Diuretics – classification, SAR, mechanism, uses MCQs With Answer

Diuretics are a diverse group of drugs that increase renal water and electrolyte excretion. This introduction covers classification, structure–activity relationships (SAR), mechanisms of action, clinical uses, adverse effects and key pharmacology concepts relevant to B.Pharm students. Major classes include loop diuretics, thiazides, potassium-sparing agents, carbonic anhydrase inhibitors and osmotic diuretics. Understanding SAR (sulfonamide groups in thiazides/CAIs, arylacetic acid in loops, guanidinium in amiloride) helps predict potency, selectivity and side effects. Mechanisms involve targets such as NKCC2, NCC, ENaC and carbonic anhydrase. Clinical applications span hypertension, heart failure, edema, glaucoma, and altitude sickness. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which segment of the nephron is the primary site of action for loop diuretics?

• Proximal convoluted tubule
• Thick ascending limb of loop of Henle
• Distal convoluted tubule
• Collecting duct

Correct Answer: Thick ascending limb of loop of Henle

Q2. Which transporter is inhibited by thiazide diuretics?

• Na+/K+/2Cl− cotransporter (NKCC2)
• Epithelial sodium channel (ENaC)
• Na+/Cl− cotransporter (NCC)
• Na+/H+ exchanger (NHE3)

Correct Answer: Na+/Cl− cotransporter (NCC)

Q3. Which structural feature is essential in classical thiazide SAR for diuretic activity?

• A benzothiadiazine ring with a sulfonamide group
• A carboxylic acid attached to an aromatic ring
• A guanidinium moiety
• An ether-linked sugar

Correct Answer: A benzothiadiazine ring with a sulfonamide group

Q4. Which diuretic would be preferred in a patient with severe sulfonamide allergy?

• Furosemide
• Hydrochlorothiazide
• Ethacrynic acid
• Acetazolamide

Correct Answer: Ethacrynic acid

Q5. Which diuretic class is most likely to cause hypokalemia and metabolic alkalosis?

• Carbonic anhydrase inhibitors
• Loop diuretics and thiazides
• Potassium-sparing diuretics
• Osmotic diuretics

Correct Answer: Loop diuretics and thiazides

Q6. Acetazolamide exerts its diuretic effect primarily by inhibiting:

• Aldosterone receptors in collecting duct
• Carbonic anhydrase in proximal tubule
• NKCC2 in thick ascending limb
• NCC in distal tubule

Correct Answer: Carbonic anhydrase in proximal tubule

Q7. Which diuretic is commonly used to reduce intraocular pressure in acute angle-closure glaucoma?

• Hydrochlorothiazide
• Acetazolamide
• Spironolactone
• Bumetanide

Correct Answer: Acetazolamide

Q8. Which of the following best describes the SAR feature that increases loop diuretic potency (e.g., bumetanide vs furosemide)?

• Replacement of sulfonamide by carboxamide decreases potency
• An electron-withdrawing substituent on the aromatic ring increases potency
• Removal of aromatic ring increases potency
• Adding a bulky alkyl chain at the carboxylate drastically reduces potency

Correct Answer: An electron-withdrawing substituent on the aromatic ring increases potency

Q9. Amiloride’s diuretic action is primarily due to inhibition of:

• Carbonic anhydrase
• NKCC2 transporter
• ENaC in the collecting duct
• Na+/Cl− cotransporter in distal tubule

Correct Answer: ENaC in the collecting duct

Q10. Which diuretic class is most useful in treating edema associated with left ventricular failure?

• Loop diuretics
• Carbonic anhydrase inhibitors
• Thiazides
• Potassium-sparing diuretics only

Correct Answer: Loop diuretics

Q11. Which adverse effect is characteristically associated with thiazide diuretics?

• Hypouricemia
• Hyperglycemia and hyperlipidemia
• Hyperkalemia
• Severe metabolic acidosis

Correct Answer: Hyperglycemia and hyperlipidemia

Q12. Which statement about spironolactone’s mechanism is correct?

• Directly blocks ENaC channels
• Inhibits aldosterone receptors, reducing ENaC and Na+/K+ ATPase expression
• Inhibits carbonic anhydrase activity
• Blocks NKCC2 transporter in the loop

Correct Answer: Inhibits aldosterone receptors, reducing ENaC and Na+/K+ ATPase expression

Q13. Diuretic-induced hyponatremia is most commonly a complication of:

• Loop diuretics alone
• Thiazide diuretics
• Carbonic anhydrase inhibitors
• Osmotic diuretics

Correct Answer: Thiazide diuretics

Q14. Which diuretic increases urinary calcium excretion the most?

• Thiazides reduce urinary calcium excretion
• Loop diuretics increase urinary calcium excretion
• Potassium-sparing diuretics increase urinary calcium excretion
• Carbonic anhydrase inhibitors have the largest effect on calcium

Correct Answer: Loop diuretics increase urinary calcium excretion

Q15. Which interaction is clinically important when combining NSAIDs with loop or thiazide diuretics?

