Enalapril: A Comprehensive Overview

Enalapril is a widely prescribed angiotensin-converting enzyme (ACE) inhibitor used for the management of hypertension, heart failure, and certain kidney disorders. By inhibiting the conversion of angiotensin I to angiotensin II, it promotes vasodilation, leading to decreased vascular resistance and improved cardiac efficiency. Enalapril is available in oral and intravenous formulations, offering flexibility in clinical applications. Due to its well-documented efficacy, it remains a cornerstone in cardiovascular medicine and has been extensively studied for its long-term benefits in reducing morbidity and mortality in cardiovascular diseases.

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Uses of Enalapril

1. Hypertension

Enalapril is effective in reducing elevated blood pressure by diminishing systemic vascular resistance. It is particularly beneficial in patients with concomitant renal disease, as it mitigates the progression of hypertension-induced nephropathy. Clinical trials have demonstrated that enalapril significantly lowers the risk of stroke and myocardial infarction when used as part of an antihypertensive regimen.

2. Congestive Heart Failure (CHF)

Enalapril plays a crucial role in heart failure management by reducing afterload and preload, thus enhancing cardiac output. It alleviates symptoms such as dyspnoea, oedema, and fatigue, improving overall quality of life. Long-term studies indicate a reduction in hospitalisation rates and increased survival among CHF patients using enalapril.

3. Left Ventricular Dysfunction

Patients with asymptomatic left ventricular dysfunction benefit from enalapril therapy as it delays the progression to overt heart failure. The SOLVD (Studies of Left Ventricular Dysfunction) trial established its role in reducing the incidence of symptomatic heart failure in high-risk individuals.

4. Diabetic Nephropathy

Enalapril offers nephroprotection by reducing glomerular hypertension and proteinuria in diabetic patients. By modulating intraglomerular pressure, it slows the progression of diabetic kidney disease, making it a preferred agent for hypertensive diabetic patients.

Dosage and Administration

Standard Adult Dosage:

Hypertension: Initial dose: 5 mg once daily, titrated to 10-40 mg per day in one or two doses.
Heart Failure: Starting dose: 2.5 mg once daily, with gradual increments up to 20 mg per day based on tolerability.

Paediatric Dosage:

Children over 50 kg: Initial dose 2.5 mg once daily, adjusted according to response.
Enalapril is generally avoided in neonates due to limited safety data.

Dose Adjustments in Special Conditions

1. Renal Impairment

Enalapril is renally excreted, necessitating dose modifications in patients with renal dysfunction:

Creatinine clearance <30 mL/min: Initial dose should be reduced to 2.5 mg daily.
Dialysis patients: Enalapril should be administered with caution due to potential hypotension.

2. Hepatic Impairment

Enalapril undergoes hepatic bioactivation. Severe liver impairment may affect drug metabolism, warranting careful monitoring. Alternative agents should be considered in cases of advanced hepatic dysfunction.

3. Pregnancy and Lactation

Pregnancy: Enalapril is contraindicated in pregnancy due to teratogenic risks, particularly in the second and third trimesters.
Breastfeeding: It is excreted in breast milk in small quantities; therefore, caution is advised when prescribing to lactating mothers.

Effects and Side Effects

Therapeutic Benefits:

Lowered blood pressure
Improved cardiac function
Renal protection in hypertensive nephropathy
Reduced mortality in CHF patients

Common Adverse Effects:

Dizziness
Fatigue
Dry cough (ACE inhibitor-induced)
Hypotension
Hyperkalaemia

Severe Adverse Reactions:

Angioedema: Life-threatening swelling of the oropharyngeal region.
Renal failure: Worsening kidney function in susceptible individuals.
Severe hypotension: Particularly in volume-depleted patients.

Drug Combinations and Considerations

Commonly Used Combinations:

Diuretics (e.g., Thiazides): Enhances blood pressure control.
Beta-blockers (e.g., Carvedilol): Commonly used in CHF management.
Calcium Channel Blockers (e.g., Amlodipine): Provides additional antihypertensive efficacy.

Key Considerations During Infusion:

Monitor blood pressure closely to prevent excessive hypotension.
Assess renal function regularly.
Avoid concurrent use with potassium-sparing diuretics to prevent hyperkalaemia.

Presentation and Dosage Forms

Form	Strengths	Route
Tablets	2.5 mg, 5 mg, 10 mg, 20 mg	Oral
Oral Solution	1 mg/mL	Oral
Injectable (Enalaprilat)	1.25 mg/mL	IV

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Pharmacokinetics and Pharmacodynamics

Absorption: Well absorbed orally with peak plasma levels in 4 hours.
Metabolism: Prodrug converted to active enalaprilat in the liver.
Excretion: Primarily renal (60% unchanged drug).
Half-life: Approximately 11 hours.

Drug Interactions

Major Interactions:

NSAIDs: May reduce antihypertensive efficacy.
Potassium supplements: Increased risk of hyperkalaemia.
Lithium: Enhanced lithium toxicity.

Comparison with Other ACE Inhibitors

Drug	Half-life	Dosing Frequency	Special Features
Enalapril	11 hours	Once or twice daily	Prodrug activated in liver
Lisinopril	12 hours	Once daily	Not a prodrug
Ramipril	13-17 hours	Once daily	Preferred for CHF

Toxicity, Overdose, and Antidote

Overdose Symptoms:

Severe hypotension
Electrolyte imbalance
Renal dysfunction

Management:

IV fluids and vasopressors for hypotension
Dialysis may be required in severe toxicity

Recent Updates in 2025 Guidelines

Recent clinical trials confirm enalapril’s continued role in heart failure treatment. New guidelines advocate its combination with SGLT2 inhibitors for enhanced cardioprotective effects.

Key Facts to Remember

Enalapril is a first-line ACE inhibitor for hypertension and heart failure.
Contraindicated in pregnancy due to teratogenic effects.
Routine monitoring of renal function is essential.
Angioedema risk necessitates immediate medical intervention.

References

British National Formulary (BNF)
European Society of Cardiology (ESC) Guidelines
World Health Organization (WHO) Drug Index
National Health Service (NHS) Clinical Recommendations
PubMed – Enalapril Pharmacokinetics and Safety

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