes aplasia cutis). ADR: agranulocytosis, hepatotoxicity (black-box warning), ANCA vasculitis.

✘ A wrong: TSH receptor antagonists are investigational.

✘ B wrong: Radioactive iodine ¹³¹I destroys follicles.

✘ D wrong: Not a competitive antagonist — PTU blocks synthesis, not action.

68

Sulphonamides inhibit bacterial: Most Probable

ADihydropteroate synthase
BDihydrofolate reductase
CDNA gyrase
DRNA polymerase

📘 Explanation

✔ Correct — A: Sulphonamides are structural analogues of PABA → competitive inhibitors of dihydropteroate synthase → prevent incorporation of PABA into dihydrofolic acid. Bacteria synthesise folate de novo (can't use preformed folate) → selectively affected. Mammals obtain folate from diet → unaffected. Co-trimoxazole = sulphamethoxazole + trimethoprim combines two sequential folate inhibitors → synergy.

✘ B wrong: DHFR inhibitors = trimethoprim, pyrimethamine, methotrexate.

✘ C wrong: DNA gyrase inhibitors = fluoroquinolones.

✘ D wrong: RNA polymerase inhibitor = rifampicin.

69

"Sequential blockade" in cotrimoxazole means: Most Probable

ASimultaneous DNA gyrase + RNA polymerase inhibition
BSulphamethoxazole + trimethoprim
CCell wall + ribosomal inhibition
Dβ-lactam + β-lactamase inhibitor

📘 Explanation

✔ Correct — B: Cotrimoxazole (5:1 SMX:TMP) blocks two sequential enzymes: sulphamethoxazole → DHPS (step 1: PABA + pteridine → dihydropteroate); trimethoprim → DHFR (step 2: dihydrofolate → tetrahydrofolate). The two-step sequential block is bactericidal (each alone is bacteriostatic). Used in UTI, PCP (Pneumocystis), toxoplasmosis.

✘ A wrong: DNA gyrase + RNA polymerase combination is not standard.

✘ C wrong: Cell wall + ribosomal would refer to β-lactam + aminoglycoside synergy.

✘ D wrong: β-lactam + β-lactamase inhibitor = amoxicillin-clavulanate, piperacillin-tazobactam.

70

The core heterocyclic nucleus of fluoroquinolones is: Most Probable

ABenzothiazole
BImidazole
C4-Quinolone
DPyrazolone

📘 Explanation

✔ Correct — C: Fluoroquinolones share a bicyclic 4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4-quinolone) scaffold. Ciprofloxacin — 6-F, 7-piperazinyl, 1-cyclopropyl substitution on quinolone. SAR: 6-F essential for gram-neg activity; 7-substituent (piperazine/pyrrolidine) for gram-pos / anaerobe activity; N1 cyclopropyl (cipro) or methyl; 8-halo (sparfloxacin) for atypicals. Nalidixic acid is the 1,8-naphthyridone prototype.

✘ A wrong: Benzothiazole = riluzole, ethoxazole.

✘ B wrong: Imidazole = metronidazole, azoles antifungals.

✘ D wrong: Pyrazolone = antipyrine, metamizole.

71

Fluoroquinolones inhibit: Most Probable

A50S ribosomal subunit
B30S ribosomal subunit
CCell wall synthesis (peptidoglycan)
DDNA gyrase

📘 Explanation

✔ Correct — D: Fluoroquinolones bind bacterial DNA gyrase (gram-neg primary target) and topoisomerase IV (gram-pos primary target) — both topoisomerase enzymes crucial for DNA supercoiling/decatenation. They become "molecular crowbars" trapping the enzyme on DNA → double-strand breaks → bactericidal. Resistance: mutations in gyrA/parC, efflux pumps.

✘ A wrong: 50S inhibitors = macrolides, chloramphenicol, clindamycin, linezolid.

✘ B wrong: 30S inhibitors = aminoglycosides, tetracyclines.

✘ C wrong: Cell wall inhibitors = β-lactams, vancomycin.

