Captopril
Captopril
Generic Name
Captopril
Mechanism
- Inhibits ACE, blocking conversion of angiotensin I → angiotensin II.
- Reduces angiotensin‑II–mediated vasoconstriction and aldosterone secretion, decreasing peripheral resistance and sodium‑water retention.
- Prevents bradykinin degradation, elevating bradykinin levels → vasodilation, natriuresis, and improved renal perfusion.
- Net effect: ↓ arterial pressure, ↓ afterload, ↓ neurohormonal activation, and cardiorenal protection.
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Pharmacokinetics
| Parameter | Approximate Value |
| Absorption | Oral ~70% bioavailability; peak plasma 1–2 h. |
| Distribution | Plasma protein binding ~0–3 % (unbound). |
| Metabolism | Minimal; active metabolites via CYP2C9 for > 90 % renal excretion. |
| Elimination | Renally excreted (≈70 % unchanged). Half‑life ~2 h (shorter in renal impairment). |
| Special Populations | Doses reduced in CKD; careful in pregnancy (category D). |
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Indications
- Hypertension—monotherapy or combination.
- Heart failure (NYHA II–IV) with reduced ejection fraction.
- Post‑myocardial infarction—reduces remodeling.
- Diabetic nephropathy—slows progression of proteinuria.
- Left ventricular hypertrophy—reduces LV wall thickness.
- Renal protection in hypertension/diabetes (especially when using concomitant ACEI‑related BP‑control).
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Contraindications
| Category | Key Points |
| Absolute Contraindications | |
| 1. History of angioedema related to ACE inhibition. | |
| 2. Pregnancy (serious fetal harm). | |
| 3. Concomitant use with ARB (serious bradykinin‑related edema). | |
| Relative Contraindications | |
| 1. Severe renal dysfunction (CrCl 5.5 mmol/L). | |
| 3. Severe hepatic disease. | |
| Warnings | |
| 1. Hypotension, syncope. | |
| 2. Bradykinin‑mediated angioedema, especially in African‑American or post‑c-section women. | |
| 3. Hyperkalemia risk ↑ with NSAIDs, ACE inhibitors, potassium‑sparing diuretics. | |
| Drug Interactions | |
| 1. NSAIDs → ↓ renin activity & ACEI efficacy; ↑ creatinine. | |
| 2. Diuretics (especially thiazides) → synergistic BP drop. | |
| 3. Potassium‑sparing diuretics, K‑supplementation → hyperkalemia. |
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Dosing
| Status | Adults | Elderly (≥65 yr) | CKD (CrCl 30–59 mL/min) |
| Oral tablet | 25 mg BID → titrate to 50 mg BID (max 150 mg/day). | Start 12.5 mg BID; titrate as tolerated. | Start 6.25 mg BID; titrate cautiously. |
| Enteral suspension | 12.5–25 mg BID. | Similar to tablets, but lower starting dose. | Use only if oral absorption questionable; monitor creatinine closely. |
| Intravenous (for acute settings) | 2.5 mg IV bolus, then 5 mg q6h as needed; max 20 mg/day. | Reduce load → 5–10 mg q6h; monitor BP closely. | Avoid unless essential; renal clearance poor. |
*Key Tips*: Initiate at lowest dose; allow 2–4 weeks per titration step; maintain 24‑h dosing interval for stable BP.
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Adverse Effects
| Category | Events |
| Common | Cough (dry, persistent, ~10–15 %); nasal congestion; mild hyperkalemia. |
| Moderate | Fatigue, dizziness, mild edema, hypotension, gastrointestinal upset. |
| Serious | Angioedema (facial/neck swelling, airway obstruction), marked hyperkalemia (>5.5 mmol/L), severe hypotension, renal impairment (creatinine rise >30 % from baseline). |
*Monitoring*: Watch for cough changes → possible ACEI‑related edema; stop if cough resolves or if angioedema occurs.
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Monitoring
| Parameter | Target | Frequency |
| Blood pressure & pulse | Aim 130/80 mmHg (or guideline‑specific). | Every visit until stable. |
| Serum creatinine & eGFR | ≤30 % rise from baseline. | Every 1–3 months initially; then annually. |
| Serum potassium | 3.5–5.0 mmol/L (or 3.5–4.5 mmol/L with concomitant diuretics). | Baseline, 1 week after initiation, then monthly. |
| Urinalysis | Proteinuria (≥1+) | Every 3–6 months in diabetic nephropathy. |
| Liver function tests | Within normal limits. | Baseline, then annually. |
| Signs of angioedema | None. | Patient education; immediate phone if swelling. |
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Clinical Pearls
- Captopril’s sulfhydryl group → *chemosensitizes angioedema*; risk higher in African‑Americans and post‑pregnancy women.
- In hypertensive emergencies, captopril IV provides a *rapid, moderate** BP drop* without the dramatic effect of hydralazine.
- Start captopril *after* diuretics to avoid excessive volume depletion; sequence matters for BP control.
- The short plasma half‑life makes captopril less likely to maintain 24‑h BP control—but it’s *good for dosing flexibility* (dose adjustments without long‑term consequences).
- Be vigilant for bradykinin‑mediated cough: if cough resolves, consider switching to a newer ACE inhibitor with a higher likelihood of discontinuation.
- Drug–drug interactions with beta‑blockers can mask hypoglycemia in diabetic patients; monitor glucose closely.
- Renal‑protective benefits: in diabetic nephropathy, captopril combined with strict glucose control reduces proteinuria by >50 % compared with placebo.
- For *elderly patients*, captopril is often better tolerated than newer ACE inhibitors due to its *lower incidence of cough*.
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• References (for further reading)
1. Goodman & Gilman's The Pharmacological Basis of Therapeutics (Latest Edition).
2. Braunwald’s Heart Disease (17th edition).
3. KDIGO Clinical Practice Guideline for the Management of Diabetic Kidney Disease (2023 update).