Diuretics
On board day, diuretic questions hinge on matching the right diuretic to the right clinical problem and predicting the electrolyte fallout. Thiazides (hydrochlorothiazide, chlorthalidone) are first-line for hypertension and cause hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, and hypercalcemia. Loop diuretics (furosemide, torsemide, bumetanide) are the volume-overload workhorse in heart failure and CKD and waste calcium and potassium. Potassium-sparing agents split into two: aldosterone antagonists (spironolactone, eplerenone), which add HFrEF mortality benefit, and ENaC blockers (amiloride, triamterene). The exam tests recognizing thiazide-induced hyponatremia in older women, gynecomastia from spironolactone, and the loop-and-thiazide combination for diuretic resistance.
📖 Overview
Thiazides (HCTZ, chlorthalidone) act on the distal convoluted tubule and are first-line for uncomplicated HTN. Loop diuretics (furosemide) act on the thick ascending loop of Henle — most potent diuretic class, used in volume overload (CHF, pulmonary edema, cirrhotic ascites). Potassium-sparing diuretics (spironolactone) block aldosterone, used in CHF, resistant HTN, and hyperaldosteronism.
⚙️ Mechanism of Action
Thiazide: blocks Na-Cl symporter in DCT. Loop: blocks Na-K-2Cl symporter in thick ascending limb. Spironolactone: aldosterone antagonist in collecting duct.
💎 Board Pearls
- ⚡ Thiazides → ↑Ca²⁺, ↑uric acid (gout!), ↑glucose, ↓K, ↓Na, ↓Mg.
- ⚡ Loops → ↓Ca²⁺, ↑uric acid, ↓K, ↓Na, ↓Mg, ototoxicity at high IV doses.
- 💊 Chlorthalidone > HCTZ for BP control (longer half-life, more outcome data).
- 🍌 Spironolactone → HYPERkalemia + gynecomastia in men.
- 🚫 Sulfa allergy: thiazides + loops contain a sulfonamide group (caution but usually tolerated).
- 💡 CHF regimen: ACEi + β-blocker + spironolactone (mortality trio) + loop PRN for congestion.
💊 Drugs in This Class
- Hydrochlorothiazide — HCTZ, MicrozideHTN (first-line), edema, nephrogenic diabetes insipidus.
- Chlorthalidone — Hygroton, ThalitoneHTN (preferred over HCTZ per AHA), CHF edema.
- Furosemide — LasixCHF/pulmonary edema, ascites, severe HTN, AKI/CKD fluid overload.
- Spironolactone — AldactoneHFrEF (mortality benefit), resistant HTN, primary hyperaldosteronism, cirrhotic ascites, acne/hirsutism (off-label).
Practice Questions
Which of the following sets of laboratory abnormalities BEST represents the classic metabolic profile of long-term thiazide diuretic therapy (the "6 H's")?
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