Usage
- Enalapril is prescribed for hypertension (high blood pressure), congestive heart failure, asymptomatic left ventricular dysfunction (a weakened heart muscle), and diabetic nephropathy (kidney damage caused by diabetes). It is also used to improve survival after a heart attack.
- Pharmacological classification: Angiotensin-Converting Enzyme (ACE) inhibitor.
- Mechanism of Action: Enalapril inhibits the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor that also stimulates aldosterone secretion. By blocking this conversion, enalapril causes vasodilation (widening of blood vessels), reduces blood volume, and decreases blood pressure.
Alternate Names
- Generic Name: Enalapril maleate
- Brand Names: Vasotec, Epaned
How It Works
- Pharmacodynamics: Enalapril’s primary effect is the reduction of blood pressure through vasodilation and decreased blood volume. It also reduces afterload (the resistance the heart has to pump against) and preload (the volume of blood in the heart at the end of diastole), improving cardiac output.
- Pharmacokinetics:
- Absorption: Orally administered enalapril is rapidly absorbed, reaching peak plasma concentrations within 1 hour. Food does not significantly affect absorption.
- Metabolism: Enalapril is a prodrug, meaning it is metabolized in the liver to its active form, enalaprilat.
- Elimination: Primarily eliminated via the kidneys, both as enalapril and enalaprilat.
- Mode of Action: Enalapril competitively inhibits ACE, preventing the conversion of angiotensin I to angiotensin II. This reduces angiotensin II-mediated vasoconstriction and aldosterone secretion.
- Receptor Binding/Enzyme Inhibition: Enalapril acts by directly inhibiting the ACE enzyme.
- Elimination Pathways: Renal excretion is the primary route, with some hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose: 5 mg orally once daily. Maintenance dose: 10-40 mg/day, administered as a single dose or in two divided doses. Maximum dose: 40 mg/day.
- Heart Failure: Initial dose: 2.5 mg orally twice daily. Titrate upwards as tolerated to a maximum of 40 mg/day, usually given in two divided doses.
- Asymptomatic Left Ventricular Dysfunction: Initial dose: 2.5 mg orally twice daily. Titrate as tolerated to a maximum of 20 mg/day, usually given in two divided doses.
Children (1 month and older):
- Hypertension: Initial dose: 0.08 mg/kg/day (up to 5 mg), given orally once daily or in two divided doses. May increase every 2 weeks as needed, not to exceed 0.58 mg/kg/day or 40 mg/day.
- Children younger than 1 month of age: Use is not recommended.
Special Cases:
- Elderly Patients: Start at a lower dose (2.5 mg daily) and titrate cautiously, as elderly patients are more susceptible to hypotension and renal impairment.
- Patients with Renal Impairment: Initial dose 2.5 mg daily. Adjust dose based on creatinine clearance; avoid in severe renal impairment (CrCl < 10 mL/min).
- Patients with Hepatic Dysfunction: Use cautiously; no specific dosage adjustments are provided, but close monitoring is recommended.
- Patients with Comorbid Conditions: For patients with diabetes and/or heart failure and renal impairment, careful titration is especially important.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Although Enalapril can be administered intravenously as enalaprilat (1.25 mg every 6 hours, titrated up to 5 mg every 6 hours), its primary use is in chronic conditions. Intravenous administration is more common in hypertensive crises. Specific dosing for these clinical settings should be based on patient stability and blood pressure control, titrated cautiously as needed.
Dosage Adjustments
- Renal Dysfunction: Dosage adjustments are crucial in renal impairment. Start with 2.5 mg daily and titrate based on response.
- Hepatic Dysfunction: Use with caution and monitor closely.
- Other conditions: Dosage adjustments may be needed for other conditions affecting drug clearance.
Side Effects
Common Side Effects
- Dizziness, lightheadedness, cough, hypotension, hyperkalemia, fatigue, headache, nausea, rash.
Rare but Serious Side Effects
- Angioedema (swelling of the face, lips, tongue, throat), acute kidney injury, severe hypotension.
Long-Term Effects
- Chronic kidney disease (with long-term use), electrolyte imbalances.
Adverse Drug Reactions (ADR)
- Angioedema, anaphylaxis, neutropenia (low white blood cell count), renal failure, hyperkalemia.
