Generic Name

Spironolactone

Mechanism

• Spironolactone is a competitive antagonist of mineralocorticoid receptors in the late distal tubule and collecting duct.
• It blocks the action of aldosterone, preventing Na⁺ reabsorption and K⁺ excretion, resulting in natriuresis and potassium‑retention.
• Its anti‑androgen activity arises from:
• Receptor blockade of androgen receptors in skin and ovarian tissues.
• Inhibition of steroid sulfatase and 5‑α‑reductase, decreasing androgen synthesis.
• These properties underlie its utility in both fluid‑volume disorders and hyperandrogenic conditions.

Pharmacokinetics

• Absorption: Oral bioavailability ~30 %–40 % (first‑pass metabolism).
• Distribution: High plasma protein binding (~92 %), crosses the placenta; limited blood‑brain barrier penetration.
• Metabolism: Hepatic conversion to active metabolites—canrenone and spironolactone‑hemiketal—which retain mineralocorticoid antagonism.
• Half‑life: 1–4 h for parent drug; 4–6 h for canrenone; cumulative effects may persist >24 h due to metabolite accumulation.
• Excretion: Renal (≈60 %) and biliary (≈30 %). Dose adjustment required in CKD (e.g., reduce or discontinue when eGFR <30 mL/min).

Indications

• Heart failure: In addition to ACE‑I/ARB therapy, 25–200 mg/day improves survival and reduces hospitalisation.
• Hypertension: Used as add‑on in resistant hypertension or hyperaldosteronism.
• Edema: Congestive, nephrotic, or gynecologic edema not responsive to loop diuretics.
• Hyperaldosteronism: Primary or secondary (e.g., Cushing’s).
• Hyperandrogenic disorders:
• Acne vulgaris, hirsutism, androgenetic alopecia, and polycystic ovary syndrome (PCOS).
• Congenital adrenal hyperplasia (late‑onset CAH).
• Other: Heart failure with preserved ejection fraction (HFpEF) at lower doses; use in some renal diseases to reduce albuminuria.

Contraindications

• Contraindications:
• Serum potassium >5.0 mmol/L.
• Severe renal impairment (eGFR <30 mL/min) unless closely monitored.
• Addison’s disease or acute adrenocortical insufficiency.
• Concurrent potassium‑sparing diuretic (e.g., amiloride) without monitoring.
• Warnings:
• Hyperkalemia: Monitor electrolytes; avoid in CKD or concurrent ACE‑I/ARB.
• Hypotension/orthostatic: Especially at initiation or dose escalations.
• Endocrine effects: Gynecomastia, menstrual irregularities, amenorrhea, precocious puberty.
• Liver function: Rare hepatotoxicity; check LFTs baseline and periodically.
• Drug interactions:
• CYP3A4 inhibitors may increase levels.
• Bile acid sequestrants may reduce oral bioavailability.
• Levothyroxine is absorbed less efficiently; monitor TSH.
• Pregnancy: Category C; risk of fetal masculinisation, especially in the first trimester. Use contraception.

Dosing

• Route: Oral capsule; most efficacious in divided doses.
• Timing: Administer in the evening to mitigate nocturnal sodium craving.
• Tapering: Gradual dose reduction over 1–2 weeks to prevent withdrawal hyperkalemia.

Adverse Effects

• Common (≥10 %)
• Gynecomastia, breast tenderness
• Menstrual irregularities (amenorrhea, spotting)
• Hyperkalemia (monitor)
• Gastro‑intestinal upset (nausea, vomiting, diarrhoea)
• Dizziness, orthostatic hypotension
• Headache
• Serious (≤1 %)
• Life‑threatening hyperkalemia (arrhythmia)
• Severe gynecomastia or breast cancer (rare)
• Hepatotoxicity (elevated transaminases)
• Acute interstitial nephritis
• Severe electrolyte disturbances (hypomagnesemia)
• Teratogenicity (fetal masculinisation); avoid in pregnancy

Monitoring

• Baseline:
• Serum electrolytes (K⁺, Na⁺, Cl⁻), creatinine, eGFR, BUN.
• Blood pressure, heart rate.
• LFTs (AST, ALT, ALP, bilirubin).
• TSH if on levothyroxine.
• Ongoing:
• K⁺ and BUN/Cr at 2–4 weeks after initiation or dose change, then every 3 months.
• BP daily until stable.
• LFTs every 6 months if chronic therapy.
• Monitor for signs of hyperandrogenism or feminisation.

Clinical Pearls

• Anti‑androgen advantage: Spironolactone is unique among potassium‑sparing diuretics; this property makes it an excellent first‑line agent for hirsutism and PCOS.
• ECG vigilance: Even modest elevations in K⁺ can prolong the QT interval; consider ECG when K⁺ >4.8 mmol/L.
• Drug–drug synergy: When combined with ACE‑I or ARB, the additive antimineralocorticoid effect can be therapeutic but also heightens hyperkalemia risk; start at lower doses and monitor aggressively.
• Timing of dose: Evening administration improves nocturnal sodium hunger and may reduce daytime sodium appetite.
• Metabolite monitoring: In patients with hepatic impairment, monitor both parent drug and canrenone levels when available, as canrenone is responsible for most of the long‑term effect.
• Menstrual disorders: In premenopausal women with severe menstrual bleeding, consider adding megestrol acetate or oral contraceptives to counteract hyperandrogenic side effects.
• Endocrine labs: Spironolactone can alter serum hormone levels; when interpreting testosterone, LH, or DHEA‑S, note the medication unless discontinuation is feasible.

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• *This drug card serves as a concise reference for medical students and clinicians. For patient‑specific counseling, always refer to the latest prescribing information and institutional guidelines.*