72

Ciprofloxacin is synthesised using which named reaction? Most Probable

AGould-Jacobs reaction
BPfitzinger reaction
CFischer indole synthesis
DHantzsch synthesis

📘 Explanation

✔ Correct — A: Gould-Jacobs reaction is the standard route: aniline + diethyl ethoxymethylenemalonate → anilinomethylenemalonate → thermal cyclisation (250 °C, diphenyl ether) → 4-quinolone-3-carboxylate. For ciprofloxacin — start with 3-chloro-4-fluoroaniline; cyclise to 4-quinolone; N1-cyclopropylation; replace 7-Cl with piperazine; hydrolysis gives cipro.

✘ B wrong: Pfitzinger makes quinoline-4-carboxylic acids from isatin + ketones; different scaffold.

✘ C wrong: Fischer indole synthesis = for indoles (tryptamine derivatives).

✘ D wrong: Hantzsch = dihydropyridines (nifedipine).

73

Which side effect is characteristic of fluoroquinolones, especially in young patients? Most Probable

AOtotoxicity
BTendinitis
CHaemolytic anaemia
DPulmonary fibrosis

📘 Explanation

✔ Correct — B: Fluoroquinolones carry FDA black-box warning for tendon rupture (especially Achilles) and arthropathy in children → contraindicated in children < 18 and pregnancy. Also QT prolongation, peripheral neuropathy, aortic aneurysm/dissection risk, C. diff colitis, hepatotoxicity.

✘ A wrong: Ototoxicity = aminoglycosides (streptomycin, gentamicin).

✘ C wrong: Haemolytic anaemia in G6PD deficiency = primaquine, dapsone, sulphonamides, nitrofurantoin.

✘ D wrong: Pulmonary fibrosis = bleomycin, amiodarone, nitrofurantoin, methotrexate.

74

Which sulphonamide is used topically for burns? Most Probable

ASulphadiazine (oral)
BSulphamethoxazole
CSilver sulphadiazine (cream)
DSulphasalazine

📘 Explanation

✔ Correct — C: Silver sulphadiazine (SSD, Silvadene®) 1 % cream is the standard topical antibacterial for burns — slowly releases Ag⁺ and sulphadiazine → broad-spectrum (Pseudomonas, Staph, Candida). Alternatives: mafenide acetate, povidone iodine.

✘ A wrong: Oral sulphadiazine is for toxoplasmosis (with pyrimethamine).

✘ B wrong: SMX is the oral component of cotrimoxazole.

✘ D wrong: Sulphasalazine is for ulcerative colitis, rheumatoid arthritis (prodrug of 5-ASA).

75

Insulin glargine's long action comes from: Most Probable

AShift of isoelectric point
BZinc-insulin complex
CPEGylation
DFatty acid conjugation

📘 Explanation

✔ Correct — A: Insulin glargine (Lantus) has A21 Asn → Gly and two extra Arg at the C-end of B-chain → isoelectric point shifts from ~ 5.4 to ~ 7.0. Formulated at acidic pH 4 → soluble; at physiological pH 7.4 in SC tissue → precipitates → slow release → ~ 24 h duration, peakless. Detemir: myristic acid attached to B29-Lys (albumin binding). Degludec: hexadecanedioic acid-γ-Glu (fatty acid conjugation) → multi-hexameric depot, t½ ≈ 25 h.

✘ B wrong: Zinc-insulin (Lente, ultralente) was older intermediate/long approach — now obsolete.

✘ C wrong: PEGylation is not used for insulin (used for G-CSF, IFN).

✘ D wrong: Fatty acid conjugation is detemir & degludec, not glargine.

76

Which insulin analogue has the FASTEST onset? Practice Question

AGlargine
BNPH
CLispro
DRegular insulin

📘 Explanation

✔ Correct — C: Rapid-acting analogues — lispro (Humalog), aspart (NovoRapid), glulisine (Apidra) — modified at B28-29 region of B-chain to prevent hexamer formation → monomers absorbed rapidly. Onset ~ 10-15 min, peak 1-2 h, duration 3-5 h. Given just before or with meals.

✘ A wrong: Glargine = long-acting (onset 2-4 h, flat, 24 h).

✘ B wrong: NPH = intermediate (onset 1-2 h, peak 4-10 h, 12-18 h).

✘ D wrong: Regular (soluble) onset 30-60 min, peak 2-4 h; slower than analogues.

