ACE Inhibitors & ARBs
The AANP exam tests ACE inhibitors and ARBs harder than any other antihypertensive class because they sit at the intersection of hypertension, heart failure, chronic kidney disease, and diabetic renoprotection. ACE inhibitors block conversion of angiotensin I to angiotensin II; ARBs block the angiotensin II type-1 receptor directly. Both lower blood pressure, reduce afterload, slow proteinuric kidney decline, and improve mortality after MI and in HFrEF. The board angle is recognizing when to start one (diabetic with microalbuminuria, HFrEF, post-MI), when to stop one (pregnancy, acute kidney injury, hyperkalemia), and how to handle the dry cough that drives ACE-to-ARB switches.
📖 Overview
ACE inhibitors (lisinopril, ramipril, enalapril) block the enzyme that converts angiotensin I → angiotensin II. ARBs (losartan, valsartan) block the angiotensin II receptor directly. Both lower blood pressure, reduce cardiac remodeling after MI, slow progression of CHF, and are renoprotective in diabetes and proteinuric CKD. ARBs are the go-to substitute when an ACE inhibitor causes cough or angioedema.
⚙️ Mechanism of Action
Renin-angiotensin-aldosterone system (RAAS) blockade → vasodilation, decreased aldosterone, decreased sodium/water retention. Also increases bradykinin (ACEi only) — this is why they cause the dry cough.
💎 Board Pearls
- 🚨 Pregnancy = ABSOLUTE contraindication (teratogenic in all trimesters — fetal renal damage, oligohydramnios).
- ⚠️ Hyperkalemia — check K+ and creatinine within 1–2 weeks of starting or dose increase.
- 🔴 Angioedema = STOP immediately, never rechallenge (risk carries to ARBs, though less common).
- 💡 ACEi cough (up to 20%) is bradykinin-mediated → switch to ARB (no cough).
- 📈 Preferred first-line in: diabetes with proteinuria, CHF (mortality benefit), post-MI, CKD.
- 🚫 Avoid combining ACE + ARB + direct renin inhibitor (doubles AKI/hyperK risk, no added benefit).
💊 Drugs in This Class
- Lisinopril — Prinivil, ZestrilHTN, CHF, post-MI, diabetic nephropathy, proteinuric CKD.
- Ramipril — AltaceHTN, CHF post-MI, CV risk reduction in high-risk patients (HOPE trial).
- Losartan — CozaarHTN, CHF (ACE intolerant), diabetic nephropathy, gout-friendly HTN.
- Valsartan — DiovanHTN, post-MI with LV dysfunction, CHF. Combined with sacubitril (Entresto) for HFrEF.
Sources
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