Captopril is an angiotensin-converting enzyme (ACE) inhibitor used primarily in the management of hypertension and heart failure. It was the first ACE inhibitor developed and has a well-established role in cardiovascular therapeutics.
Indications
Captopril is indicated for:
Hypertension: As per the NICE guidelines, ACE inhibitors like captopril are recommended for patients under 55 years, especially with comorbid conditions.
Heart Failure: Reduces mortality and morbidity by decreasing afterload and preload.
Left Ventricular Dysfunction Post-Myocardial Infarction: Prevents remodeling of the heart.
Diabetic Nephropathy: Slows progression of kidney disease in patients with type 1 diabetes mellitus.
Proteinuria: Reduces protein excretion in chronic kidney disease.
Contraindications
Captopril should not be used in the following situations:
Contraindication
Explanation
Pregnancy
Teratogenic effects; can cause fetal injury or death.
History of Angioedema
Risk of recurrent angioedema, which can be life-threatening.
Bilateral Renal Artery Stenosis
Can lead to acute renal failure due to decreased glomerular filtration pressure.
Hyperkalemia
Risk of dangerously high potassium levels due to decreased aldosterone secretion.
Severe Renal Impairment
Reduced excretion can lead to accumulation and toxicity.
Pharmacodynamics
Captopril inhibits ACE, leading to decreased formation of angiotensin II and decreased degradation of bradykinin. This results in vasodilation, reduced aldosterone secretion, and decreased blood pressure.
Mechanism of Action
Liver releases
Angiotensinogen
Converted by Renin (from kidneys) to
Angiotensin I
Converted by ACE (from lungs) to
Angiotensin II
Captopril inhibits ACE here
Causes
Vasoconstriction
Stimulates Adrenal Cortex to release
Aldosterone
Increased Blood Pressure
Pharmacokinetics
Absorption
Well absorbed orally; bioavailability approximately 70% (reduced with food).
Volume of Distribution
Approximately 0.7 L/kg.
Protein Binding
About 25-30% bound to plasma proteins.
Metabolism
Partially metabolized to disulfide dimers and cysteine conjugates.
Elimination Route
Primarily excreted in urine (50% unchanged).
Half-Life
Approximately 2 hours (prolonged in renal impairment).
Clearance
Renal clearance; reduced in renal dysfunction.
Adverse Effects
Dry Cough: Due to accumulation of bradykinin.
Hyperkalemia: Reduced aldosterone leads to potassium retention.
Hypotension: Especially after the first dose; caution in volume-depleted patients.
Renal Impairment: Monitor renal function; risk in patients with renal artery stenosis.
Angioedema: Rare but serious; swelling of face, lips, tongue.
Rash and Taste Disturbances: Reversible upon discontinuation.
Drug Interactions
Potassium-Sparing Diuretics: Increased risk of hyperkalemia.
NSAIDs: May reduce antihypertensive effect and increase risk of renal impairment.
