Diuretics Practice Questions

Q: What is the active metabolite of spironolactone?

Canrenone. **Explanation:** **Spironolactone** is a synthetic steroid that acts as a competitive antagonist of the mineralocorticoid receptor (Aldosterone antagonist). It is a **prodrug** with a relatively short half-life (approx. 1.5 hours). Its clinical efficacy is primarily attributed to its conversion in the liver into active metabolites, the most significant being **Canrenone**. Canrenone has a much longer half-life (approx. 16.5 hours), which accounts for the prolonged duration of action of spironolactone. **Analysis of Options:** * **A. Gluconalactone:** This is an unrelated polyhydroxy acid used in skincare and food chemistry; it has no role in diuretic pharmacology. * **B. Eplerenone:** This is a separate, more selective mineralocorticoid receptor antagonist. It is not a metabolite of spironolactone but is often preferred clinically because it does not cause gynecomastia. * **D. Triamterene:** This is a direct ENaC (epithelial sodium channel) blocker. While it is also a potassium-sparing diuretic, it works via a different mechanism and is not chemically related to spironolactone. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Acts on the late distal tubule and collecting duct to inhibit $Na^+/K^+$ exchange. * **Side Effects:** Due to its steroid structure, it also antagonizes androgen receptors, leading to **gynecomastia**, impotence, and menstrual irregularities. * **Drug of Choice:** It is the diuretic of choice for **Cirrhosis with Ascites** and **Primary Hyperaldosteronism (Conn’s Syndrome)**. * **Mortality Benefit:** Proven to reduce mortality in Chronic Heart Failure (NYHA Class II-IV).

Q: Hyperuricemia is seen with which of the following drugs?

Chlorthiazide. **Explanation:** **Chlorthiazide** (a Thiazide diuretic) causes hyperuricemia primarily through two mechanisms: 1. **Competition for Secretion:** Thiazides are organic acids that compete with uric acid for the Organic Anion Transporter (OAT) in the proximal convoluted tubule, reducing uric acid secretion into the tubular lumen. 2. **Enhanced Reabsorption:** Diuretic-induced hypovolemia triggers the proximal tubule to increase the reabsorption of sodium and water, which leads to a compensatory increase in the reabsorption of uric acid. **Analysis of Incorrect Options:** * **Acetazolamide (Carbonic Anhydrase Inhibitor):** While it acts on the proximal tubule, it actually increases the excretion of uric acid (uricosuric effect) by inhibiting its reabsorption. * **Mannitol (Osmotic Diuretic):** It acts by increasing the osmolarity of the tubular fluid. It does not significantly interfere with the organic acid transport system and does not typically cause hyperuricemia. * **Triamterene (K+-Sparing Diuretic):** It acts on the late distal tubule and collecting duct by blocking ENaC channels. It does not affect the proximal tubule’s uric acid transport mechanisms. **NEET-PG High-Yield Pearls:** * **The "Hyper" Rule for Thiazides:** Thiazides cause **Hyper**uricemia, **Hyper**glycemia, **Hyper**lipidemia, and **Hyper**calcemia (unlike Loop diuretics, which cause *hypo*calcemia). * **Loop Diuretics (e.g., Furosemide):** These also cause hyperuricemia via similar mechanisms (competition at OAT and volume depletion). * **Clinical Contraindication:** Thiazides and Loop diuretics should be used with caution in patients with a history of **Gout**, as they can precipitate an acute attack.

Q: Which drug abolishes the corticomedullary osmotic gradient?

