Introduction
Enalapril is an angiotensin-converting enzyme (ACE) inhibitor widely used in cardiovascular medicine. First approved by the FDA in 1985, it remains a cornerstone therapy for hypertension, heart failure, and certain renal conditions. As a prodrug, enalapril requires hepatic conversion to its active metabolite, enalaprilat, which provides sustained pharmacologic effects.
Mechanism of Action
Enalaprilat competitively inhibits angiotensin-converting enzyme (ACE), preventing the conversion of angiotensin I to angiotensin II—a potent vasoconstrictor. This results in:
- Decreased peripheral vascular resistance
- Reduced aldosterone secretion
- Diminished sodium and water retention
- Increased bradykinin levels (contributing to vasodilation but also to cough side effect)
Indications
FDA-approved indications:
- Hypertension (monotherapy or combination therapy)
- Heart failure with reduced ejection fraction
- Asymptomatic left ventricular dysfunction
Off-label uses:
- Diabetic nephropathy
- Chronic kidney disease proteinuria
- Secondary stroke prevention
Dosage and Administration
Hypertension:- Initial dose: 5 mg once daily
- Maintenance: 10-40 mg daily in 1-2 divided doses
- Initial: 2.5 mg once or twice daily
- Titrate to target dose of 10-20 mg twice daily
- Renal impairment: Reduce dose if CrCl <30 mL/min
- Geriatric: Start with lower initial dose (2.5 mg)
- Hepatic impairment: No specific adjustment needed
Pharmacokinetics
- Absorption: Oral bioavailability ~60% (not affected by food)
- Distribution: Protein binding ~50-60%, Vd: 1.7 L/kg
- Metabolism: Hepatic hydrolysis to active metabolite enalaprilat
- Elimination: Renal excretion (60% as enalaprilat, 20% as enalapril)
- Half-life: Enalapril: 2 hours; Enalaprilat: 11 hours
Contraindications
- History of angioedema related to previous ACE inhibitor treatment
- Hypersensitivity to enalapril or any component
- Concomitant use with aliskiren in patients with diabetes
- Second and third trimester of pregnancy
Warnings and Precautions
Black Box Warnings:- Fetal toxicity: Can cause injury and death to developing fetus
- Discontinue when pregnancy detected
- Angioedema: Monitor for facial, laryngeal, or intestinal swelling
- Hypotension: Risk increased in volume-depleted patients
- Hyperkalemia: Monitor potassium, especially with renal impairment
- Neutropenia/agranulocytosis: Rare but serious
- Renal impairment: May cause acute kidney injury
- Cough: Dry, persistent cough may develop
Drug Interactions
Significant interactions:- Diuretics: Enhanced hypotensive effect
- Lithium: Increased lithium levels and toxicity
- NSAIDs: Reduced antihypertensive effect, increased renal risk
- Potassium-sparing diuretics/potassium supplements: Increased hyperkalemia risk
- Aliskiren: Increased adverse effects in diabetic patients
- Gold injections: Nitritoid reactions reported
Adverse Effects
Common (≥1%):- Cough (5-20%)
- Dizziness (4-8%)
- Headache (2-5%)
- Fatigue (2-4%)
- Nausea (1-2%)
- Angioedema
- Acute renal failure
- Hyperkalemia
- Neutropenia/agranulocytosis
- Hepatic failure
- Stevens-Johnson syndrome
Monitoring Parameters
Baseline:- Blood pressure
- Renal function (BUN, creatinine, eGFR)
- Serum electrolytes (potassium, sodium)
- CBC with differential
- Blood pressure at each visit
- Renal function and potassium within 2-4 weeks of initiation/dose change
- Periodic monitoring of renal function and electrolytes
- Monitor for cough and angioedema symptoms
Patient Education
- Take at same time each day, with or without food
- Report any signs of infection (fever, sore throat)
- Notify provider immediately if swelling of face, lips, or difficulty breathing occurs
- Rise slowly from sitting/lying position to prevent dizziness
- Report persistent dry cough
- Avoid potassium supplements unless prescribed
- Use effective contraception; stop medication if pregnancy suspected
- Regular blood pressure monitoring
- Maintain adequate hydration unless contraindicated
References
1. FDA Prescribing Information: Vasotec (enalapril maleate) tablets 2. Joint National Committee 8 Evidence-Based Guideline for the Management of High Blood Pressure in Adults 3. ACCF/AHA Guideline for the Management of Heart Failure 4. KDIGO Clinical Practice Guideline for Blood Pressure Management in CKD 5. Micromedex Drug Information: Enalapril 6. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th Edition 7. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.