Contraindications
- Hypersensitivity to enalapril or other ACE inhibitors.
- History of angioedema related to ACE inhibitor use.
- Pregnancy (especially second and third trimesters).
- Bilateral renal artery stenosis (narrowing of the renal arteries).
- Concomitant use with sacubitril/valsartan.
Drug Interactions
- Diuretics: Increased risk of hypotension.
- Potassium-sparing diuretics (spironolactone, amiloride, triamterene), potassium supplements: Increased risk of hyperkalemia.
- NSAIDs (ibuprofen, naproxen): Reduced antihypertensive effect.
- Lithium: Increased lithium levels.
- Aliskiren (in patients with diabetes): Increased risk of hypotension, hyperkalemia, and renal impairment.
- Gold injections: May cause nitritoid reactions (flushing, nausea, vomiting).
- Sacubitril/valsartan: Increased risk of angioedema.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (positive evidence of human fetal risk). Contraindicated in the second and third trimesters.
- Fetal Risks: Fetal kidney damage, low amniotic fluid (oligohydramnios), skull ossification defects, neonatal hypotension, renal failure.
- Breastfeeding: Small amounts of enalapril are excreted in breast milk. Use is generally not recommended, especially in preterm infants or during the first few weeks after delivery.
Drug Profile Summary
- Mechanism of Action: ACE inhibitor.
- Side Effects: Dizziness, cough, hypotension, hyperkalemia, angioedema.
- Contraindications: Angioedema history, pregnancy, bilateral renal artery stenosis.
- Drug Interactions: Diuretics, potassium supplements, NSAIDs, lithium, aliskiren, sacubitril/valsartan.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy (second and third trimesters); use with caution during breastfeeding.
- Dosage: Highly variable; depends on indication and renal function.
- Monitoring Parameters: Blood pressure, renal function, potassium levels.
Popular Combinations
- Enalapril + Hydrochlorothiazide (a diuretic): This combination is commonly used to treat hypertension and heart failure, offering synergistic blood pressure reduction.
Precautions
- General Precautions: Monitor blood pressure, renal function, and potassium levels closely. Assess for signs of angioedema.
- Specific Populations:
- Pregnant Women: Avoid use, especially during the second and third trimesters.
- Breastfeeding Mothers: Use with caution and monitor the infant for side effects.
- Children & Elderly: Start at lower doses and titrate cautiously.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Enalapril?
A: The dosage is highly individualized and depends on the indication, renal function, and patient response. The starting dose for hypertension is typically 5 mg daily, while heart failure generally begins at 2.5 mg twice daily. Pediatric doses are weight-based.
Q2: What are the common side effects of Enalapril?
A: Common side effects include dizziness, lightheadedness, cough, hypotension, and hyperkalemia.
Q3: What are the serious side effects of Enalapril?
A: Serious side effects include angioedema (swelling of face, lips, tongue, or throat), severe hypotension, and renal failure.
Q4: Can Enalapril be used during pregnancy?
A: Enalapril is contraindicated during the second and third trimesters of pregnancy due to the risk of fetal harm.
Q5: Can Enalapril be used during breastfeeding?
A: Enalapril passes into breast milk in small amounts. Use is generally not recommended, especially with preterm infants.
Q6: What drugs interact with Enalapril?
A: Enalapril interacts with diuretics, potassium supplements, NSAIDs, lithium, aliskiren, and sacubitril/valsartan.
Q7: What should I monitor in patients taking Enalapril?
A: Closely monitor blood pressure, renal function (serum creatinine and potassium), and signs of angioedema.
Q8: How does Enalapril work?
A: Enalapril inhibits ACE, preventing the formation of angiotensin II, leading to vasodilation and decreased blood volume.
Q9: What are the contraindications to using Enalapril?
A: Contraindications include a history of angioedema related to ACE inhibitor use, pregnancy (second and third trimesters), bilateral renal artery stenosis, and concomitant use of sacubitril/valsartan.
Q10: What is the difference between Enalapril and Enalaprilat?
A: Enalapril is a prodrug that is converted to its active form, enalaprilat, in the liver. Enalaprilat can be administered intravenously.