Furosemide. ### Explanation **Correct Option: A. Furosemide** The **corticomedullary osmotic gradient** is the increasing osmolality of the renal interstitium from the cortex (300 mOsm/L) to the deep medulla (1200 mOsm/L). This gradient is primarily established and maintained by the **Countercurrent Multiplier system** in the Thick Ascending Limb (TAL) of the Loop of Henle. Furosemide (a loop diuretic) inhibits the **Na⁺-K⁺-2Cl⁻ (NKCC2) symporter** in the TAL. By blocking the reabsorption of these electrolytes into the medullary interstitium, it prevents the buildup of high osmotic pressure in the medulla. Consequently, the gradient is "abolished" or washed out. Without this gradient, the collecting duct cannot reabsorb water even in the presence of ADH, leading to the excretion of large volumes of dilute urine. **Why Incorrect Options are Wrong:** * **B. Thiazides:** These act on the **Distal Convoluted Tubule (DCT)**. Since the DCT is located entirely within the renal cortex and does not participate in the countercurrent multiplier system, thiazides do not affect the medullary osmotic gradient. * **C & D. Spironolactone and Triamterene:** These are **Potassium-sparing diuretics** acting on the late distal tubule and collecting ducts. Their site of action is beyond the segment responsible for generating the medullary gradient. **High-Yield NEET-PG Pearls:** * **Loop Diuretics** are the most potent diuretics ("High-ceiling") because the TAL reabsorbs ~25% of filtered sodium. * Because they abolish the gradient, loop diuretics impair the kidney's ability to both **concentrate** urine (during dehydration) and **dilute** urine. * **Clinical Correlation:** Loop diuretics are the drugs of choice for acute pulmonary edema and generalized edema (CHF, Nephrotic syndrome). * **Side Effects:** Hypokalemia, Hyperuricemia, Ototoxicity, and Hypocalcemia ("Loops Lose Calcium").

Q: Which of the following diuretics acts on the nephron through the interstitium?

Spironolactone. ### Explanation **Correct Option: D (Spironolactone)** The fundamental concept here is the **site of action** and the **route of access** to the receptor. Most diuretics (Thiazides, Loop diuretics, Carbonic anhydrase inhibitors) act from the **luminal side** of the nephron. They must be filtered at the glomerulus or secreted into the tubular fluid to reach their target transporters. **Spironolactone**, however, is a competitive **Aldosterone Antagonist**. Aldosterone receptors (Mineralocorticoid Receptors) are located in the **cytoplasm** of the principal cells in the late distal tubule and collecting duct. Spironolactone reaches these receptors by diffusing from the **peritubular capillaries through the interstitium** into the basolateral side of the cell. It does not need to be present in the tubular lumen to exert its effect. **Analysis of Incorrect Options:** * **A. Thiazides:** Act on the $Na^+/Cl^-$ symporter in the Distal Convoluted Tubule (DCT) from the **luminal side**. * **B. Furosemide:** A loop diuretic that inhibits the $Na^+/K^+/2Cl^-$ cotransporter in the Thick Ascending Limb (TAL). It is highly protein-bound and reaches the **lumen** via organic acid secretory pumps in the proximal tubule. * **C. Acetazolamide:** Inhibits Carbonic Anhydrase primarily at the **luminal brush border** of the Proximal Convoluted Tubule (PCT). **High-Yield NEET-PG Pearls:** * **Potassium Sparing:** Spironolactone is the drug of choice for **Primary Hyperaldosteronism (Conn’s Syndrome)** and edema associated with **Liver Cirrhosis**. * **Side Effects:** Due to its steroid structure, it can cause **Gynecomastia** and impotence in males (anti-androgenic effect). **Eplerenone** is a more selective alternative with fewer endocrine side effects. * **Clinical Marker:** It is proven to reduce mortality in patients with **Chronic Heart Failure** (NYHA Class II-IV).

Q: What is the mechanism of action of bumetanide?

