Diuretics Practice Questions

Q: Mannitol produces diuresis by which mechanism?

Osmotic effect. ### Explanation **Correct Option: A. Osmotic effect** Mannitol is a pharmacologically inert, non-metabolizable sugar that acts as an **osmotic diuretic**. It is freely filtered at the glomerulus but is not reabsorbed by the renal tubules. Its presence in the tubular lumen creates an osmotic gradient that "holds" water, preventing its reabsorption. This occurs primarily in the **Proximal Convoluted Tubule (PCT)** and the **Descending Limb of the Loop of Henle**, which are highly permeable to water. By increasing the osmolarity of the tubular fluid, it forces the excretion of water along with some sodium. **Why the other options are incorrect:** * **B. Inhibition of Na-K-2Cl cotransporter:** This is the mechanism of **Loop Diuretics** (e.g., Furosemide, Torsemide) acting on the Thick Ascending Limb of the Loop of Henle. * **C. Inhibition of Na-K ATPase:** This is the mechanism of **Cardiac Glycosides** (e.g., Digoxin). While it affects sodium transport, it is not the mechanism for diuresis in clinical practice. * **D. Inhibition of aquaporin channels:** This describes the action of **Vaptans** (e.g., Tolvaptan), which are vasopressin receptor antagonists used to treat hyponatremia. **High-Yield Clinical Pearls for NEET-PG:** * **Route:** Must be given **IV only** (poorly absorbed orally; causes osmotic diarrhea if swallowed). * **Indications:** Primarily used to reduce **Increased Intracranial Pressure (ICP)** in cerebral edema and **Intraocular Pressure (IOP)** in acute glaucoma. * **Contraindications:** Acute Pulmonary Edema and Congestive Heart Failure (due to initial expansion of extracellular fluid volume) and Chronic Renal Failure (Anuria). * **Side Effect:** Can cause initial "expansion hypervolemia" followed by dehydration and hypernatremia.

Q: Which diuretic causes gynecomastia?

Spironolactone. **Explanation:** **Spironolactone** is a potassium-sparing diuretic that acts as a competitive antagonist at the mineralocorticoid (aldosterone) receptor. The development of **gynecomastia** (and other side effects like decreased libido or menstrual irregularities) is due to its lack of receptor specificity. It acts as a non-specific antagonist at **androgen receptors** and increases the peripheral conversion of testosterone to estradiol. This hormonal imbalance leads to the enlargement of male breast tissue. **Analysis of Options:** * **Lubiprostone (A):** This is not a diuretic; it is a chloride channel activator used in the treatment of chronic idiopathic constipation and IBS-C. * **Cimetidine (C):** While Cimetidine is a well-known cause of gynecomastia (via H2 receptor blockade and anti-androgenic effects), it is an **H2-receptor antagonist** used for peptic ulcers, not a diuretic. The question specifically asks for a diuretic. * **Chlorthalidone (D):** This is a thiazide-like diuretic. Its primary side effects include hypokalemia, hyperuricemia, and hyperglycemia, but it does not typically cause gynecomastia. **NEET-PG High-Yield Pearls:** * **Eplerenone** is a selective aldosterone antagonist. It has a much lower affinity for androgen and progesterone receptors, making it the preferred alternative if a patient develops gynecomastia on Spironolactone. * **Mnemonic for Gynecomastia (DISCO):** **D**igoxin, **I**soniazid, **S**pironolactone, **C**imetidine, **O**estrogens/Ketoconazole. * Spironolactone is the drug of choice for **ascites in liver cirrhosis** and is used to reduce mortality in **Congestive Heart Failure (NYHA Class III/IV)**.

Q: Which of the following drugs is used in the management of nephrogenic diabetes insipidus?

