Thiazide and Thiazide-Like Diuretics — MCQs
All of the following adverse effects can be caused by loop diuretics except :
Mechanism of action of thiazides is by -
How do thiazides cause hypercalcemia?
Thiazides and loop diuretics both have opposite action on which of the following ions ?
Which electrolyte shows the most significant increase in urinary excretion within 24 hours of initiating thiazide diuretic therapy for hypertension?
Which diuretic is known to cause the maximum potassium loss?
All of the following diuretics increase K+ excretion EXCEPT:
Which diuretic is most likely to cause hyponatremia by impairing free water excretion?
In which segment of the nephron does ethacrynic acid exert its diuretic action?
A patient on lithium therapy developed hypertension and was started on a thiazide diuretic. After a few days, he developed coarse tremors and other symptoms suggestive of lithium toxicity. What is the probable mechanism of interaction between thiazide diuretics and lithium?
Thiazide and Thiazide-Like Diuretics Indian Medical PG Practice Questions and MCQs
Question 1: All of the following adverse effects can be caused by loop diuretics except :
- A. Hypomagnesemia
- B. Hyperglycemia
- C. Hypercalcemia (Correct Answer)
- D. Hyperuricemia
Explanation: ***Hypercalcemia*** - Loop diuretics inhibit the reabsorption of calcium in the thick ascending limb of the loop of Henle, leading to **increased calcium excretion** and thus **hypocalcemia**, not hypercalcemia [2]. - This property makes them useful in treating conditions like hypercalcemia, but it means they do not cause hypercalcemia themselves. *Hypomagnesemia* - Loop diuretics inhibit magnesium reabsorption in the thick ascending limb, leading to **increased urinary magnesium excretion** and potential **hypomagnesemia** [1], [2]. - This electrolyte imbalance can contribute to cardiac arrhythmias and muscle weakness [2]. *Hyperglycemia* - Loop diuretics, particularly in high doses, can decrease **insulin secretion** and increase **insulin resistance**, leading to **hyperglycemia**. - This effect is generally mild but can be significant in patients with **diabetes mellitus**. *Hyperuricemia* - Loop diuretics compete with uric acid for secretion into the renal tubules, leading to **reduced uric acid excretion** and elevated serum uric acid levels, also known as **hyperuricemia** [1]. - This can precipitate or exacerbate **gout attacks** in susceptible individuals [1].
Question 2: Mechanism of action of thiazides is by -
- A. Inhibiting Na+K+2Cl- in ascending limb of loop of henle
- B. Inhibiting Na+/Cl- symporter in DCT (Correct Answer)
- C. Inhibiting Na+/Cl- symporter in PCT
- D. Inhibiting Na+K+2Cl- in descending limb of loop of henle
Explanation: **Inhibiting Na+/Cl- symporter in DCT** - Thiazide diuretics primarily act on the **distal convoluted tubule (DCT)** of the nephron [2]. - They inhibit the **Na+/Cl- symporter** (NCC channel) on the apical membrane, preventing reabsorption of sodium and chloride ions [1], [2]. *Inhibiting Na+K+2CI- in descending limb of loop of henle* - The descending limb of the loop of Henle is permeable to water but largely impermeable to solutes; there is no significant Na+K+2Cl- symporter activity here. - This mechanism describes the action of loop diuretics, but they act on the **ascending** limb, not the descending limb. *Inhibiting Na+K+2Cl- in ascending limb of loop of henle* - This mechanism describes the action of **loop diuretics** (e.g., furosemide, bumetanide) [3]. - Loop diuretics inhibit the **Na+K+2Cl- cotransporter (NKCC2)** in the thick ascending limb of the loop of Henle, leading to significant diuresis [3]. *Inhibiting Na+/Cl- symporter in PCT* - The **proximal convoluted tubule (PCT)** is primarily responsible for reabsorbing most of the filtered sodium, chloride, bicarbonate, and other solutes. - While sodium is reabsorbed in the PCT, it's mainly through Na+/H+ exchangers and other mechanisms, not a specific Na+/Cl- symporter that is targeted by thiazides [2].
