Enalapril
1. Drug Name
Generic Name: Enalapril
Brand Names: Vasotec, Enap, Epaned, and others
2. Drug Classification
Class: Antihypertensive, Angiotensin-Converting Enzyme (ACE) Inhibitor
Subclass: Dicarboxylate-containing ACE Inhibitor
3. Mechanism of Action
Enalapril works by inhibiting the enzyme angiotensin-converting enzyme (ACE), which converts angiotensin I to the active vasoconstrictor angiotensin II.
ACE Inhibition: By inhibiting ACE, enalapril reduces levels of angiotensin II, leading to vasodilation, reduced aldosterone secretion, and decreased reabsorption of sodium and water in the kidneys, resulting in reduced blood pressure.
Decreased Preload and Afterload: This reduction in angiotensin II decreases systemic vascular resistance and preload, thus lowering blood pressure and improving symptoms in heart failure.
Cardioprotective Effects: Long-term use helps prevent remodeling in the heart and blood vessels, providing protective effects in patients with hypertension and heart failure.
4. Pharmacokinetics
Absorption: Enalapril is well absorbed orally with a bioavailability of approximately 60%. It is converted to enalaprilat, its active metabolite, primarily in the liver.
Distribution: Enalapril has a volume of distribution (Vd) of about 1.0–1.5 L/kg. Enalaprilat is highly bound to plasma proteins.
Metabolism: Enalapril is a prodrug and is hydrolyzed in the liver to its active form, enalaprilat. This activation is necessary for the ACE inhibitory effect.
Excretion: Enalaprilat is eliminated primarily by the kidneys. The elimination half-life (t½) of enalaprilat is approximately 11 hours, with the drug excreted mainly in the urine, both as unchanged enalaprilat and enalapril.
Special Considerations: In patients with renal impairment, enalapril clearance is reduced, necessitating dose adjustments to avoid toxicity.
5. Indications
Primary Indications:
Hypertension: Enalapril is commonly used to treat high blood pressure, either as monotherapy or in combination with other antihypertensive agents.
Heart Failure: Used to reduce symptoms and mortality in patients with symptomatic heart failure.
Left Ventricular Dysfunction: To prevent the progression of heart failure in asymptomatic patients with left ventricular dysfunction.
Off-Label Uses:
Chronic Kidney Disease (CKD): Enalapril may be used to reduce proteinuria and slow disease progression in CKD.
Diabetic Nephropathy: Shown to help reduce proteinuria and protect kidney function in diabetic patients.
Specific Populations: Enalapril is suitable for adult populations but should be used cautiously in patients with kidney disease and in certain pediatric populations.
6. Dosage and Administration
Adult Dosing:
Hypertension: Initial dose of 5 mg orally once daily, with a typical maintenance dose of 10-40 mg/day, administered in single or divided doses.
Heart Failure: Initial dose of 2.5 mg once daily, titrated up to 20 mg/day based on response.
Left Ventricular Dysfunction: Starting dose of 2.5 mg twice daily, increased gradually to 10–20 mg twice daily as tolerated.
Pediatric Dosing: For children ≥1 month, the initial dose is 0.08 mg/kg once daily (up to a maximum starting dose of 5 mg), with adjustments based on clinical response.
Renal Impairment: Dosage should be reduced in patients with renal impairment. Patients with a creatinine clearance <30 mL/min may need an initial dose of 2.5 mg, with careful monitoring and dosage titration.
Maximum Safe Dose: The maximum recommended daily dose is 40 mg/day.
7. Contraindications
Absolute Contraindications:
History of angioedema associated with previous ACE inhibitor therapy.
Hereditary or idiopathic angioedema.
Pregnancy: Enalapril is contraindicated in pregnancy due to risks of fetal toxicity.
Hypersensitivity to enalapril or other ACE inhibitors.
Relative Contraindications:
Patients with a history of renal artery stenosis, as ACE inhibitors can worsen renal function in these individuals.
Severe hyperkalemia (potassium levels should be closely monitored).
8. Warnings and Precautions
Black Box Warnings:
Fetal Toxicity: Enalapril can cause injury or death to the developing fetus. It is contraindicated during pregnancy.
Special Warnings:
Angioedema: Enalapril can cause angioedema, a potentially life-threatening reaction. Patients should discontinue enalapril and seek medical help immediately if symptoms occur.
Hyperkalemia: Patients, especially those with renal impairment, diabetes, or those taking potassium-sparing diuretics, should be monitored for hyperkalemia.
Hypotension: Particularly in patients with heart failure or those who are volume-depleted.
Monitoring Parameters:
Monitor serum electrolytes, especially potassium.
Renal function tests, including serum creatinine and blood urea nitrogen (BUN), should be checked periodically.
Blood pressure should be regularly monitored to evaluate efficacy.
9. Adverse Effects
Common Adverse Effects:
Cough (persistent dry cough is common due to increased bradykinin levels)
Dizziness
Hypotension, particularly after the first dose
Less Common but Clinically Significant Side Effects:
Hyperkalemia, particularly in patients with renal impairment or those on potassium supplements.
Renal impairment or acute renal failure, especially in patients with renal artery stenosis.
Rare/Serious Adverse Reactions:
Angioedema (can affect the face, extremities, and respiratory tract)
Stevens-Johnson syndrome
Severe hypotension, especially in patients who are volume-depleted
10. Drug Interactions
Major Drug Interactions:
Potassium-Sparing Diuretics (e.g., spironolactone): Increases the risk of hyperkalemia.
NSAIDs: May reduce the antihypertensive effect of enalapril and increase the risk of renal dysfunction.
Lithium: Enalapril may increase lithium levels, leading to toxicity.
Diuretics: Co-administration with diuretics may lead to excessive hypotension.
Food-Drug Interactions:
Generally, enalapril can be taken with or without food; however, food may delay peak plasma concentrations slightly.
11. Clinical Pharmacology
Enalapril's ACE inhibitory action leads to vasodilation and decreased aldosterone production, resulting in lower blood pressure and reduced workload on the heart. It also causes an increase in bradykinin, which can contribute to both its beneficial and adverse effects, such as cough.
12. Special Populations
Pregnancy: Contraindicated due to fetal toxicity.
Lactation: Small amounts of enalapril are excreted in breast milk; use with caution.
Pediatrics: Safe for children over 1 month, with careful dose adjustment.
Geriatrics: May require dose adjustments due to age-related renal function decline.
13. Therapeutic Uses
First-Line Indications: Hypertension and heart failure.
Second-Line Indications: May be combined with other agents for further blood pressure control.
14. Monitoring and Follow-Up
Routine monitoring of renal function and electrolytes is recommended, especially potassium levels.
Blood pressure should be frequently monitored, particularly at treatment initiation and during dose changes.
15. Overdose Management
Symptoms of Overdose: Severe hypotension, hyperkalemia, renal failure.
Treatment Protocols: Supportive care includes intravenous fluids for hypotension. Hemodialysis can help remove enalapril from the blood if needed.
16. Patient Counseling Information
Adherence: Patients should take enalapril regularly and should not skip doses. They should be advised to avoid sudden cessation of therapy.
Signs of Angioedema: Patients should be informed to seek immediate medical attention if they experience symptoms of angioedema (e.g., swelling of the face, lips, or throat).
Avoid Potassium Supplements: Patients should avoid potassium supplements and salt substitutes containing potassium unless advised by their healthcare provider.
Pregnancy Warning: Women of childbearing age should be advised about the risks during pregnancy and to inform their healthcare provider if they become pregnant.