Thiazides. ### Explanation **Correct Answer: C. Thiazides** **Mechanism in Nephrogenic Diabetes Insipidus (NDI):** It may seem paradoxical to use a diuretic to treat polyuria, but Thiazides are the mainstay for NDI. They inhibit the $Na^+/Cl^-$ symporter in the distal convoluted tubule, leading to mild volume depletion. This causes a compensatory increase in the reabsorption of sodium and water in the **proximal tubule**. Consequently, less fluid reaches the distal parts of the nephron, reducing the total urine volume excreted. **Analysis of Incorrect Options:** * **A. Mannitol:** An osmotic diuretic used primarily to reduce intracranial or intraocular pressure. It would worsen polyuria in DI. * **B. Spironolactone:** A potassium-sparing diuretic (aldosterone antagonist) used in cirrhosis, heart failure, and Conn’s syndrome. It has no role in treating DI. * **D. Demeclocycline:** A tetracycline derivative that actually **causes** nephrogenic DI by inhibiting ADH action in the collecting duct. It is used to treat SIADH (Syndrome of Inappropriate Antidiuretic Hormone). **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** For Central DI, the DOC is **Desmopressin (dDAVP)**. For Nephrogenic DI, the DOC is **Thiazides** (often Amiloride if caused by Lithium). * **Lithium-Induced NDI:** **Amiloride** is specifically preferred because it blocks the ENaC channels through which Lithium enters the collecting duct cells. * **Prostaglandin Inhibitors:** NSAIDs (like Indomethacin) can also be used in NDI as they reduce renal blood flow and inhibit the antagonistic effect of prostaglandins on ADH. * **Side Effects of Thiazides:** Remember the "Hypo" triad: Hypokalemia, Hyponatremia, and Hypomagnesemia; and the "Hyper" triad: Hypercalcemia, Hyperuricemia, and Hyperglycemia.

Q: Which of the following is NOT a potassium-sparing diuretic?

Ethacrynic acid. ### Explanation The correct answer is **D. Ethacrynic acid**. **1. Why Ethacrynic acid is the correct answer:** Ethacrynic acid is a **Loop Diuretic**, not a potassium-sparing one. It works by inhibiting the **Na⁺/K⁺/2Cl⁻ symporter** in the Thick Ascending Limb (TAL) of the Loop of Henle. Because it causes a massive delivery of sodium to the distal tubule, it increases potassium secretion into the urine, leading to **hypokalemia** (low potassium). It is chemically unique among loop diuretics because it is a phenoxyacetic acid derivative and **not a sulfonamide**, making it the drug of choice for patients with sulfa allergies. **2. Why the other options are incorrect:** * **A. Spironolactone:** This is a competitive **Aldosterone Antagonist** (Mineralocorticoid receptor antagonist). By blocking aldosterone in the collecting duct, it prevents the reabsorption of Na⁺ and the secretion of K⁺, thus "sparing" potassium. * **B. Triamterene & C. Amiloride:** These are **Direct ENaC (Epithelial Sodium Channel) Blockers**. They act on the late distal tubule and collecting duct to block sodium entry independently of aldosterone. By decreasing the negative intraluminal potential, they reduce the driving force for potassium secretion. **3. High-Yield Clinical Pearls for NEET-PG:** * **Ototoxicity:** Ethacrynic acid is the **most ototoxic** loop diuretic; it is more likely to cause permanent hearing loss compared to Furosemide. * **Liddle’s Syndrome:** Amiloride is the treatment of choice for this rare genetic condition. * **Spironolactone Side Effects:** Can cause **gynecomastia** and impotence due to its non-specific binding to androgen and progesterone receptors. **Eplerenone** is a more specific alternative with fewer hormonal side effects. * **Potassium-sparing diuretics** are often combined with Thiazides or Loop diuretics to counteract drug-induced hypokalemia.

Q: Tolvaptan is approved for use in which of the following conditions?

Hyponatremia. **Explanation:** **Tolvaptan** is a selective, oral **V2-receptor antagonist** (Vaptan). It works by blocking the action of Antidiuretic Hormone (ADH/Vasopressin) at the V2 receptors in the collecting ducts of the kidney. This leads to **aquaresis**—the excretion of free water without significant loss of electrolytes like sodium or potassium. **Why Hyponatremia is Correct:** By promoting free water clearance, Tolvaptan increases the concentration of serum sodium. It is specifically FDA-approved for the treatment of **euvolemic and hypervolemic hyponatremia**, such as that seen in **SIADH** (Syndrome of Inappropriate ADH secretion), Cirrhosis, or Heart Failure. **Why Other Options are Incorrect:** * **A. Hypernatremia:** Tolvaptan increases serum sodium levels; using it in hypernatremia would dangerously worsen the condition. * **B. Hyperkalemia:** Tolvaptan does not significantly affect potassium excretion. Hyperkalemia is typically managed with Loop diuretics, insulin/dextrose, or potassium binders. * **C. Hypercalcemia:** Loop diuretics (like Furosemide) are used to treat hypercalcemia by increasing calcium excretion. Tolvaptan has no role in calcium homeostasis. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Selective V2 antagonist (Aquaretic). * **Other Indications:** Also approved to slow the progression of **Autosomal Dominant Polycystic Kidney Disease (ADPKD)**. * **Contraindication:** Should not be used for more than 30 days due to the risk of **hepatotoxicity**. * **Caution:** Rapid correction of hyponatremia must be avoided to prevent **Osmotic Demyelination Syndrome (Central Pontine Myelinolysis)**. * **Conivaptan** is a related drug but differs as it is a non-selective (V1a and V2) antagonist and is administered intravenously.