77

Which oral hypoglycaemic has a risk of fatal lactic acidosis? Most Probable

AGlibenclamide
BMetformin
CPioglitazone
DSitagliptin

📘 Explanation

✔ Correct — B: Biguanides impair mitochondrial respiration → ↑ anaerobic glycolysis → ↑ lactate. Phenformin (withdrawn in 1970s) caused high incidence of fatal lactic acidosis (~ 64/100,000). Metformin rarely causes it (~ 3/100,000 patient-years) — avoid if eGFR < 30, liver failure, severe CHF, sepsis, tissue hypoxia; hold during IV contrast in patients with eGFR 30-60.

✘ A wrong: Glibenclamide's main ADR is hypoglycaemia, not acidosis.

✘ C wrong: Pioglitazone — fluid retention, heart failure, fractures.

✘ D wrong: Sitagliptin — pancreatitis, arthralgia; not lactic acidosis.

78

Which antidiabetic is contraindicated in heart failure? Practice Question

AMetformin
BSitagliptin
CEmpagliflozin
DPioglitazone

📘 Explanation

✔ Correct — D: Pioglitazone causes sodium & water retention (PPAR-γ on collecting duct ENaC) → worsens/precipitates CHF. Black-box warning. Contraindicated in NYHA III-IV.

✘ A wrong: Metformin was historically cautioned but now recommended in HFrEF (stable; eGFR > 30); not contraindicated per se.

✘ B wrong: Saxagliptin (not sitagliptin) had modest CHF signal (SAVOR-TIMI).

✘ C wrong: Empagliflozin is REDUCES HF hospitalisations (EMPEROR-Reduced, EMPA-REG) → now a cornerstone HFrEF therapy even in non-diabetics.

79

Which sulphonamide is used for ulcerative colitis? Most Probable

ASulphadiazine
BSulphasalazine
CSulphamethoxazole
DSulphacetamide

📘 Explanation

✔ Correct — B: Sulphasalazine — a prodrug; colonic bacteria (azoreductase) cleave the azo bond → release 5-ASA (mesalamine, the active anti-inflammatory) + sulphapyridine (mostly inactive carrier). Used for IBD (UC, Crohn's), rheumatoid arthritis. ADR from sulphapyridine — rash, GI, oligospermia, agranulocytosis. Newer: pure mesalamine (Asacol, Pentasa) — no sulpha-related ADR.

✘ A wrong: Sulphadiazine → toxoplasmosis.

✘ C wrong: SMX → UTI, PCP.

✘ D wrong: Sulphacetamide is used as eye drops for conjunctivitis.

80

Chlorthalidone differs from HCTZ in: GPAT 2021

ADifferent mechanism
BDifferent dosing frequency (TID vs QD)
CLonger duration (~ 48-72 h) due to RBC binding
DIs a loop diuretic, not thiazide

📘 Explanation

✔ Correct — C: Chlorthalidone is a thiazide-like (phthalimidine) diuretic — same mechanism (Na-Cl symporter in DCT) as HCTZ but binds tightly to erythrocyte carbonic anhydrase → t½ ~ 40 h vs HCTZ ~ 8-15 h. Evidence (ALLHAT, SHEP) suggests chlorthalidone is more effective at BP lowering than HCTZ at equivalent doses.

✘ A wrong: Same mechanism.

✘ B wrong: Both once daily.

✘ D wrong: Chlorthalidone is thiazide-LIKE (phthalimidine), acts like thiazide — not a loop diuretic.

81

Isoniazid (INH) inhibits synthesis of: Most Probable

AMycolic acids (cell wall)
BDNA (inhibits DNA-dependent RNA polymerase)
CFolic acid
DPeptidoglycan (like penicillin)

📘 Explanation

✔ Correct — A: INH is a prodrug activated by mycobacterial KatG (catalase-peroxidase) → isonicotinoyl radical that forms adduct with NAD → inhibits InhA (enoyl-ACP reductase) → blocks mycolic acid synthesis → defective cell wall. Bactericidal against replicating bacilli. Resistance: katG mutations (loss of activation), inhA promoter mutations. ADR: peripheral neuropathy (give pyridoxine), hepatitis, drug-induced lupus.

✘ B wrong: Rifampicin inhibits DNA-dependent RNA polymerase.

✘ C wrong: Folate inhibitors = sulphonamides, trimethoprim, PAS.

✘ D wrong: Peptidoglycan = β-lactams, not INH (mycobacteria have mycolic-acid cell wall).

