Diuretics — MCQs

Diuretics Indian Medical PG Practice Questions and MCQs

Question 121: Which of the following diuretics acts at the nephron's distal tubule?

A. Ethacrynic acid
B. Furosemide
C. Hydrochlorothiazide (Correct Answer)
D. Mannitol

Explanation: **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].

Question 122: Which of the following drugs does not require its presence in the tubular lumen for diuretic action?

A. Chlorthalidone
B. Acetazolamide
C. Mannitol
D. Eplerenone (Correct Answer)

Explanation: ### 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 123: All of the following are true about loop diuretics except:

A. They are called "high ceiling" diuretics.
B. They act on the Na+, K+, 2Cl- symporter.
C. They can cause hyperuricemia.
D. Loop diuretics lead to hypercalcemia and hypomagnesemia. (Correct Answer)

Explanation: **Explanation:** The correct answer is **D** because loop diuretics (e.g., Furosemide) actually cause **hypocalcemia**, not hypercalcemia. **1. Why Option D is the correct (false) statement:** Loop diuretics inhibit the **Na⁺-K⁺-2Cl⁻ symporter** in the Thick Ascending Limb (TAL) of the Loop of Henle. Normally, the "back-leak" of potassium into the lumen creates a positive luminal potential that drives the paracellular reabsorption of divalent cations like **Calcium (Ca²⁺)** and **Magnesium (Mg²⁺)**. By blocking this transporter, loop diuretics abolish this electrical gradient, leading to increased urinary excretion of both Calcium and Magnesium. Thus, they cause **hypocalcemia** and **hypomagnesemia**. **2. Why other options are incorrect (true statements):** * **Option A:** They are "high ceiling" diuretics because they have a very high maximal efficacy; as the dose increases, the diuretic effect continues to rise significantly compared to other classes. * **Option B:** Their primary mechanism of action is the reversible inhibition of the **NKCC2** (Na⁺-K⁺-2Cl⁻) symporter in the TAL. * **Option C:** They cause **hyperuricemia** by competing with uric acid for the organic acid secretory pump in the proximal tubule and by increasing proximal reabsorption due to volume depletion. **NEET-PG High-Yield Pearls:** * **Mnemonic for Calcium:** **L**oops **L**ose Calcium (Hypocalcemia); **T**hiazides **T**ake Calcium (Hypercalcemia). * **Drug of Choice:** Furosemide is the drug of choice for **Acute Pulmonary Edema**. * **Ototoxicity:** Loop diuretics (especially Ethacrynic acid) can cause dose-dependent hearing loss. * **Metabolic Effect:** They typically cause **Hypokalemic Metabolic Alkalosis**.

Question 124: Hypercalcemia is caused by all of the following except:

A. Thyrotoxicosis
B. Vitamin D intoxication
C. Sarcoidosis
D. Furosemide (Correct Answer)

Explanation: ### Explanation The correct answer is **D. Furosemide**. **1. Why Furosemide is the Correct Answer:** Furosemide is a **Loop Diuretic** that inhibits the $Na^+-K^+-2Cl^-$ symporter in the Thick Ascending Limb (TAL) of the Henle’s loop. This inhibition abolishes the positive transepithelial potential usually generated by the back-diffusion of potassium. Without this positive charge, the paracellular reabsorption of divalent cations ($Ca^{2+}$ and $Mg^{2+}$) is blocked, leading to increased urinary calcium excretion (**Hypercalciuria**). Consequently, Furosemide causes **hypocalcemia**, not hypercalcemia, and is clinically used in the emergency management of severe hypercalcemia. **2. Analysis of Incorrect Options:** * **Thyrotoxicosis:** Excess thyroid hormone increases bone turnover by stimulating osteoclastic activity, leading to the release of calcium into the bloodstream. * **Vitamin D Intoxication:** Vitamin D increases calcium absorption from the GI tract and enhances bone resorption, directly causing hypercalcemia. * **Sarcoidosis:** This granulomatous disease involves macrophages that contain 1-alpha-hydroxylase, which converts Vitamin D into its active form ($1,25-(OH)_2D_3$), leading to hypercalcemia. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic:** *"Loop Loses Calcium, Thiazide Takes Calcium."* * **Thiazides:** Unlike loops, Thiazides cause **hypercalcemia** (by increasing proximal tubule reabsorption and distal tubular $Ca^{2+}$ exchange). They are used to treat idiopathic hypercalciuria/renal stones. * **Loop Diuretics:** Cause **Hypomagnesemia** and **Hypocalcemia**. Furosemide is the drug of choice for acute hypercalcemia (given with saline to prevent volume depletion). * **Milk-Alkali Syndrome:** Another classic cause of hypercalcemia due to excessive intake of calcium carbonate antacids.