Q: Acetazolamide can be used in all the following conditions except:

Cirrhosis. **Explanation:** **Acetazolamide** is a Carbonic Anhydrase (CA) inhibitor that acts primarily on the proximal convoluted tubule. **Why Cirrhosis is the Correct Answer (Contraindication):** In patients with cirrhosis, the liver cannot efficiently convert ammonia ($NH_3$) into urea. Acetazolamide alkalinizes the urine by increasing bicarbonate excretion. In an alkaline urinary environment, ammonium ions ($NH_4^+$) are converted back into lipid-soluble ammonia ($NH_3$), which is reabsorbed into the systemic circulation. This elevation in blood ammonia levels can cross the blood-brain barrier, precipitating or worsening **Hepatic Encephalopathy**. Therefore, it is strictly contraindicated in liver cirrhosis. **Why other options are incorrect (Indications):** * **Epilepsy:** Acetazolamide creates a mild metabolic acidosis in the CNS, which increases the seizure threshold. It is used as an adjuvant in absence and tonic-clonic seizures. * **Acute Mountain Sickness:** It counteracts respiratory alkalosis by increasing bicarbonate excretion, thereby lowering blood pH. This stimulates the respiratory center to increase ventilation and improves oxygenation. * **Glaucoma:** By inhibiting CA in the ciliary body, it reduces the formation of aqueous humor, thereby lowering intraocular pressure. **High-Yield Clinical Pearls for NEET-PG:** * **Site of Action:** Proximal Convoluted Tubule (PCT). * **Side Effects:** Hyperchloremic metabolic acidosis, hypokalemia, paresthesia, and renal stones (due to calcium phosphate precipitation in alkaline urine). * **Other Uses:** Idiopathic Intracranial Hypertension (Pseudotumor cerebri) and urinary alkalinization (to excrete acidic drugs like uric acid or cystine). * **Sulfa-Allergy:** As a sulfonamide derivative, it may cause cross-reactivity in sensitive patients.

Q: Which of the following diuretics acts at the nephron's distal tubule?

Hydrochlorothiazide. **Explanation:** The correct answer is **Hydrochlorothiazide (C)**. **Mechanism and Site of Action:** Hydrochlorothiazide belongs to the **Thiazide** class of diuretics. These agents act specifically on the **early distal convoluted tubule (DCT)** [1]. They work by inhibiting the **Na⁺-Cl⁻ symporter** on the luminal membrane [2]. By blocking this transporter, they increase the excretion of sodium and chloride, followed by water. Because the DCT is responsible for only about 5–10% of sodium reabsorption, thiazides are considered "medium-efficacy" diuretics [4]. **Analysis of Incorrect Options:** * **A & B (Ethacrynic acid and Furosemide):** These are **Loop Diuretics**. They act on the **thick ascending limb (TAL) of the Loop of Henle** by inhibiting the Na⁺-K⁺-2Cl⁻ cotransporter [2]. They are "high-ceiling" diuretics used for acute pulmonary edema and refractory hypertension. * **D (Mannitol):** This is an **Osmotic Diuretic**. Its primary site of action is the **Proximal Convoluted Tubule (PCT)** and the descending limb of the Loop of Henle [3]. It works by increasing the osmolarity of the tubular fluid, preventing water reabsorption. **NEET-PG High-Yield Pearls:** * **Calcium Paradox:** Unlike Loop diuretics (which cause hypocalcemia), Thiazides **decrease urinary calcium excretion** (hypercalcemia) [1]. This makes them the drug of choice for hypertension in patients with **osteoporosis** or recurrent **calcium oxalate stones**. * **Metabolic Side Effects:** Remember the "4 Hypers and 2 Hypos": **Hyper**uricemia (gout), **Hyper**glycemia, **Hyper**lipidemia, **Hyper**calcemia; and **Hypo**kalemia, **Hypo**natremia [1]. * **Sulfa Allergy:** Most thiazides and loop diuretics (except Ethacrynic acid) are sulfonamide derivatives [2].

