Cardiovascular · Medicine Class
Inhibition of angiotensin-converting enzyme (ACE)
ACE inhibitors block the conversion of angiotensin I to angiotensin II — a potent vasoconstrictor and aldosterone stimulator. This results in vasodilation, reduced sodium/water retention, decreased cardiac afterload, and reduced aldosterone-mediated fibrosis. ACE inhibitors also reduce bradykinin degradation (accumulation causes the characteristic dry cough) and have direct anti-fibrotic effects on the heart and kidneys independent of blood pressure lowering.
Lisinopril (Prinivil, Zestril)
Most prescribed ACE inhibitor. Once daily. Renally cleared — dose adjust for GFR <30. Not metabolized by CYP enzymes.
Enalapril (Vasotec)
Prodrug (active: enalaprilat). IV form available. Classic trial medicine (SOLVD, CONSENSUS) proving HF mortality benefit.
Ramipril (Altace)
HOPE trial: reduced CV events 22% in high-risk patients without HF. Tissue ACE inhibitor with cardioprotective effect.
Benazepril (Lotensin)
Once daily. Often combined with amlodipine (Lotrel) for BP control.
Fosinopril (Monopril)
Dual elimination (renal + hepatic) — preferred in renal impairment; less dose adjustment needed.
Captopril (Capoten)
Shortest-acting ACE inhibitor (TID dosing). Used in hypertensive urgency (sublingual). First ACE inhibitor approved (1981).
Potassium supplements and K+-sparing diuretics (spironolactone) → hyperkalemia
NSAIDs → reduce antihypertensive effect; worsen renal function
Aliskiren → dual RAAS blockade; increased renal/hyperkalemia risk; contraindicated in diabetes
ARBs — dual RAAS blockade generally avoided except in HF with reduced EF
Lithium → ACE inhibitors reduce renal lithium clearance → lithium toxicity
Yes. ACE inhibitors (and ARBs) reduce intraglomerular pressure, decrease proteinuria, and slow progression of diabetic nephropathy independent of blood pressure effects. They are preferred first-line antihypertensives in all diabetic patients with proteinuria or any degree of CKD. Expected creatinine rise of <30% after initiation is acceptable and expected.
ACE breaks down bradykinin — a mediator of airway inflammation and the cough reflex. When ACE is inhibited, bradykinin accumulates in the lungs and triggers a persistent dry cough. This is a class effect affecting 10-20% of patients. The cough typically begins weeks to months after starting therapy and resolves within 1-4 weeks of stopping. Switching to an ARB (which does not affect bradykinin) eliminates the cough.