Loop diuretic. **Explanation:** **Bumetanide** is a potent **Loop Diuretic** (High-ceiling diuretic). Its primary mechanism of action involves the reversible inhibition of the **Na⁺-K⁺-2Cl⁻ symporter (NKCC2)** located in the **thick ascending limb (TAL)** of the Loop of Henle. By blocking this transporter, it prevents the reabsorption of sodium, potassium, and chloride, leading to significant natriuresis and diuresis. It is approximately 40 times more potent than furosemide. **Analysis of Incorrect Options:** * **Option A (ACE Inhibitors):** Drugs like Enalapril or Lisinopril inhibit the conversion of Angiotensin I to Angiotensin II; they are antihypertensives, not diuretics. * **Option B (Carbonic Anhydrase Inhibitors):** Drugs like Acetazolamide act on the proximal convoluted tubule. They are much weaker diuretics and are primarily used for glaucoma or altitude sickness. * **Option D (Potassium-sparing Diuretics):** Drugs like Spironolactone (aldosterone antagonist) or Amiloride (ENaC blocker) act on the distal tubule and collecting duct. Unlike loop diuretics, they prevent potassium loss. **High-Yield Clinical Pearls for NEET-PG:** * **Site of Action:** Thick Ascending Limb (TAL) of the Loop of Henle. * **Metabolic Effects:** Loop diuretics cause **"Hypo-everything"** (Hypokalemia, Hyponatremia, Hypomagnesemia, Hypocalcemia) except for **Hyperuricemia** and **Hyperglycemia**. * **Drug of Choice:** Loop diuretics are the preferred agents for acute pulmonary edema and symptomatic heart failure. * **Ototoxicity:** While all loop diuretics can cause ototoxicity, ethacrynic acid is the most ototoxic; bumetanide is generally considered to have a lower risk compared to high-dose furosemide.

Question 1

What is the active metabolite of spironolactone?

Accepted Answer

Canrenone

Answer

Gluconalactone

Answer

Eplerenone

Answer

Triamterene

Question 2

Hyperuricemia is seen with which of the following drugs?

Accepted Answer

Chlorthiazide

Answer

Acetazolamide

Answer

Mannitol

Answer

Triamterene

Question 3

Which of the following adverse effects is associated with thiazide diuretics?

Accepted Answer

Impotence

Answer

Hyperkalemic paralysis

Answer

Hypouricemia

Answer

Hypolipidemia

Question 4

Which drug abolishes the corticomedullary osmotic gradient?

Accepted Answer

Furosemide

Answer

Thiazide

Answer

Spironolactone

Answer

Triamterene

Question 5

Indomethacin can antagonize the diuretic action of loop diuretics by which mechanism?

Accepted Answer

Preventing prostaglandin-mediated intrarenal-hemodynamic actions

Answer

Blocking the action in the ascending limb of the loop of Henle

Answer

Enhancing salt and water reabsorption in distal tubules

Answer

Increasing aldosterone secretion

Question 6

All of the following are true about osmotic diuretics except:

Accepted Answer

Osmotic diuretics are used in active cerebral bleeding.

Answer

They expand the extracellular fluid compartment and increase renal blood flow.

Answer

Osmotic diuretics are used in cerebral edema.

Answer

Mannitol is used in acute congestive glaucoma.

Question 7

In patients with decompensated cirrhosis on diuretic therapy presenting with tender gynecomastia, which diuretic is the best substitution?

Accepted Answer

Amiloride to substitute spironolactone

Answer

Furosemide to substitute spironolactone

Answer

Spironolactone to substitute amiloride

Answer

Torsemide to substitute spironolactone

Question 8

Which of the following diuretics acts on the nephron through the interstitium?

Accepted Answer

Spironolactone

Answer

Thiazide

Answer

Furosemide

Answer

Acetazolamide

Question 9

What is true about triamterene?

Accepted Answer

Its saluretic effect is greater than that of thiazides.

Answer

It is often combined with thiazide diuretics.

Answer

Its action is similar to that of amiloride.

Answer

It is a potassium-sparing diuretic.

Question 10

What is the mechanism of action of bumetanide?

Accepted Answer

Loop diuretic

Answer

Angiotensin converting enzyme inhibitor

Answer

Carbonic anhydrase inhibitor

Answer

Potassium sparing diuretic

Diuretics — MCQs

Diuretics — MCQs

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