Q: Which of the following drugs does not require its presence in the tubular lumen for diuretic action?

Eplerenone. ### Explanation The correct answer is **D. Eplerenone**. #### 1. Why Eplerenone is Correct Most diuretics function by inhibiting transporters or enzymes located on the **luminal (apical) membrane** of the renal tubule. To reach these targets, they must be filtered or secreted into the tubular fluid. **Eplerenone** (and Spironolactone) are **Mineralocorticoid Receptor Antagonists (MRAs)**. Their target receptors are located in the **cytosol** of the principal cells in the late distal tubule and collecting duct. These drugs reach their target by diffusing directly from the **peritubular capillaries (blood side)** across the basolateral membrane into the cell. Therefore, their presence in the tubular lumen is not required for their pharmacological action. #### 2. Why Other Options are Incorrect * **Chlorthalidone (Thiazide-like):** Must be secreted into the lumen via the organic acid secretory pathway to inhibit the Na⁺/Cl⁻ symporter on the luminal membrane of the distal convoluted tubule. * **Acetazolamide (Carbonic Anhydrase Inhibitor):** Acts primarily on luminal carbonic anhydrase (Type IV) in the proximal convoluted tubule; it requires luminal presence to function. * **Mannitol (Osmotic Diuretic):** Works by increasing the osmolarity of the **tubular fluid**, thereby retaining water in the lumen. It must be filtered into the lumen to exert its effect. #### 3. NEET-PG High-Yield Pearls * **Site of Action:** MRAs are the only diuretics that do not act from the luminal side. * **Clinical Advantage:** Because they don't rely on tubular secretion, MRAs remain effective even in states of reduced renal perfusion where organic acid transporters are compromised. * **Side Effects:** Eplerenone is more selective than Spironolactone, causing significantly fewer endocrine side effects like gynecomastia or impotence. * **Key Contraindication:** Avoid in patients with hyperkalemia (K⁺ > 5.5 mEq/L) or severe renal impairment.

Question 1

Mannitol produces diuresis by which mechanism?

Accepted Answer

Osmotic effect

Answer

Inhibition of Na-K-2Cl cotransporter

Answer

Inhibition of Na-K ATPase

Answer

Inhibition of aquaporin channels

Question 2

Which diuretic causes gynecomastia?

Accepted Answer

Spironolactone

Answer

Lubiprostone

Answer

Cimetidine

Answer

Chlorthalidone

Question 3

Which of the following drugs is used in the management of nephrogenic diabetes insipidus?

Accepted Answer

Thiazides

Answer

Mannitol

Answer

Spironolactone

Answer

Demeclocycline

Question 4

Which of the following is NOT a potassium-sparing diuretic?

Accepted Answer

Ethacrynic acid

Answer

Spironolactone

Answer

Triamterene

Answer

Amiloride

Question 5

All of the following diuretics act from the luminal side of the renal tubules except?

Accepted Answer

Aldosterone antagonists

Answer

Loop diuretics

Answer

ENaC blockers

Answer

Mannitol

Question 6

Tolvaptan is approved for use in which of the following conditions?

Accepted Answer

Hyponatremia

Answer

Hypernatremia

Answer

Hyperkalemia

Answer

Hypercalcemia

Question 7

NSAIDs attenuate the action of which of the following diuretics?

Accepted Answer

Loop diuretics

Answer

Carbonic anhydrase inhibitors

Answer

Thiazide diuretics

Answer

Spironolactone

Question 8

Acetazolamide can be used in all the following conditions except:

Accepted Answer

Cirrhosis

Answer

Epilepsy

Answer

Acute mountain sickness

Answer

Glaucoma

Question 9

Which of the following diuretics acts at the nephron's distal tubule?

Accepted Answer

Hydrochlorothiazide

Answer

Ethacrynic acid

Answer

Furosemide

Answer

Mannitol

Question 10

Which of the following drugs does not require its presence in the tubular lumen for diuretic action?

Accepted Answer

Eplerenone

Answer

Chlorthalidone

Answer

Acetazolamide

Answer

Mannitol

Diuretics — MCQs

Diuretics — MCQs

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