Enalapril

BRAND NAMES

1. Vasotec (widely used in the United States) 

2. Renitec (common in Europe and many other countries) 

3. Enam (used in India and some regions).

MECHANISM OF ACTION

Enalapril is a prodrug that is converted in the liver to its active metabolite, enalaprilat, which inhibits the angiotensin-converting enzyme (ACE). This enzyme normally converts angiotensin I to angiotensin II, a potent vasoconstrictor. By blocking this conversion, enalapril reduces levels of angiotensin II, leading to vasodilation, decreased peripheral resistance, and lowered blood pressure.

PHARMACOKINETICS

Absorption

Enalapril is well absorbed after oral administration, with an approximate bioavailability of about 60%. Peak plasma concentrations of enalapril are typically reached within 1 hour, while its active metabolite, enalaprilat, reaches peak levels in about 3–4 hours.

Distribution

Enalapril is approximately 50–60% bound to plasma proteins, which facilitates its transport in circulation while allowing adequate tissue penetration, including into vascular and renal tissues where it exerts its therapeutic effects.

Metabolism

Enalapril is a prodrug that undergoes rapid hepatic metabolism to its active form, enalaprilat, primarily through hydrolysis. This conversion occurs mainly in the liver and is essential for its pharmacological activity, as enalaprilat is the compound responsible for ACE inhibition.

Elimination

Enalapril is eliminated primarily through the renal route, with both enalapril and its active metabolite, enalaprilat, excreted in the urine. Approximately 60% of the administered dose is recovered in urine, partly as unchanged enalaprilat and partly as enalapril.

PHARMACODYNAMICS

Enalapril exerts its pharmacodynamic effects through inhibition of the angiotensin-converting enzyme (ACE), leading to decreased formation of angiotensin II and reduced degradation of bradykinin. This results in vasodilation, decreased peripheral vascular resistance, and lowered blood pressure. The reduction in angiotensin II also decreases aldosterone secretion, promoting sodium and water excretion while conserving potassium.

ADMINISTRATION

Enalapril is administered orally in the form of tablets or oral solution, and in some cases as intravenous enalaprilat in hospital settings when oral therapy is not feasible. It can be taken with or without food, as food does not significantly affect its absorption. The dosing is typically once or twice daily, depending on the indication such as hypertension or heart failure.

DOSAGE AND STRENGTH

Enalapril is available in oral tablet strengths of 2.5 mg, 5 mg, 10 mg, and 20 mg, with dosing tailored according to the patient’s condition such as hypertension or heart failure. It may also be available as an oral solution in some regions (commonly 1 mg/mL) and as intravenous enalaprilat (1.25 mg/mL) for hospital use when oral administration is not possible.

DRUG INTERACTIONS

Enalapril has several important drug interactions primarily related to its effects on the renin–angiotensin–aldosterone system and potassium balance. Concomitant use with potassium-sparing diuretics (such as spironolactone, eplerenone, or amiloride) or potassium supplements can increase the risk of hyperkalemia. Use with other antihypertensive agents or diuretics may produce an additive blood pressure–lowering effect, increasing the risk of hypotension, especially after the first dose.

FOOD INTERACTIONS

Enalapril has no significant clinically relevant food interactions. It can be taken with or without food, as food does not meaningfully affect its absorption or overall bioavailability. However, patients are sometimes advised to take it consistently in the same manner each day (either always with food or always without) to maintain routine and improve adherence.

CONTRAINDICATIONS

Enalapril is contraindicated in patients with a known hypersensitivity to enalapril, other ACE inhibitors, or any component of the formulation. It is also contraindicated in individuals with a history of angioedema related to previous ACE inhibitor therapy or idiopathic angioedema, due to the risk of life-threatening recurrence. The drug should not be used during pregnancy, especially in the second and third trimesters, as it can cause fetal toxicity, including renal impairment, skull hypoplasia, and even fetal death.

SIDE EFFECTS

1. Dry persistent cough 

2. Dizziness 

3. Headache 

4. Fatigue 

5. Hypotension (especially first-dose effect) 

6. Hyperkalemia 

7. Increased serum creatinine / reduced renal function 

8. Nausea

OVER DOSAGE

Enalapril overdose primarily leads to excessive inhibition of the renin–angiotensin–aldosterone system, resulting in marked hypotension, which may progress to shock. Patients may also experience dizziness, weakness, syncope, and electrolyte disturbances such as hyperkalemia due to reduced aldosterone secretion.

TOXICITY

Enalapril toxicity occurs when excessive inhibition of the renin–angiotensin–aldosterone system leads to profound physiological disturbances. The most prominent manifestation is severe hypotension, which may progress to shock, dizziness, syncope, and organ hypoperfusion. Electrolyte imbalance, particularly hyperkalemia, is a major concern due to reduced aldosterone secretion, and it may lead to cardiac arrhythmias in severe cases.