enalapril

MECHANISM: Enalapril is a prodrug hydrolyzed by hepatic esterases to enalaprilat (active; the IV form). Inhibits angiotensin-converting enzyme (ACE, kininase II), which (1) decreases angiotensin II (less vasoconstriction, less aldosterone secretion, less efferent arteriole constriction) and (2) prevents bradykinin breakdown (raises bradykinin). Net effects: arterial and venous dilation (decreased preload and afterload), decreased Na+/water retention, increased renin (loss of negative feedback), increased K+ retention, and dilation of the efferent arteriole (decreased GFR and decreased intraglomerular pressure).

INDICATIONS: Hypertension; heart failure with reduced EF (mortality benefit, e.g., SOLVD trial); post-MI (prevents ventricular remodeling); diabetic nephropathy and proteinuric CKD (renoprotective by lowering intraglomerular pressure, slows progression of albuminuria); asymptomatic LV dysfunction.

ADVERSE EFFECTS (mnemonic CAPTOPRIL): Cough (bradykinin/substance P), Angioedema (bradykinin-mediated, not IgE; higher risk in Black patients; contraindicated with history of ACEi angioedema, and C1 esterase inhibitor deficiency is a concern), Proteinuria (rare), Taste changes (dysgeusia; more classically captopril), hypOtension (especially first dose, volume-depleted patients), Pregnancy contraindication (fetal renal malformations, oligohydramnios, pulmonary hypoplasia, skull hypoplasia, fetal/neonatal renal failure), Rash, Increased renin, Lower angiotensin II. Also hyperkalemia and acute kidney injury (GFR drop, especially with bilateral renal artery stenosis or stenosis in a solitary kidney, or volume depletion). Neutropenia is rare (more captopril).

CONTRAINDICATIONS/INTERACTIONS: Pregnancy; bilateral renal artery stenosis; history of ACEi angioedema; concurrent sacubitril (neprilysin inhibitor; do not use with ACEi due to angioedema risk; need 36-hour washout); caution with K+-sparing diuretics, K+ supplements, NSAIDs (risk of AKI/hyperkalemia), and aliskiren in diabetics. Avoid dual ACEi + ARB.

KEY BOARD POINTS: Lab findings: increased creatinine (expected small rise up to ~30% acceptable), increased K+, increased renin, decreased angiotensin II, and aldosterone decreased. If cough develops, switch to an ARB (e.g., losartan), which does not increase bradykinin; ARBs still carry the same fetal toxicity, hyperkalemia, and AKI risks but have much lower cough and angioedema rates. Unlike captopril and lisinopril, enalapril is a prodrug (captopril and lisinopril are active; lisinopril is also not metabolized). Enalapril has a longer half-life than captopril, allowing BID dosing (captopril is TID). ACE inhibitor suffix: "-pril." Contrast with ARBs ("-sartan"), which block the AT1 receptor and do not affect bradykinin.