82

Rifampicin inhibits: Most Probable

AMycolic acid synthesis
BBacterial DNA-dependent RNA
CArabinogalactan synthesis
DFatty-acid synthase

📘 Explanation

✔ Correct — B: Rifampicin (semi-synthetic from Amycolatopsis mediterranei) binds bacterial RNA polymerase β-subunit (rpoB gene) → blocks RNA synthesis. Bactericidal, sterilising effect on dormant bacilli. Strong CYP3A4 inducer — interactions with OCPs (failure), warfarin, HIV drugs. Colours secretions orange-red.

✘ A wrong: Mycolic acid = INH.

✘ C wrong: Arabinogalactan = ethambutol (inhibits arabinosyl transferase, embB).

✘ D wrong: FAS II = INH path; FAS I = mammalian.

83

Ethambutol's main ADR: Most Probable

AHepatotoxicity
BPeripheral neuropathy
CRetrobulbar
DOtotoxicity

📘 Explanation

✔ Correct — C: Ethambutol causes dose-dependent retrobulbar (optic) neuritis → ↓ visual acuity and red-green colour blindness. Monitor visual fields / Ishihara plates before & during therapy. Mnemonic: "E for Eye". Dose-reduce if CrCl < 50. Hyperuricaemia is another ADR.

✘ A wrong: Hepatotoxicity = INH, rifampicin, pyrazinamide.

✘ B wrong: Peripheral neuropathy = INH (prevent with pyridoxine).

✘ D wrong: Ototoxicity = streptomycin, kanamycin, amikacin (aminoglycosides).

84

Dapsone is chemically: Most Probable

AA sulphonamide
BA quinolone
CA rifamycin analogue
D4,4'-diaminodiphenyl

📘 Explanation

✔ Correct — D: Dapsone (DDS) = 4,4'-diaminodiphenyl sulphone — PABA antagonist; inhibits DHPS (same target as sulphonamides) but chemically a sulphone, not sulphonamide. Used in leprosy (WHO MDT), dermatitis herpetiformis, PCP prophylaxis. ADR: haemolysis (G6PD), methaemoglobinaemia, dapsone hypersensitivity syndrome (DRESS).

✘ A wrong: Sulphonamides have -SO₂NH₂ group (dapsone has -SO₂- bridge without NH₂ directly attached to SO₂ as primary sulphonamide).

✘ B wrong: Quinolone = fluoroquinolones.

✘ C wrong: Rifamycin = rifampin structure.

85

Azoles (ketoconazole, fluconazole) inhibit fungal: Most Probable

Aβ-glucan synthase
B14-α-demethylase
CDNA polymerase
DDHFR

📘 Explanation

✔ Correct — B: Azole antifungals (imidazoles — ketoconazole, clotrimazole, miconazole; triazoles — fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole) inhibit fungal cytochrome P450 enzyme lanosterol 14-α-demethylase (CYP51) → blocks conversion of lanosterol to ergosterol → depletes ergosterol + accumulates toxic intermediates → disrupts fungal membrane.

✘ A wrong: β-glucan synthase inhibitors = echinocandins (caspofungin, micafungin, anidulafungin).

✘ C wrong: Azoles don't target DNA polymerase.

✘ D wrong: DHFR inhibitors = trimethoprim, methotrexate.

86

Amphotericin B binds to: Most Probable

AErgosterol in fungal membrane
BLanosterol 14-α demethylase
CSqualene epoxidase
DFungal microtubules

📘 Explanation

✔ Correct — A: Amphotericin B (polyene macrolide, from Streptomyces nodosus) binds ergosterol in fungal membrane → self-assembles into pores → K⁺ and Mg²⁺ leak → cell death. Broad-spectrum fungicidal. ADR: nephrotoxicity ("ampho-terrible"), infusion reactions (fever, chills), hypokalaemia, hypomagnesaemia. Lipid formulations (liposomal AmBisome) less toxic.

✘ B wrong: CYP51 = azoles.

✘ C wrong: Squalene epoxidase = terbinafine, naftifine (allylamines).

✘ D wrong: Microtubule inhibition = griseofulvin.