Question 3: How do thiazides cause hypercalcemia?
- A. Decreased calcium excretion (Correct Answer)
- B. Increased parathyroid hormone secretion
- C. Decreased calcitonin secretion
- D. Increased calcium absorption
Explanation: ***Decreased calcium excretion*** - Thiazides inhibit the **Na-Cl co-transporter** in the **distal convoluted tubule**, leading to increased reabsorption of calcium [1], [2]. - This increased reabsorption of calcium is mediated by a low intracellular sodium concentration, which enhances the activity of the **Na+/Ca2+ exchanger** on the basolateral membrane [1]. *Increased parathyroid hormone secretion* - Thiazides **do not directly stimulate** parathyroid hormone (PTH) secretion; instead, they *decrease* calcium excretion, which would typically *lower* PTH levels through negative feedback. - Elevated PTH would lead to increased bone resorption and kidney calcium reabsorption, but this is not the **primary mechanism** for thiazide-induced hypercalcemia [2]. *Decreased calcitonin secretion* - **Calcitonin** is a hormone that *lowers* blood calcium levels, and its decrease would theoretically contribute to hypercalcemia. - However, thiazides have **no direct effect** on calcitonin secretion, making this an unlikely primary mechanism. *Increased calcium absorption* - While increased calcium absorption from the gut can contribute to hypercalcemia, thiazides do **not directly increase intestinal calcium absorption**. - Their primary action for influencing calcium levels is within the **kidney**, specifically on reabsorption, not absorption from the GI tract [1], [2].
Question 4: Thiazides and loop diuretics both have opposite action on which of the following ions ?
- A. Potassium
- B. Sodium
- C. Chloride
- D. Calcium (Correct Answer)
Explanation: ***Calcium*** - Thiazide diuretics **increase calcium reabsorption** in the distal convoluted tubule, leading to decreased urinary calcium excretion. - Loop diuretics **decrease calcium reabsorption** in the thick ascending limb of the loop of Henle, resulting in increased urinary calcium excretion. *Potassium* - Both thiazide and loop diuretics can cause **hypokalemia** by increasing potassium excretion in the urine. - This is due to increased sodium delivery to the collecting duct, which stimulates potassium secretion. *Sodium* - Both thiazide and loop diuretics inhibit sodium reabsorption at different sites in the nephron, leading to **increased urinary sodium excretion** (natriuresis). - This is their primary mechanism of action for diuresis. *Chloride* - Both thiazide and loop diuretics inhibit **chloride reabsorption** as they block specific sodium-chloride cotransporters. - Thiazides inhibit the Na-Cl cotransporter in the DCT, while loop diuretics inhibit the Na-K-2Cl cotransporter in the thick ascending limb.
Question 5: Which electrolyte shows the most significant increase in urinary excretion within 24 hours of initiating thiazide diuretic therapy for hypertension?
- A. Sodium (Correct Answer)
- B. Potassium
- C. Magnesium
- D. Calcium
Explanation: ***Sodium*** - Thiazide diuretics primarily act on the **distal convoluted tubule** by inhibiting the **Na+/Cl- cotransporter**, leading to increased excretion of **sodium** and water [1]. - The initial and most significant pharmacological effect of thiazides is to promote **natriuresis**, removing excess sodium from the body [2]. - Within **24 hours**, sodium excretion shows the most pronounced increase, which is the primary mechanism for blood pressure reduction [2]. *Potassium* - While thiazides do cause **potassium excretion**, this effect is less significant than sodium excretion initially and is partly due to increased flow to the collecting duct and elevated aldosterone levels [2]. - Hypokalemia is a known side effect of long-term thiazide use, but the **immediate increase in urinary sodium** is more pronounced. *Magnesium* - Thiazide diuretics are known to cause **increased urinary excretion of magnesium**, which can lead to hypomagnesemia with chronic use [3]. - However, the initial increase in magnesium excretion is generally **less pronounced** compared to sodium excretion within the first 24 hours of therapy. *Calcium* - Uniquely among diuretics, thiazides **decrease** urinary calcium excretion, promoting calcium retention and reabsorption in the distal tubule [1], [3]. - This is why thiazides are sometimes used therapeutically in **hypercalciuric nephrolithiasis** and can cause hypercalcemia as a side effect. - Calcium excretion is **reduced**, not increased, making this the opposite of the correct answer.
