Pharmacology
Diuretics — loop, thiazide, K-sparing
Pharmacology

Diuretics — loop, thiazide, K-sparing

Where they act in the nephron, what they do to electrolytes, what they cause.

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Loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid)

  • Site: thick ascending limb (NKCC2 blocker)
  • Effects: ↑↑ Na, K, Cl, Ca, Mg, H+ excretion; massive diuresis
  • Indications: HF, pulmonary edema, severe HTN, hypercalcemia, refractory edema
  • Side effects: hypokalemia, hypomagnesemia, hypocalcemia, metabolic alkalosis, hyperuricemia (→ gout), ototoxicity (esp. with aminoglycosides)
  • Ethacrynic acid: only loop usable in true sulfa allergy

Thiazides (HCTZ, chlorthalidone, indapamide)

  • Site: distal convoluted tubule (NCC blocker)
  • Effects: moderate diuresis; HOLDS calcium (treats hypercalciuria, stones)
  • Indications: essential HTN (first-line), CHF (less effective than loop), calcium-stone prophylaxis, nephrogenic DI
  • Side effects: 'hyperGLUC' = HYPERglycemia, HYPERlipidemia, HYPERuricemia (gout), HYPERcalcemia; HYPOnatremia, HYPOkalemia, HYPOmagnesemia
  • Chlorthalidone preferred over HCTZ (longer half-life, better BP control)

K-sparing (spironolactone, eplerenone, amiloride, triamterene)

  • Spironolactone, eplerenone: aldosterone receptor antagonists
  • Amiloride, triamterene: ENaC blockers (collecting duct)
  • Indications: HFrEF mortality benefit (spironolactone, eplerenone), hyperaldosteronism, cirrhosis with ascites, refractory HTN, acne in women, PCOS
  • Side effects: HYPERkalemia, gynecomastia (spironolactone, NOT eplerenone), metabolic acidosis
  • Monitor K every 1–2 weeks initially, then every 3 months

Other

  • Mannitol (osmotic): ↑ ICP, glaucoma; CAN cause pulmonary edema
  • Acetazolamide (CA inhibitor): altitude sickness prophylaxis, glaucoma, idiopathic intracranial HTN; causes metabolic acidosis

Diuretic electrolyte effects at a glance

DrugEffect
Furosemide↓ K, Mg, Ca; metabolic alkalosis
HCTZ↓ K, Na; ↑ Ca, glucose, uric acid
Spironolactone↑ K; gynecomastia (men)
Acetazolamide↓ K, HCO₃; metabolic acidosis
MannitolVolume shift; risk of pulm edema

High-yield pearls

  • Calcium stones → THIAZIDE (lowers urine Ca via DCT reabsorption)
  • Cirrhosis ascites → SPIRONOLACTONE first-line (high aldosterone in cirrhosis)
  • HCTZ + lithium → ↑ lithium levels (renal reabsorption)
  • Loop + aminoglycoside → ototoxicity
  • Spironolactone gynecomastia → switch to ELPERENONE (selective MR antagonist)
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