87

Acyclovir is activated by: Most Probable

AHost thymidine kinase
BReverse transcriptase
CViral thymidine kinase
DViral protease

📘 Explanation

✔ Correct — C: Acyclovir (acyclic guanosine analogue) is preferentially phosphorylated by viral thymidine kinase (HSV, VZV) to acyclovir monophosphate → host kinases convert to triphosphate → incorporates into viral DNA → chain termination (lacks 3'-OH). Selective for virus-infected cells. Resistance: TK-deficient mutants (treat with foscarnet). Prodrug valacyclovir improves oral bioavailability.

✘ A wrong: Host TK is 3000× less efficient at phosphorylating acyclovir → minimal activation in uninfected cells.

✘ B wrong: Reverse transcriptase is HIV-encoded (zidovudine, tenofovir target).

✘ D wrong: Protease is target of protease inhibitors (ritonavir).

88

Zidovudine (AZT) is a: Most Probable

ANon-nucleoside reverse transcriptase inhibitor
BNucleoside reverse transcriptase inhibitor
CProtease inhibitor
DIntegrase strand transfer inhibitor

📘 Explanation

✔ Correct — B: Zidovudine (AZT, 3'-azido-2',3'-dideoxythymidine) is the first approved anti-HIV drug (1987). A thymidine analogue — phosphorylated by host thymidine kinase → AZT-TP → competes with dTTP for HIV reverse transcriptase → chain termination (N₃ replaces 3'-OH). ADR: anaemia, myopathy, lactic acidosis, lipodystrophy. Mainly replaced by tenofovir now.

✘ A wrong: NNRTIs = nevirapine, efavirenz, rilpivirine, doravirine.

✘ C wrong: PIs = ritonavir, lopinavir, atazanavir, darunavir ("-navir").

✘ D wrong: INSTIs = raltegravir, dolutegravir, bictegravir, elvitegravir ("-gravir").

89

Cyclophosphamide is a prodrug; active metabolite is: Most Probable

APhosphoramide
BIfosfamide
CMesna
DCarmustine

📘 Explanation

✔ Correct — A: Cyclophosphamide is hydroxylated by hepatic CYP2B6 → 4-hydroxycyclophosphamide ↔ aldophosphamide → spontaneously splits into phosphoramide mustard (active alkylator, alkylates N7-guanine) + acrolein (urotoxic metabolite — causes haemorrhagic cystitis). MESNA (sodium 2-mercaptoethane sulphonate) binds acrolein in urine to prevent bladder toxicity.

✘ B wrong: Ifosfamide is a separate drug (a 3-methyl analogue — also needs mesna).

✘ C wrong: Mesna is the PROTECTIVE agent, not active metabolite.

✘ D wrong: Carmustine is a nitrosourea alkylator, unrelated.

90

Methotrexate inhibits: Most Probable

ATopoisomerase II
BTubulin polymerisation
CDihydrofolate reductase
DThymidylate synthase directly

📘 Explanation

✔ Correct — C: Methotrexate (4-amino-10-methyl folic acid) is a folate analogue — potent competitive inhibitor of DHFR → ↓ tetrahydrofolate → ↓ thymidylate & purine synthesis → S-phase specific. Uses: ALL, choriocarcinoma, osteosarcoma; non-oncology — RA, psoriasis, ectopic pregnancy, medical abortion. Antidote: leucovorin (folinic acid) rescue. ADR: mucositis, bone marrow, hepatitis, pneumonitis.

✘ A wrong: Topo II inhibitors = doxorubicin, etoposide, teniposide.

✘ B wrong: Tubulin inhibitors = vincristine, paclitaxel, colchicine.

✘ D wrong: Thymidylate synthase direct inhibition = 5-fluorouracil (via FdUMP metabolite).

91

5-Fluorouracil is converted to which active metabolite? Most Probable

A5-FU itself
BFdUMP
CMethotrexate
D6-mercaptopurine

📘 Explanation

✔ Correct — B: 5-FU is converted to FdUMP which binds covalently to thymidylate synthase (with N5,N10-methylene THF) forming a ternary complex → blocks dTMP synthesis → "thymineless death". Also converted to FUTP → mis-incorporates into RNA. S-phase active. Uses: colorectal, breast, head and neck, pancreatic cancer. Capecitabine is an oral 5-FU prodrug activated in tumour by thymidine phosphorylase.

✘ A wrong: 5-FU itself is prodrug — needs metabolism.

✘ C wrong: Methotrexate is a separate folate analogue.

