Diuretics · Medical Notes

💊 Diuretic pharmacology · core concepts

Diuretics increase urine output by inhibiting Na⁺ reabsorption at specific nephron segments
Major classes: osmotic, carbonic anhydrase inhibitors, loop, thiazide, K⁺-sparing
Site of action determines electrolyte effects and clinical indications
Most diuretics (except K⁺-sparing) cause hypokalemia and metabolic alkalosis

          High-yield: loop diuretics promote Ca²⁺ excretion; thiazides reduce Ca²⁺ excretion

        

Drug: Mannitol (IV)
Mechanism: increases osmotic pressure in tubular lumen → inhibits water reabsorption along entire nephron
Uses:
- Reduce intraocular pressure (glaucoma)
- Decrease intracerebral pressure (cerebral edema)
- Oliguric states (e.g., rhabdomyolysis-induced acute kidney injury)
Side effects: acute hypovolemia, hypernatremia (if water loss exceeds Na⁺)
⚠️ Contraindicated in CHF and pulmonary edema — expands intravascular volume transiently

Drugs: acetazolamide (oral/IV), dorzolamide (topical)
Mechanism: inhibit carbonic anhydrase in PCT → ↓ H⁺ formation → ↓ Na⁺/H⁺ exchange → ↑ luminal Na⁺ & HCO₃⁻ → diuresis
Uses:
- Glaucoma (↓ aqueous humor production)
- Acute mountain sickness (prophylaxis & treatment)
- Metabolic alkalosis (corrects alkalemia)
Side effects:
- Bicarbonaturia → metabolic acidosis
- Hypokalemia (due to distal Na⁺ delivery)
- Hyperchloremia, paresthesias, renal stones (calcium phosphate)
- Sulfonamide hypersensitivity (cross-reactivity)

Drugs: furosemide, torsemide, ethacrynic acid
Site: thick ascending limb (TAL) — Na⁺/K⁺/2Cl⁻ cotransporter
Effects: ↓ intracellular K⁺ → ↓ positive luminal potential → ↓ Ca²⁺ & Mg²⁺ reabsorption
Uses:
- Acute pulmonary edema / CHF
- Hypertension (especially with renal impairment)
- Refractory edema (nephrotic syndrome, cirrhosis)
- Hypercalcemic states (limited use)
Adverse effects:
- Hypokalemia, metabolic alkalosis
- Hypocalcemia, hypomagnesemia
- Hyperuricemia (OAT-mediated secretion)
- Ototoxicity (ethacrynic acid > furosemide; risk with aminoglycosides)
- Sulfonamide hypersensitivity (except ethacrynic acid)
Drug interactions: aminoglycosides (↑ ototoxicity), lithium (↓ clearance), digoxin (↑ toxicity due to electrolyte shifts)

TAL inhibition → ↓ K⁺ back-diffusion → ↓ lumen positive potential → ↓ Ca²⁺/Mg²⁺ reabsorption

Drugs: hydrochlorothiazide, chlorthalidone, indapamide
Site: distal convoluted tubule (DCT) — Na⁺/Cl⁻ cotransporter
Mechanism: inhibit Na⁺/Cl⁻ reabsorption → ↑ luminal Na⁺ & Cl⁻ → diuresis
Uses:
- Hypertension (first-line)
- CHF (mild-moderate edema)
- Nephrolithiasis (calcium stones — ↓ urine Ca²⁺)
- Nephrogenic diabetes insipidus (paradoxical antidiuretic effect)
Side effects:
- Hypokalemia, metabolic alkalosis
- Hypercalcemia (↑ Ca²⁺ reabsorption in DCT)
- Hyperuricemia, hyperglycemia, hyperlipidemia (except indapamide)
- Sulfonamide hypersensitivity
Drug caution: digoxin toxicity (↑ risk due to K⁺ depletion)

          Thiazides also hyperpolarize smooth muscle (vasodilation) and pancreatic β-cells (↓ insulin release)

        

Drugs: amiloride, triamterene, spironolactone (aldosterone antagonist)
Site: collecting duct (principal cells)
Mechanism: block Na⁺ channels (amiloride/triamterene) or aldosterone receptors (spironolactone) → ↓ Na⁺ reabsorption, ↓ K⁺ secretion
Uses: hypertension, CHF, cirrhosis (adjunct to prevent hypokalemia)
Side effects: hyperkalemia (especially with ACEIs/ARBs), gynecomastia (spironolactone)
⚠️ Avoid K⁺ supplements and K⁺-rich diets during therapy.

          Loop and thiazide diuretics increase distal Na⁺ delivery → enhanced K⁺/H⁺ loss → hypokalemia & alkalosis

        

Sulfonamide cross-allergenicity: CA inhibitors, loop (except ethacrynic acid), thiazides, sulfa antibiotics, celecoxib
Loop vs thiazide calcium effect: loops ↑ Ca²⁺ excretion; thiazides ↓ Ca²⁺ excretion
Osmotic diuretics: contraindicated in CHF/pulmonary edema due to transient volume expansion
Hyperkalemia risk: K⁺-sparing + ACEI/ARB combination
Ototoxicity: ethacrynic acid > furosemide; enhanced by aminoglycosides