• NSAIDs potentiate diuretic-induced hypokalemia
• NSAIDs reduce diuretic efficacy by inhibiting prostaglandin-mediated renal blood flow
• NSAIDs increase renal clearance of diuretics leading to toxicity reduction
• NSAIDs convert thiazides into active metabolites

Correct Answer: NSAIDs reduce diuretic efficacy by inhibiting prostaglandin-mediated renal blood flow

Q16. Which diuretic is most appropriate for prevention of acute mountain sickness?

• Bumetanide
• Acetazolamide
• Spironolactone
• Hydrochlorothiazide

Correct Answer: Acetazolamide

Q17. Which property of ethacrynic acid distinguishes it from most other loop diuretics?

• It is a carbonic anhydrase inhibitor
• It lacks a sulfonamide group
• It blocks ENaC channels
• It is potassium-sparing

Correct Answer: It lacks a sulfonamide group

Q18. Which change in serum electrolytes is expected with spironolactone therapy?

• Hypokalemia and metabolic alkalosis
• Hyperkalemia and metabolic acidosis
• Hyperkalemia and mild metabolic acidosis or neutral pH
• Hyponatremia and hypokalemia

Correct Answer: Hyperkalemia and mild metabolic acidosis or neutral pH

Q19. Which structural feature is common and important for carbonic anhydrase inhibitor activity?

• Carboxylic acid adjacent to aromatic ring
• Sulfonamide moiety that binds the zinc in the enzyme active site
• Guanidinium group interacting with ENaC
• A benzothiadiazine nucleus

Correct Answer: Sulfonamide moiety that binds the zinc in the enzyme active site

Q20. Diuretic resistance in heart failure is often due to:

• Enhanced distal nephron sodium reabsorption and reduced renal perfusion
• Excessive inhibition of aldosterone receptors
• Overuse of carbonic anhydrase inhibitors alone
• Primary ENaC overactivity independent of upstream sodium delivery

Correct Answer: Enhanced distal nephron sodium reabsorption and reduced renal perfusion

Q21. Which diuretic is best used for reducing cerebral edema or raised intracranial pressure?

• Mannitol (osmotic diuretic)
• Thiazide diuretics
• Spironolactone
• Acetazolamide

Correct Answer: Mannitol (osmotic diuretic)

Q22. Which transporter mutation would reduce the efficacy of thiazide diuretics?

• Loss-of-function mutation in NKCC2
• Loss-of-function mutation in NCC (SLC12A3)
• Gain-of-function in ENaC
• Loss-of-function in carbonic anhydrase II

Correct Answer: Loss-of-function mutation in NCC (SLC12A3)

Q23. Which combination is most likely to cause significant hyperkalemia?

• Loop diuretic + thiazide
• ACE inhibitor + potassium-sparing diuretic
• Carbonic anhydrase inhibitor + loop diuretic
• Thiazide + loop diuretic

Correct Answer: ACE inhibitor + potassium-sparing diuretic

Q24. Bumetanide compared to furosemide is:

• Less potent with slower onset
• More potent per mg and more bioavailable
• Has no sulfonamide and is safer in sulfa allergy
• Primarily a carbonic anhydrase inhibitor

Correct Answer: More potent per mg and more bioavailable

Q25. Which diuretic class can be used to treat nephrogenic diabetes insipidus caused by lithium?

• Loop diuretics worsen diabetes insipidus
• Thiazide diuretics reduce polyuria by inducing mild hypovolemia
• Carbonic anhydrase inhibitors are first-line
• Potassium-sparing diuretics are preferred

Correct Answer: Thiazide diuretics reduce polyuria by inducing mild hypovolemia

Q26. Which lab finding is a hallmark of carbonic anhydrase inhibitor therapy?

• Metabolic alkalosis with hypokalemia
• Metabolic acidosis with normal anion gap and hyperchloremia
• Severe hyponatremia without acid–base change
• Marked hypercalcemia

Correct Answer: Metabolic acidosis with normal anion gap and hyperchloremia

Q27. Which diuretic’s SAR includes a guanidinium-like basic group essential for ENaC binding?

• Triamterene
• Amiloride
• Hydrochlorothiazide
• Furosemide

Correct Answer: Amiloride

Q28. Which clinical use is most specific to loop diuretics compared with thiazides?

• Long-term hypertension control
• Treatment of hypercalcemia by promoting calciuresis
• Management of glaucoma
• Correction of metabolic alkalosis

Correct Answer: Treatment of hypercalcemia by promoting calciuresis

Q29. Which pharmacokinetic property is important for rapid IV diuresis in pulmonary edema?

• Low oral bioavailability
• Rapid onset of action and high IV potency
• Predominantly hepatic elimination to avoid renal effects
• Long half-life for sustained effect

Correct Answer: Rapid onset of action and high IV potency

Q30. Which mechanism explains how thiazides lower blood pressure chronically beyond immediate diuresis?

• Continued natriuresis only
• Reduction of peripheral vascular resistance and direct vasodilatory effects with time
• Enhanced renin release causing sustained vasoconstriction
• Selective blockade of cardiac β1 receptors

Correct Answer: Reduction of peripheral vascular resistance and direct vasodilatory effects with time

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