Spironolactone
Aldactone
Aldosterone receptor antagonist (potassium-sparing)
Competitive antagonist at the mineralocorticoid receptor in the distal nephron → inhibits aldosterone-mediated Na reabsorption + K secretion. Net effect: mild Na/water loss + K retention + Mg retention. Also a weak androgen-receptor antagonist.
Indications
- •CHF — mortality benefit in NYHA III/IV (RALES NEJM 1999) and post-MI LV dysfunction (EPHESUS NEJM 2003)
- •Resistant hypertension
- •Cirrhotic ascites (first-line — block aldosterone surge of cirrhosis)
- •Primary hyperaldosteronism (Conn's)
- •Hirsutism / acne in PCOS (anti-androgen effect)
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Heart failure | 12.5–25 mg PO daily; titrate to 50 mg max if tolerated | — |
| Resistant HTN | 12.5–50 mg PO daily | — |
| Cirrhotic ascites | 100 mg PO daily, titrate up to 400 mg | — |
Pharmacokinetics
Onset 24–48 h (slow — receptor occupancy takes time). Half-life 1.4 h parent / 14 h active metabolite (canrenone). Hepatic metabolism.
Hemodynamic effects
Modest BP reduction at heart-failure doses; more substantial in resistant HTN.
Respiratory effects
None directly.
Side effects
- !Hyperkalemia (life-threatening in CKD or with ACE/ARB combination — RALES post-publication mortality bumped from inappropriate dosing)
- !Gynecomastia + breast tenderness in men (anti-androgen)
- !Menstrual irregularities in women
- !Hyponatremia
- !Acute kidney injury
Contraindications
- ×Hyperkalemia (K > 5.0)
- ×Severe renal failure (CrCl <30)
- ×Addison's disease
- ×Concurrent K-sparing diuretics or K supplements without monitoring
Clinical pearls
- ★RALES (NEJM 1999): in NYHA III/IV CHF on standard therapy, spironolactone 25 mg/day reduced mortality 30% — paradigm-changing trial. EPHESUS (eplerenone, post-MI) confirmed in different population.
- ★POST-RALES K SAFETY: real-world hyperkalemia hospitalizations spiked after RALES because clinicians added it to ACEi without K monitoring. Now standard: check K + Cr before, q1 wk × 1 mo, then q3 mo.
- ★HYPERK + ACEi/ARB COMBO: spironolactone + lisinopril doubles hyperK risk. Avoid in CKD stage 3+ unless cardiology insists; monitor closely.
- ★EPLERENONE: more selective mineralocorticoid antagonist with no anti-androgen effect — preferred over spironolactone in men intolerant of gynecomastia.
📊 Related teaching panels
Standalone diagrams matched to this topic.
Other drugs in Diuretics
- Furosemide
Inhibits the Na-K-2Cl cotransporter in the thick ascending loop of Henle. Massive natriuresis + kaliuresis + magnesiuresis. Also a venodilator — drops preload within minutes, before diuresis kicks in.
- Mannitol
Freely filtered, not reabsorbed. Pulls water from tissues into vascular space (transient ↑intravascular volume) then drives osmotic diuresis. Reduces ICP by drawing water across an intact blood-brain barrier.
- Acetazolamide
Reversibly inhibits carbonic anhydrase in proximal renal tubule, choroid plexus, ciliary body, RBC. Renal effect: ↓Na/H exchange → bicarbonate diuresis + mild Na/water loss + metabolic acidosis. CNS effect: ↓CSF production. Eye effect: ↓aqueous humor.
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