Question 6: Which diuretic is known to cause the maximum potassium loss?
- A. Spironolactone
- B. Furosemide (Correct Answer)
- C. Thiazide diuretics
- D. Acetazolamide
Explanation: ***Furosemide*** - Furosemide is a **loop diuretic** that inhibits the Na-K-2Cl cotransporter in the **thick ascending limb of the loop of Henle**, leading to significant excretion of sodium, chloride, potassium, and water. - Its potent diuresis and impact on potassium reabsorption result in a **high risk of hypokalemia**. *Thiazide* - Thiazide diuretics inhibit the **Na-Cl cotransporter** in the **distal convoluted tubule**, causing moderate sodium and water excretion, and some potassium loss. - While they can cause hypokalemia, their effect on potassium excretion is generally **less pronounced than loop diuretics**. *Acetazolamide* - Acetazolamide is a **carbonic anhydrase inhibitor** that acts primarily in the **proximal tubule**, inhibiting bicarbonate reabsorption and leading to increased excretion of bicarbonate, sodium, potassium, and water. - The potassium loss is due to increased delivery of sodium to the collecting duct, leading to enhanced potassium secretion, but it is typically **less severe than with loop diuretics**. *Spironolactone* - Spironolactone is a **potassium-sparing diuretic** that acts as an **aldosterone antagonist** in the collecting duct, inhibiting sodium reabsorption and potassium secretion. - Instead of causing potassium loss, spironolactone actually **conserves potassium** and can lead to hyperkalemia.
Question 7: All of the following diuretics increase K+ excretion EXCEPT:
- A. Acetazolamide
- B. Triamterene (Correct Answer)
- C. Thiazide
- D. Furosemide
Explanation: ***Triamterene*** - **Triamterene** is a **potassium-sparing diuretic** that blocks epithelial sodium channels (ENaC) in the collecting duct, thereby reducing sodium reabsorption and potassium secretion. - Unlike most other diuretics, it causes **decreased K+ excretion** and can lead to hyperkalemia. *Acetazolamide* - **Acetazolamide** is a **carbonic anhydrase inhibitor** that acts in the proximal tubule, inhibiting bicarbonate reabsorption. - This leads to increased delivery of sodium and bicarbonate to the collecting duct, which enhances **potassium secretion** and increases K+ excretion. *Thiazide* - **Thiazide diuretics** (e.g., hydrochlorothiazide) act by inhibiting the Na+/Cl- cotransporter in the **distal convoluted tubule**. - This increases the delivery of sodium to the collecting duct, which stimulates the exchange of sodium for **potassium**, leading to increased K+ excretion and hypokalemia. *Furosemide* - **Furosemide** is a **loop diuretic** that inhibits the Na+/K+/2Cl- cotransporter in the **thick ascending limb of the loop of Henle**. - This prevents the reabsorption of these ions, leading to increased delivery of sodium to the collecting duct, which promotes **potassium secretion** and increased K+ excretion.
Question 8: Which diuretic is most likely to cause hyponatremia by impairing free water excretion?
