Pharmacology
ACE inhibitors & ARBs
Pharmacology

ACE inhibitors & ARBs

First-line in HFrEF, post-MI, CKD with proteinuria, HTN with DM. Know the kidney and the cough.

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◆Mechanism

  • •ACE-I (-pril: lisinopril, enalapril, captopril): block ACE → ↓ angiotensin II + ↑ bradykinin (responsible for cough/angioedema)
  • •ARBs (-sartan: losartan, valsartan, candesartan): block AT1 receptor → no bradykinin effect → no cough; lower angioedema risk
  • •ARNI (sacubitril-valsartan): adds neprilysin inhibition → ↑ natriuretic peptides; first-line for HFrEF NYHA II–III

◆Indications

  • •HTN with DM or proteinuria (renal-protective)
  • •HFrEF (mortality benefit)
  • •Post-MI (esp. with reduced EF)
  • •Diabetic nephropathy (microalbuminuria)
  • •Non-diabetic CKD with proteinuria

◆Side effects

  • •Dry cough (ACE-I only) — 10–20%, weeks to months after start; switch to ARB
  • •Angioedema (ACE-I > ARB; higher in Black patients) — discontinue immediately, do NOT switch within class without caution
  • •Hyperkalemia (be careful with K-sparing diuretics, NSAIDs, K supplements)
  • •Acute kidney injury — esp. with bilateral renal artery stenosis or volume depletion
  • •First-dose hypotension (esp. in volume-depleted patients)
  • •PREGNANCY CATEGORY X: oligohydramnios, fetal renal failure, skull defects, hypotension

◆Monitoring

  • •Check BMP within 1–2 weeks of starting or dose change
  • •Expect Cr rise up to 30% (acceptable due to ↓ intraglomerular pressure)
  • •Hold if Cr rises >30%, K >5.5, or symptomatic hypotension

High-yield pearls

  • ◆ACE-I + ARB combo = MORE harm than benefit (hyperK, AKI, hypotension); never combine
  • ◆Bilateral renal artery stenosis on ACE-I → AKI; classic vignette: HTN + flash pulmonary edema + asymmetric kidneys
  • ◆Pregnant patient on ACE-I → STOP immediately, switch to labetalol/methyldopa/nifedipine
  • ◆ARB tolerance better than ACE-I for cough; if angioedema with ACE-I, ARBs are USUALLY but not always safe
  • ◆Sacubitril-valsartan: 36-hr washout from ACE-I before starting (combined = high angioedema risk)
Quick check

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