ACE inhibitor

Mechanism: ACE inhibitors block the enzyme that converts angiotensin I to angiotensin II in the lungs and other tissues. This reduces angiotensin II-mediated vasoconstriction and aldosterone secretion, leading to decreased blood pressure, reduced sodium/water retention, and decreased cardiac afterload/preload. Because ACE is identical to kininase II, ACE inhibition also prevents bradykinin degradation, contributing to vasodilation but also causing the characteristic dry cough and angioedema.

Clinical uses: Hypertension (especially with diabetes or CKD due to renoprotective effects), heart failure with reduced ejection fraction (reduces mortality via afterload/preload reduction and anti-remodeling effects), post-myocardial infarction (reduces remodeling and improves survival), diabetic nephropathy and proteinuric CKD (dilates efferent arteriole more than afferent, reducing intraglomerular pressure and proteinuria).

Adverse effects: Dry, nonproductive cough (bradykinin/substance P accumulation), hyperkalemia (decreased aldosterone), acute kidney injury especially in bilateral renal artery stenosis (loss of angiotensin II-mediated efferent arteriolar constriction needed to maintain GFR), angioedema (more common in African Americans, can be life-threatening if involves airway), hypotension (especially first-dose), teratogenic (fetal renal damage, oligohydramnios, skull ossification defects) - contraindicated in pregnancy.

Contraindications: Pregnancy, bilateral renal artery stenosis, history of angioedema, hyperkalemia.

Key associations for boards: Compare with ARBs (angiotensin receptor blockers, e.g., losartan) which block AT1 receptors directly and do NOT cause cough or angioedema (no bradykinin accumulation) because they don't affect bradykinin metabolism. ACE inhibitors are renoprotective in diabetics by reducing intraglomerular pressure via efferent arteriolar dilation. Remember: ACE inhibitors increase renin (loss of negative feedback) but decrease angiotensin II and aldosterone.