- A. Loop diuretics
- B. Acetazolamide
- C. Amiloride
- D. Thiazide diuretics (Correct Answer)
Explanation: ***Thiazide diuretics*** - **Thiazide diuretics** inhibit the **Na-Cl cotransporter in the distal convoluted tubule (DCT)**, impairing the kidney's ability to dilute urine and excrete free water - This impaired urinary dilution leads to **water retention relative to sodium**, resulting in **dilutional hyponatremia** - **Most common in elderly patients**, those on low-salt diets, or with pre-existing volume depletion - **Mechanism**: By blocking sodium reabsorption in the DCT (a key site for urinary dilution), thiazides prevent the generation of free water, leading to hyponatremia when water intake continues *Loop diuretics* - **Loop diuretics** inhibit the **Na-K-2Cl cotransporter in the thick ascending limb of Henle**, causing significant diuresis - They impair the medullary concentration gradient, **enhancing free water excretion** - **Less likely to cause hyponatremia** compared to thiazides because they promote rather than impair free water clearance - When hyponatremia occurs with loop diuretics, it's usually due to concurrent SIADH or excessive free water intake *Acetazolamide* - **Acetazolamide** is a **carbonic anhydrase inhibitor** acting primarily on the **proximal tubule** - Causes **bicarbonate and sodium excretion**, leading to mild diuresis - Main side effect is **metabolic acidosis** (type 2 RTA) - **Does not significantly impair free water excretion**, making hyponatremia uncommon *Amiloride* - **Amiloride** is a **potassium-sparing diuretic** that blocks **epithelial sodium channels (ENaC) in the collecting duct** - Weak diuretic effect, primarily used to prevent potassium loss - **Does not impair urinary dilution mechanisms**, so hyponatremia is rare - Main concern is **hyperkalemia**, especially with ACE inhibitors or in renal insufficiency
Question 9: In which segment of the nephron does ethacrynic acid exert its diuretic action?
- A. Proximal convoluted tubule
- B. Collecting duct
- C. Distal convoluted tubule
- D. Thick ascending limb of loop of Henle (Correct Answer)
Explanation: ***Thick ascending limb of loop of Henle*** - Ethacrynic acid is a **loop diuretic** that acts by inhibiting the **Na+-K+-2Cl- cotransporter** (NKCC2) in the luminal membrane of the thick ascending limb. - This inhibition prevents the reabsorption of ions, leading to increased excretion of water, sodium, chloride, and potassium. *Proximal convoluted tubule* - The proximal convoluted tubule is the primary site of reabsorption of most filtered substances, but loop diuretics like ethacrynic acid do not primarily act here. - Carbonic anhydrase inhibitors and SGLT2 inhibitors are examples of diuretics that exert their effects in this segment. *Collecting duct* - The collecting duct is the site where aldosterone antagonists (e.g., spironolactone) and epithelial sodium channel (ENaC) inhibitors (e.g., amiloride, triamterene) exert their diuretic effects. - Its primary role involves fine-tuning water reabsorption under the influence of ADH and regulating potassium excretion. *Distal convoluted tubule* - Thiazide diuretics primarily act in the distal convoluted tubule by inhibiting the **Na+-Cl- cotransporter** (NCC). - This segment is responsible for further diluting the urine and reabsorbing a small percentage of filtered sodium and chloride.
Question 10: A patient on lithium therapy developed hypertension and was started on a thiazide diuretic. After a few days, he developed coarse tremors and other symptoms suggestive of lithium toxicity. What is the probable mechanism of interaction between thiazide diuretics and lithium?
- A. Thiazide increases the tubular reabsorption of lithium (Correct Answer)
- B. Thiazide inhibits the metabolism of lithium
- C. Thiazides act as an add-on drug to lithium
- D. None of the above
Explanation: ***Thiazide increases the tubular reabsorption of lithium*** - Thiazide diuretics cause a decrease in sodium reabsorption in the distal convoluted tubule, leading to increased sodium excretion in urine. - The kidneys, in an attempt to conserve sodium, increase reabsorption in the proximal tubule. Because **lithium** is reabsorbed similarly to sodium in the proximal tubule, this increased reabsorption also affects lithium, leading to a rise in its plasma concentration and toxicity. *Thiazide inhibits the metabolism of lithium* - Lithium is primarily excreted by the kidneys and is not significantly metabolized in the body. - Thiazide diuretics do not affect enzyme systems responsible for drug metabolism. *Thiazides act as an add on the drug to lithium* - This statement is vague and does not explain a mechanism of interaction leading to toxicity. - While both drugs might be prescribed concurrently for different conditions, "add on" does not describe a pharmacological interaction causing altered drug levels. *None of the above* - This option is incorrect because a clear and well-understood mechanism for the interaction between thiazide diuretics and lithium exists.
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