Question 125: Which drug is a vasopressin V2 receptor selective agonist?

A. Lypressin
B. Desmopressin (Correct Answer)
C. Terlipressin
D. None of the above

Explanation: **Explanation:** The correct answer is **Desmopressin**. **1. Why Desmopressin is correct:** Vasopressin (ADH) acts on two primary receptors: **V1** (located on vascular smooth muscle, causing vasoconstriction) and **V2** (located in the renal collecting ducts, causing water reabsorption via aquaporin-2 channels). **Desmopressin (dDAVP)** is a synthetic analogue of vasopressin designed to be a **selective V2 receptor agonist**. It has negligible V1 activity, meaning it provides potent antidiuretic effects without causing significant hypertension or vasoconstriction. It also has a longer duration of action than natural vasopressin. **2. Why the other options are incorrect:** * **Lypressin:** This is a synthetic version of lysine-vasopressin. While it acts on both V1 and V2 receptors, it is not selective for V2 and is rarely used in modern practice due to its short half-life. * **Terlipressin:** This is a prodrug of lysine-vasopressin that is highly **V1-selective**. Because it causes potent vasoconstriction, it is the drug of choice for managing bleeding esophageal varices and hepatorenal syndrome, rather than for its antidiuretic effects. **3. NEET-PG High-Yield Pearls:** * **Clinical Uses of Desmopressin:** Central Diabetes Insipidus (drug of choice), Nocturnal Enuresis, von Willebrand Disease (Type 1), and Hemophilia A (it increases levels of Factor VIII and vWF). * **Route of Administration:** Desmopressin is commonly administered intranasally, orally, or parenterally. * **Adverse Effect:** The most serious side effect of Desmopressin is **dilutional hyponatremia**, which can lead to seizures. * **V3 Receptors:** These are located in the anterior pituitary and mediate the release of ACTH.

Question 126: Which of the following diuretics is contraindicated in the presence of cardiac failure?

A. Mannitol (Correct Answer)
B. Spironolactone
C. Furosemide
D. Hydrochlorothiazide

Explanation: ### Explanation **Correct Option: A. Mannitol** Mannitol is an **osmotic diuretic**. When administered intravenously, it remains in the extracellular fluid (ECF) and creates a high osmotic pressure. This causes a rapid shift of water from the intracellular compartment into the vascular space. In patients with pre-existing **congestive heart failure (CHF)**, this sudden increase in intravascular volume (acute volume expansion) can overload the heart, leading to **acute pulmonary edema**. Therefore, it is strictly contraindicated in patients with cardiac failure or pulmonary congestion. **Why the other options are incorrect:** * **B. Spironolactone:** This is a potassium-sparing diuretic (aldosterone antagonist). It is actually **indicated** in chronic heart failure (NYHA Class II-IV) as it reduces cardiac remodeling and decreases mortality (as proven in the RALES trial). * **C. Furosemide:** This is a loop diuretic and the **drug of choice** for acute pulmonary edema secondary to heart failure. It rapidly reduces preload through both venodilation and potent diuresis. * **D. Hydrochlorothiazide:** Thiazide diuretics are commonly used to manage fluid overload in mild heart failure and are first-line agents for hypertension. **Clinical Pearls for NEET-PG:** * **Indications for Mannitol:** Increased intracranial pressure (cerebral edema) and increased intraocular pressure (acute glaucoma). * **Test-taking Tip:** If a question asks for a diuretic that *causes* pulmonary edema, think Mannitol. If it asks for the drug to *treat* pulmonary edema, think Furosemide. * **Contraindications for Mannitol:** Active intracranial bleeding (except during craniotomy), severe dehydration, and established renal failure (anuria).

Question 127: Which one of the following is an aldosterone antagonist?

