Introduction
Captopril is an orally active angiotensin-converting enzyme (ACE) inhibitor that represents a cornerstone in the management of hypertension, heart failure, and certain renal conditions. As the first commercially available ACE inhibitor, it has been extensively studied and remains widely used in clinical practice despite the development of newer agents in its class.
Mechanism of Action
Captopril competitively inhibits angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II—a potent vasoconstrictor. This inhibition results in:
- Decreased angiotensin II production
- Reduced vasoconstriction and peripheral vascular resistance
- Decreased aldosterone secretion, leading to reduced sodium and water retention
- Increased bradykinin levels, contributing to vasodilation
These combined effects produce a reduction in blood pressure and afterload, making it particularly beneficial in heart failure management.
Indications
- Hypertension (monotherapy or combination therapy)
- Heart failure (NYHA Class II-IV)
- Post-myocardial infarction with left ventricular dysfunction (ejection fraction ≤40%)
- Diabetic nephropathy (type 1 diabetes with proteinuria >500 mg/day)
- Scleroderma renal crisis
Dosage and Administration
Hypertension: Initial dose 25 mg BID or TID; maintenance 25-150 mg BID or TID Heart failure: Initial dose 6.25-12.5 mg TID; target dose 50-100 mg TID Post-MI: Initial dose 6.25 mg, then 12.5 mg TID, increasing to 50 mg TID Diabetic nephropathy: 25 mg TID Special Populations:- Renal impairment: Reduce dose (CrCl <40 mL/min)
- Elderly: Start with lower doses
- Hepatic impairment: Caution recommended
Pharmacokinetics
Absorption: Rapidly absorbed (60-75% bioavailability), food reduces absorption by 30-40% Distribution: Volume of distribution 0.7 L/kg, protein binding 25-30% Metabolism: Hepatic metabolism minimal; forms disulfide metabolites Elimination: Half-life 2-3 hours; primarily renal excretion (95%) Onset: 15-30 minutes; Peak effect: 1-1.5 hours; Duration: 6-12 hoursContraindications
- History of angioedema related to previous ACE inhibitor treatment
- Hypersensitivity to captopril or any component
- Concomitant use with aliskiren in patients with diabetes
- Pregnancy (second and third trimesters)
Warnings and Precautions
Black Box Warnings:- Fetal toxicity: Can cause injury and death to developing fetus
- Angioedema: May occur at any time during treatment
- Neutropenia/Agranulocytosis: More common in patients with renal impairment or collagen vascular diseases
- Hypotension: Especially in volume-depleted patients
- Hyperkalemia: Monitor potassium levels
- Renal function impairment: May cause acute renal failure
- Cough: Characteristic dry, persistent cough
- Surgery/anesthesia: May potentiate hypotension
Drug Interactions
Significant Interactions:- Diuretics: Enhanced hypotensive effect
- NSAIDs: May reduce antihypertensive effect
- Potassium-sparing diuretics/potassium supplements: Increased hyperkalemia risk
- Lithium: Increased lithium levels
- Gold therapy: Nitritoid reactions reported
- Allopurinol: Increased risk of hypersensitivity reactions
Adverse Effects
Common (>10%): Cough, taste disturbance, rash, hypotension Less Common (1-10%): Hyperkalemia, dizziness, fatigue, nausea Rare (<1%): Angioedema, neutropenia, proteinuria, hepatic dysfunction Serious: Renal failure, angioedema, agranulocytosis, hepatotoxicityMonitoring Parameters
- Blood pressure (standing and supine)
- Renal function (serum creatinine, BUN)
- Electrolytes (potassium)
- CBC with differential (especially in high-risk patients)
- Urinalysis for proteinuria
- Signs of angioedema
- Fetal monitoring in women of childbearing potential
Patient Education
- Take on empty stomach 1 hour before meals
- Report any swelling of face, lips, tongue, or difficulty breathing immediately
- Persistent dry cough may occur
- Rise slowly from sitting/lying position to avoid dizziness
- Regular blood pressure monitoring important
- Maintain adequate hydration unless contraindicated
- Avoid potassium supplements unless prescribed
- Use effective contraception; notify provider immediately if pregnancy suspected
- Do not stop medication abruptly without medical supervision
References
1. FDA Prescribing Information: Captopril Tablets 2. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) 3. ACC/AHA Heart Failure Guidelines (2017) 4. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. 5. McKeage K, Goa KL. Captopril: A review of its pharmacology and therapeutic efficacy after myocardial infarction and in ischaemic heart disease. Drugs & Aging. 1995. 6. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993.
Note: This information is for educational purposes only and does not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.