✘ D wrong: 6-MP is a purine analogue (for ALL, IBD), not 5-FU metabolite.

92

Vincristine/vinblastine act by: Most Probable

ABinding tubulin → inhibit microtubule POLYMERISATION
BStabilising microtubules (prevent depolymerisation)
CAlkylating DNA
DInhibiting DHFR

📘 Explanation

✔ Correct — A: Vinca alkaloids (vincristine, vinblastine, vinorelbine, vindesine — from Catharanthus roseus) bind β-tubulin at vinca site → prevent polymerisation → cells arrest in M-phase. Contrast: taxanes (paclitaxel, docetaxel) STABILISE microtubules (prevent depolymerisation) → same M-phase arrest via opposite mechanism. Vincristine → peripheral neuropathy (dose-limiting). Vinblastine → myelosuppression.

✘ B wrong: Microtubule stabilisation = taxanes, epothilones, eribulin.

✘ C wrong: Alkylation = cyclophosphamide, cisplatin, BCNU.

✘ D wrong: DHFR = methotrexate.

93

Imatinib is a TKI directed against: Most Probable

AEGFR
BHER2
CVEGFR
DBCR-ABL fusion

📘 Explanation

✔ Correct — D: Imatinib (Gleevec) binds ATP-pocket of BCR-ABL fusion kinase formed by the Philadelphia chromosome (t[9;22]) in CML — 95 % 10-year survival; also inhibits c-KIT (GIST) and PDGFR. Landmark targeted therapy (Nobel-level impact). Resistance: T315I gatekeeper mutation → 2nd-gen TKIs (dasatinib, nilotinib) or ponatinib (3rd gen, covers T315I).

✘ A wrong: EGFR = erlotinib, gefitinib, osimertinib (NSCLC), cetuximab, panitumumab (mAbs).

✘ B wrong: HER2 = trastuzumab (mAb), lapatinib, neratinib (TKIs).

✘ C wrong: VEGFR = sorafenib, sunitinib, pazopanib, axitinib; bevacizumab (mAb).

94

Allopurinol is a: Most Probable

AXanthine oxidase inhibitor
BUricosuric agent
CUrate oxidase
DMicrotubule inhibitor

📘 Explanation

✔ Correct — A: Allopurinol (pyrazolo[3,4-d]pyrimidine, hypoxanthine analogue) and its metabolite oxypurinol inhibit xanthine oxidase → ↓ uric acid synthesis. Used for chronic gout, tumour lysis syndrome, Lesch-Nyhan. Avoid in HLA-B*58:01 positive (SJS/TEN). Reduce dose of 6-MP / azathioprine (XO metabolises them — inhibition → ↑ toxicity).

✘ B wrong: Uricosurics = probenecid, sulphinpyrazone, benzbromarone, lesinurad.

✘ C wrong: Urate oxidase = rasburicase (recombinant), pegloticase — converts uric acid to soluble allantoin.

✘ D wrong: Microtubule inhibitor = colchicine (acute gout).

95

Colchicine acts by: Most Probable

AInhibiting xanthine oxidase
BBinding tubulin → inhibits neutrophil
CIncreasing uric acid excretion
DBlocking prostaglandin synthesis

📘 Explanation

✔ Correct — B: Colchicine (from Colchicum autumnale) binds β-tubulin → prevents microtubule polymerisation → inhibits leukocyte migration, phagocytosis, IL-1β release → reduces inflammation of acute gout. Useful in FMF, pericarditis, Behçet's. Narrow TI; GI (diarrhoea) is first sign of toxicity; fatal overdose. CYP3A4 + P-gp substrate (interactions with macrolides, statins).

✘ A wrong: XO inhibitor = allopurinol, febuxostat.

✘ C wrong: Uricosurics = probenecid.

✘ D wrong: NSAIDs block PG — separate class for acute gout.

96

Iohexol is chemically classified as: Most Probable

AIonic high-osmolar contrast
BIonic low-osmolar contrast
CNon-ionic low-osmolar iodinated
DGadolinium MRI contrast

📘 Explanation

✔ Correct — C: Iohexol (Omnipaque) is a non-ionic monomer (3 iodine atoms per molecule, no ionisable carboxyl) — low osmolar (~ 670-850 mOsm/kg) — safer than older ionic high-osmolar agents (diatrizoate ~ 1500 mOsm/kg). Lower rates of contrast reactions & contrast-induced nephropathy. Iopamidol similar. Iodixanol is iso-osmolar dimer.