A. Spironolactone (Correct Answer)
B. Amiloride
C. Triamterene
D. Acetazolamide

Explanation: **Explanation:** The correct answer is **Spironolactone**. **1. Why Spironolactone is correct:** Spironolactone is a **competitive aldosterone antagonist**. It acts on the mineralocorticoid receptors in the late distal tubule and collecting duct. By blocking these receptors, it prevents the synthesis of aldosterone-induced proteins (AIPs), leading to decreased sodium reabsorption and decreased potassium secretion. It is classified as a **Potassium-Sparing Diuretic**. **2. Why the other options are incorrect:** * **Amiloride & Triamterene:** While these are also potassium-sparing diuretics, they are **not** aldosterone antagonists. Instead, they act as **direct ENaC (Epithelial Sodium Channel) blockers** in the luminal membrane of the collecting duct. They work independently of aldosterone levels. * **Acetazolamide:** This is a **Carbonic Anhydrase inhibitor** that acts primarily on the proximal convoluted tubule (PCT). It is used for glaucoma and altitude sickness, not for its aldosterone-modulating effects. **3. NEET-PG High-Yield Clinical Pearls:** * **Side Effects:** Spironolactone can cause **gynecomastia** and impotence in men because it also blocks androgen receptors. **Eplerenone** is a more selective aldosterone antagonist with fewer anti-androgenic side effects. * **Clinical Use:** Spironolactone is the drug of choice for **Primary Hyperaldosteronism (Conn’s Syndrome)** and is proven to reduce mortality in **Congestive Heart Failure (NYHA Class II-IV)**. * **Contraindication:** All potassium-sparing diuretics are contraindicated in patients with **hyperkalemia** or chronic renal failure.

Question 128: Brinzolamide is a

A. Highly specific irreversible and noncompetitive carbonic anhydrase inhibitor
B. Highly specific irreversible and competitive carbonic anhydrase inhibitor.
C. Highly specific reversible and competitive carbonic anhydrase inhibitor
D. Highly specific reversible and non-competitive carbonic anhydrase inhibitor. (Correct Answer)

Explanation: **Explanation:** **Brinzolamide** is a topical carbonic anhydrase inhibitor (CAI) primarily used to reduce intraocular pressure in open-angle glaucoma and ocular hypertension. **1. Why Option D is correct:** Carbonic anhydrase inhibitors like Brinzolamide and Dorzolamide work by binding to the **CA-II isoenzyme** in the ciliary processes of the eye. * **Highly Specific:** It has a high affinity for the CA-II isoform, which is the most active form involved in aqueous humor production. * **Reversible:** The binding is not permanent; the drug eventually dissociates from the enzyme. * **Non-competitive:** Brinzolamide binds to a site on the enzyme that is distinct from the substrate-binding site (the active site where $CO_2$ and $H_2O$ react). Therefore, it inhibits the enzyme regardless of the substrate concentration. **2. Why other options are incorrect:** * **Options A & B (Irreversible):** Most clinically used diuretics and CAIs bind reversibly. Irreversible binding would lead to prolonged enzyme inactivation until new enzymes are synthesized, which is not the pharmacokinetic profile of Brinzolamide. * **Option C (Competitive):** Competitive inhibitors compete with the substrate for the active site. Brinzolamide’s mechanism involves non-competitive inhibition, ensuring potent suppression of aqueous humor formation even when substrate levels vary. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Inhibits CA-II $\rightarrow$ Decreased $HCO_3^-$ production $\rightarrow$ Decreased aqueous humor secretion $\rightarrow$ Lower Intraocular Pressure (IOP). * **Advantage over Dorzolamide:** Brinzolamide is a suspension with a physiological pH, making it **less irritating** (less stinging/burning) than Dorzolamide. * **Systemic CAIs:** Acetazolamide is the prototype oral CAI, often used for altitude sickness and glaucoma, but carries a risk of metabolic acidosis and hypokalemia. * **Side Effect:** A common side effect of topical CAIs is a **bitter taste** (dysgeusia) due to the drug draining through the nasolacrimal duct.

Question 129: All of the following are true regarding diuretics except?

A. Spironolactone is a potassium sparing drug.
B. Mannitol is an osmotic diuretic.
C. Thiazides act by inhibiting sodium-chloride co-transporter. (Correct Answer)
D. Acetazolamide inhibits carbonic anhydrase enzyme.

