Generic Name

prodrug

Mechanism

• Enalapril is hydrolyzed in vivo to the active metabolite enalaprilat.
• Enalaprilat competitively inhibits ACE, the enzyme that converts angiotensin‑I to the vasoconstrictor angiotensin‑II.
• By reducing ANG‑II levels, it:
• Lowers systemic vascular resistance and arterial pressure;
• Decreases aldosterone secretion, causing natriuresis and diuresis;
• Attenuates sympathetic drive, improving heart‑failure outcomes.

Pharmacokinetics

• Absorption: Oral bioavailability ~30 % (limited by first‑pass metabolism).
• Onset: Peak plasma concentration ~2–3 h after dosing.
• Metabolism: Hydrolyzed in the liver to form enalaprilat (active).
• Elimination: Primarily renally excreted (∼90 % unchanged).
• Half‑life: ~9 h (enalaprilat) → allows twice‑daily dosing.
• Drug‑Drug Interactions: Concomitant use with potassium‑sparing diuretics, ACE inhibitors, ARBs, NSAIDs, or lithium can potentiate hyperkalemia or renal dysfunction.

Indications

• Hypertension: All‑stage therapy, often as part of a multi‑agent regimen.
• Chronic heart failure: ≥NYHA class II with reduced ejection fraction; improves survival.
• Post‑MI: Reduces mortality when initiated ≤48 h after uncomplicated MI.
• Diabetic nephropathy: Slows progression of proteinuria and renal decline.

Contraindications

• Absolute contraindications:
• Prior hypersensitivity to Enalapril or other ACE inhibitors;
• Pregnancy (any trimester);
• History of angioedema related to ACE inhibitor therapy.
• Relative contraindications:
• Severe renal insufficiency (CrCl < 30 mL/min) → consider dose reduction;
• Hyperkalemia, hypovolemia, or hyponatremia.
• Warnings:
• Monitor renal function and serum electrolytes;
• Be vigilant for signs of acute lung injury (pulmonary edema) especially in heart‑failure patients.

Dosing

• Administration: Take with or immediately after meals to reduce GI upset.
• Missed dose: Skip if >12 h until next dose; do not double.

Adverse Effects

Common (≥5 %)
• Dry cough, dizziness, GI irritation, headache.

Serious (≤1 %)
• Angioedema, hyperkalemia, acute kidney injury, hypotension, electrolyte imbalance, elevated serum creatinine, “ACE‑inhibitor cough rupture” → laryngospasm (rare).

Monitoring

• Baseline: Serum creatinine, BUN, potassium, electrolytes; BP; eGFR.
• Post‑initiation:
• 1–2 weeks: Repeat creatinine, potassium, BP.
• Every 3–6 months thereafter: Renal function, electrolytes, albuminuria.
• During dose escalation: Watch for orthostatic hypotension, especially in frail patients.

Clinical Pearls

• "Dry cough" is a hallmark of ACE‑inhibitors: If persistent >3 weeks, switch to an ARB (e.g., losartan) at an equivalent dose.
• Angioedema risk is highest within the first 2 weeks; any facial or tongue edema warrants immediate discontinuation.
• Potassium‑sparing diuretics + ACEI → add a potassium‑monitoring lab at 1 week.
• NSAIDs blunt ACE‑inhibitor renal protection: avoid or co‑prescribe a loop diuretic in patients requiring NSAIDs.
• Post‑MI continuation: If blood pressure ≤90 / 60 mm Hg, switch to a lower dose or another antihypertensive (e.g., dihydropyridine Ca‑channel blocker) while closely monitoring.
• Renal dose adjustment: Reduce to 5 mg BID if CrCl < 30 mL/min; consider 2.5 mg BID if CrCl 15–30 mL/min.

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• Enalapril remains a cornerstone in cardiovascular therapy, balancing efficacy with a predictable safety profile when monitoring indices are adhered to.