Diuretics

Diuretics Indian Medical PG Question 1: Mannitol is used in the management of:-

• A. Acute renal failure
• B. Pulmonary edema
• C. Congestive cardiac failure
• D. Acute angle-closure glaucoma (Correct Answer)

Diuretics Explanation: ***Acute angle-closure glaucoma*** - **Mannitol** is an osmotic diuretic [1] used to rapidly reduce **intraocular pressure** in conditions like acute angle-closure glaucoma [2]. - It works by creating an **osmotic gradient** that draws fluid from the vitreous humor into the bloodstream [2]. - This is a well-established **emergency indication** for mannitol [2]. *Acute renal failure* - While mannitol may be used in **prevention** of acute kidney injury (e.g., in rhabdomyolysis, cardiovascular surgery) [2], its use in established acute renal failure is generally **contraindicated** if the patient is **anuric**, as it can exacerbate fluid overload [2]. - It is **not a primary management** for acute renal failure among the given options. *Pulmonary edema* - **Mannitol** is generally **contraindicated** in pulmonary edema because its initial effect is to increase **intravascular volume** [2], which can worsen fluid accumulation in the lungs. - Loop diuretics like **furosemide** are preferred for their rapid onset and profound diuretic effect in pulmonary edema. *Congestive cardiac failure* - **Mannitol** is typically **contraindicated** in congestive cardiac failure as it can cause a **transient increase in plasma volume**, potentially worsening cardiac workload and leading to decompensation [2]. - Diuretics commonly used in heart failure, such as **loop diuretics** (e.g., furosemide) or **thiazide diuretics**, are preferred to reduce fluid overload.

Diuretics Indian Medical PG Question 2: Hydrochlorothiazide works by inhibiting

• A. Na+ Cl pump in late DCT
• B. Na+ K+ 2Cl pump in descending limb of loop of Henle
• C. Na+ K+ 2Cl pump in ascending limb of loop of Henle
• D. Na+ Cl pump in early DCT (Correct Answer)

Diuretics Explanation: ***Na+ Cl pump in early DCT*** - **Hydrochlorothiazide** is a **thiazide diuretic** that acts primarily on the **early distal convoluted tubule (DCT)**. - It inhibits the **sodium-chloride cotransporter (NCC)**, leading to increased excretion of sodium, chloride, and water. *Na+ Cl pump in late DCT* - The **late DCT** and collecting duct are primarily involved in fine-tuning sodium reabsorption, influenced by **aldosterone**, not the primary site of action for thiazides. - The **epithelial sodium channel (ENaC)** and Na+/K+-ATPase are more prominent here. *Na+ K+ 2Cl pump in descending limb of loop of Henle* - The **descending limb of the loop of Henle** is primarily permeable to water, with no active ion pumps like **Na+ K+ 2Cl pump**. - Its main function is to concentrate the urine by allowing water to move out. *Na+ K+ 2Cl pump in ascending limb of loop of Henle* - **Furosemide** and other **loop diuretics** act on the **Na+ K+ 2Cl cotransporter (NKCC2)** in the **thick ascending limb of the loop of Henle**, not hydrochlorothiazide. - Inhibition here prevents significant reabsorption of sodium, potassium, and chloride, leading to potent diuresis.

Diuretics Indian Medical PG Question 3: Which one of the following drugs causes increased concentration of Na+ & Cl- in urine with normal bicarbonate?

• A. Furosemide
• B. Ethacrynic acid (Correct Answer)
• C. Bumetanide
• D. Acetazolamide

Diuretics Explanation: ***Ethacrynic acid*** - Ethacrynic acid is a **loop diuretic** that inhibits the Na+-K+-2Cl- cotransporter in the **thick ascending limb of the loop of Henle**. - It causes increased urinary excretion of **Na+ and Cl-** while maintaining **normal bicarbonate levels** (does not affect carbonic anhydrase). - **Key distinguishing feature**: Ethacrynic acid is a **phenoxyacetic acid derivative** (NOT a sulfonamide), making it useful in patients with **sulfonamide allergies**. - Note: All loop diuretics share the property of increasing Na+ and Cl- excretion with normal bicarbonate. *Furosemide* - Furosemide is a **sulfonamide-derived loop diuretic** with the same mechanism as ethacrynic acid (inhibits Na+-K+-2Cl- cotransporter). - It also increases Na+ and Cl- excretion with normal bicarbonate levels. - While pharmacologically equivalent to ethacrynic acid for this effect, it is structurally different (sulfonamide derivative). *Bumetanide* - Bumetanide is another **sulfonamide-derived loop diuretic** with identical mechanism to furosemide and ethacrynic acid. - It produces the same electrolyte effects: increased Na+ and Cl- excretion with normal bicarbonate. - Structurally, it is a sulfonamide derivative like furosemide. *Acetazolamide* - Acetazolamide is a **carbonic anhydrase inhibitor** acting in the **proximal tubule**. - It increases excretion of **bicarbonate** (causing metabolic acidosis), along with Na+ and K+. - This would result in **elevated bicarbonate in urine**, NOT normal bicarbonate, making it incorrect.