Explanation: **Explanation** This question requires identifying the incorrect statement regarding the mechanism of action of various diuretics. However, based on pharmacological principles, **all four statements provided are actually correct.** In the context of NEET-PG, if this question appeared as written, it would be considered a "disputed" or "bonus" question. 1. **Why Option C is technically correct (but listed as the answer):** Thiazide diuretics (e.g., Hydrochlorothiazide) act specifically on the **Distal Convoluted Tubule (DCT)** by inhibiting the **$Na^+-Cl^-$ symporter** (co-transporter). This increases the excretion of sodium and chloride. If this was intended as the "incorrect" answer, it may be due to a typographical error in the question stem or options. 2. **Analysis of other options:** * **Option A:** **Spironolactone** is indeed a potassium-sparing diuretic. It acts as an **Aldosterone antagonist** in the collecting duct, preventing sodium reabsorption and potassium secretion. * **Option B:** **Mannitol** is a classic **osmotic diuretic**. It works by increasing the osmolarity of tubular fluid, primarily in the Proximal Convoluted Tubule and the Descending Loop of Henle, preventing water reabsorption. * **Option D:** **Acetazolamide** is a **Carbonic Anhydrase inhibitor**. It acts in the PCT to prevent $NaHCO_3$ reabsorption, leading to alkaline diuresis. **High-Yield Clinical Pearls for NEET-PG:** * **Site of Action:** Carbonic Anhydrase Inhibitors (PCT); Loop Diuretics (Thick Ascending Limb); Thiazides (DCT); K-Sparing (Collecting Duct). * **Loop Diuretics (Furosemide):** Inhibit $Na^+-K^+-2Cl^-$ co-transporter; cause hypokalemia and **hypocalcemia**. * **Thiazides:** Can cause hypokalemia but lead to **hypercalcemia** (useful in post-menopausal osteoporosis). * **Drug of Choice:** Acetazolamide is the DOC for Glaucoma and Mountain Sickness; Spironolactone is the DOC for Cirrhotic Ascites.

Question 130: A 52-year-old male presents with a chief complaint of a substantial increase in breast size over the past few months. Three months ago, he was diagnosed with hypertension and placed on antihypertensive medication. Which of the following medications was most likely prescribed?

A. Captopril
B. Furosemide
C. Hydrochlorothiazide
D. Spironolactone (Correct Answer)

Explanation: ### Explanation **Correct Answer: D. Spironolactone** **Mechanism & Rationale:** The clinical presentation describes **gynecomastia** (enlargement of male breast tissue), a well-known side effect of **Spironolactone**. Spironolactone is a potassium-sparing diuretic that acts as a competitive antagonist at the mineralocorticoid receptor. However, it lacks specificity and also acts as an **anti-androgen**. It causes gynecomastia through three primary mechanisms: 1. Displacing dihydrotestosterone (DHT) from androgen receptors. 2. Increasing the peripheral conversion of testosterone to estradiol. 3. Increasing the metabolic clearance of testosterone. **Analysis of Incorrect Options:** * **A. Captopril:** An ACE inhibitor. While it can cause a dry cough or angioedema, it is not typically associated with gynecomastia. * **B. Furosemide:** A loop diuretic used for edema and heart failure. Its primary side effects include ototoxicity, hypokalemia, and hyperuricemia, but not endocrine disturbances like gynecomastia. * **C. Hydrochlorothiazide:** A thiazide diuretic. Common side effects include hyperglycemia, hyperlipidemia, and hyperuricemia. While it can occasionally cause erectile dysfunction, it does not cause breast enlargement. **High-Yield Clinical Pearls for NEET-PG:** * **Eplerenone** is a selective aldosterone antagonist that does *not* cause gynecomastia, making it the preferred alternative if this side effect occurs. * **Mnemonic for drugs causing Gynecomastia (DISCO):** **D**igoxin, **I**soniazid, **S**pironolactone, **C**imetidine, **O**estrogens/Ketoconazole. * Spironolactone is the drug of choice for **Primary Hyperaldosteronism (Conn’s Syndrome)** and is used to improve survival in Congestive Heart Failure (NYHA Class II-IV).

Practice by Chapter

Carbonic Anhydrase Inhibitors

Practice Questions

Loop Diuretics

Practice Questions

Thiazide and Thiazide-Like Diuretics

Practice Questions

Potassium-Sparing Diuretics

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Carbonic Anhydrase Inhibitors

Practice Questions

Osmotic Diuretics

Practice Questions

Combination Diuretic Therapy

Practice Questions

Diuretics in Heart Failure

Practice Questions

Diuretics in Hypertension

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Diuretics in Renal Disorders

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Adverse Effects and Drug Interactions

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Diuretics — MCQs

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