✘ A wrong: Ionic high-osmolar = diatrizoate, iothalamate (older).

✘ B wrong: Ionic low-osmolar = ioxaglate.

✘ D wrong: Gadolinium agents (gadopentetate, gadobutrol) are for MRI, not X-ray.

97

Technetium-99m is used because of: Practice Question

A6-h half-life and pure γ-emission
Bβ-emission suitable for therapy
CAlpha emission
DLong half-life (weeks)

📘 Explanation

✔ Correct — A: ⁹⁹ᵐTc is the "workhorse of nuclear medicine" because: (i) t½ = 6 hours — enough for imaging, but short enough to limit patient dose; (ii) pure gamma emitter at 140 keV — ideal for γ-cameras; (iii) easily obtained from ⁹⁹Mo/⁹⁹ᵐTc generator ("moly-cow"); (iv) easily binds to diverse ligands → bone (MDP), heart (sestamibi), renal (DTPA, MAG3), thyroid (pertechnetate), liver, lung scans. Covers 80 % of SPECT imaging worldwide.

✘ B wrong: β-emitters are therapy radionuclides (¹³¹I, ⁹⁰Y, ¹⁷⁷Lu).

✘ C wrong: α-emitters = ²²³Ra (Xofigo) for bone metastases — therapeutic.

✘ D wrong: Long half-life is unsuitable for diagnostic (radiation burden).

98

Which antileprosy drug causes reddish-black skin discolouration? Most Probable

ADapsone
BClofazimine
CRifampicin
DMinocycline

📘 Explanation

✔ Correct — B: Clofazimine (iminophenazine dye) deposits in skin & macrophages → reddish-brown to black discolouration of skin (especially lesions) & body fluids. Component of WHO-MDT for multibacillary leprosy. Also has anti-inflammatory effects; controls erythema nodosum leprosum (ENL).

✘ A wrong: Dapsone causes haemolysis, methaemoglobinaemia, DRESS — not characteristic skin colour change.

✘ C wrong: Rifampicin colours body fluids orange-red (tears, urine, sweat), not skin discoloration in this sense.

✘ D wrong: Minocycline can cause bluish-grey pigmentation (especially with long use) but not typical first-line anti-leprosy drug.

99

Which anticancer drug is known for cumulative CARDIOTOXICITY (total dose-related)? Most Probable

ACisplatin
BVincristine
CBleomycin
DDoxorubicin

📘 Explanation

✔ Correct — D: Doxorubicin (and daunorubicin, epirubicin, idarubicin — anthracyclines) cause dose-cumulative dilated cardiomyopathy via free-radical damage to mitochondria. Maximum cumulative dose ~ 450-550 mg/m² for doxorubicin. Dexrazoxane (iron chelator) is cardioprotective. Liposomal formulation (Doxil) reduces cardiac toxicity.

✘ A wrong: Cisplatin → nephrotoxicity (most), ototoxicity, nausea.

✘ B wrong: Vincristine → peripheral neuropathy.

✘ C wrong: Bleomycin → pulmonary fibrosis (dose-cumulative too, > 400 units).

100

Tamoxifen is a: Most Probable

AAromatase inhibitor
BSelective estrogen receptor modulator
CLHRH agonist
DAndrogen receptor antagonist

📘 Explanation

✔ Correct — B: Tamoxifen is a triphenylethylene SERM — antagonist at breast estrogen receptors (adjuvant in ER+ breast cancer), partial agonist at bone (protects bone density) and endometrium (↑ endometrial cancer risk). Prodrug — metabolised by CYP2D6 to active endoxifen. Other SERMs: raloxifene (no endometrial risk, osteoporosis); clomiphene (fertility).

✘ A wrong: Aromatase inhibitors = anastrozole, letrozole, exemestane (post-menopausal ER+ BC).

✘ C wrong: LHRH agonists = leuprolide, goserelin (↓ sex hormones; prostate cancer, endometriosis).

✘ D wrong: Androgen blockers = bicalutamide, enzalutamide (prostate cancer).

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BP501T · MEDICINAL CHEMISTRY II

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