Diuretics Indian Medical PG Question 4: Which of the following potassium-sparing diuretics was the first to be shown to reduce cardiac mortality in chronic heart failure patients?

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

Diuretics Explanation: ***Spironolactone*** - **Spironolactone** was the first potassium-sparing diuretic shown to reduce **cardiac mortality** in patients with **chronic heart failure** in the **RALES trial** (Randomized Aldactone Evaluation Study). - Its beneficial effects in heart failure are primarily attributed to its **aldosterone receptor antagonist** properties, which counteract the harmful effects of aldosterone on the myocardium and vasculature, rather than just its diuretic effect. *Amiloride* - **Amiloride** is a potassium-sparing diuretic that works by directly inhibiting **epithelial sodium channels (ENaC)** in the collecting duct. - While it helps in potassium conservation, it has not been shown to significantly reduce cardiac mortality in chronic heart failure patients in clinical trials. *Triamterene* - **Triamterene** is another potassium-sparing diuretic that also directly inhibits **ENaC** in the collecting duct, similar to amiloride. - Like amiloride, it is used to prevent hypokalemia but lacks evidence for significant **cardiac mortality reduction** in chronic heart failure. *Eplerenone* - **Eplerenone** is a selective **aldosterone receptor antagonist**, similar to spironolactone, with fewer hormonal side effects. - While it has been shown to reduce **cardiac mortality** in chronic heart failure (e.g., in the EMPHASIS-HF trial), it was introduced later than spironolactone and was not the *first* to demonstrate this benefit.

Diuretics Indian Medical PG Question 5: A 42-year old man with history of alcohol dependency presents with progressive abdominal distension. Abdominal examination reveals a shifting dullness. Which one of the following is the most appropriate drug to relieve this abdominal distension?

• A. Lactulose
• B. Spironolactone (Correct Answer)
• C. Propranolol
• D. Octreotide

Diuretics Explanation: **Spironolactone** - **Spironolactone** is an **aldosterone antagonist**, which is the **first-line diuretic** used in the management of **ascites** due to **cirrhosis**, often developing secondary to alcohol dependency. - It works by blocking aldosterone receptors in the **renal collecting duct**, leading to increased sodium and water excretion while conserving potassium, effectively reducing fluid accumulation. *Lactulose* - **Lactulose** is a non-absorbable disaccharide primarily used to treat and prevent **hepatic encephalopathy** by reducing ammonia levels. - It does not directly relieve abdominal distension caused by ascites, and its use is unrelated to fluid overload. *Propranolol* - **Propranolol** is a **non-selective beta-blocker** used to reduce **portal pressure** and prevent **variceal bleeding** in patients with cirrhosis. - While it addresses a complication of chronic liver disease, it does not directly manage or relieve ascites. *Octreotide* - **Octreotide** is a **somatostatin analog** used to treat complications like **acute variceal bleeding** or **hepatic encephalopathy** by reducing splanchnic blood inflow. - It is not indicated for the management of ascites or relief of abdominal distension caused by fluid accumulation.

Diuretics Flashcard 1 of 5

Question: Renal (Diuretics) _____ diuretics may cause hypo-natremia as an adverse effect

Answer: Thiazide

Diuretics Flashcard 2 of 5

Question: Mannitol is contraindicated in patients with _____ and/or heart failure

Answer: anuria

Diuretics Flashcard 3 of 5

Question: One adverse effect of K+ sparing diuretics is _____, which increases risk for arrhythmia

Answer: hyperkalemia

Diuretics Flashcard 4 of 5

Question: _____ diuretics indirectly inhibit Ca2+ and Mg2+ reabsorption in the thick ascending limb (loop of Henle)

Answer: Loop

Diuretics Flashcard 5 of 5

Question: Drug of choice for Mountain sickness:

Answer: Acetazolamide