angiotensin receptor blocker

**Mechanism:** ARBs competitively antagonize the angiotensin II type 1 (AT1) receptor (Gq-coupled) in vascular smooth muscle, adrenal cortex, kidney, and heart. Effects: (1) decreased vasoconstriction → lower systemic vascular resistance/afterload; (2) decreased aldosterone secretion → less Na+/water retention and less K+ excretion; (3) efferent arteriolar dilation → decreased intraglomerular pressure (renoprotective); (4) decreased cardiac and vascular remodeling. Unlike ACE inhibitors, ARBs do not inhibit ACE/kininase II, so bradykinin does not accumulate. Renin and angiotensin II levels rise (loss of negative feedback), and AT2 receptors remain unopposed (vasodilatory).

**Examples:** losartan (also weakly uricosuric; prodrug with active metabolite EXP3174), valsartan, candesartan, irbesartan, olmesartan, telmisartan, azilsartan. Suffix: -sartan. Sacubitril/valsartan (Entresto) combines an ARB with a neprilysin inhibitor for HFrEF.

**Indications:** - Hypertension - Heart failure with reduced EF (mortality benefit; use if ACEi not tolerated, or ARNI preferred) - Post-MI with LV dysfunction - Diabetic nephropathy / proteinuric CKD (slows progression) - Marfan syndrome (losartan reduces TGF-β signaling and aortic root dilation) - Stroke prevention in some high-risk patients

**Adverse effects:** - Hyperkalemia - Hypotension - Acute kidney injury/increased creatinine (esp. bilateral renal artery stenosis or solitary kidney stenosis, volume depletion) - Fetal toxicity (oligohydramnios, renal agenesis/dysgenesis, pulmonary hypoplasia, skull hypoplasia, death) → contraindicated in pregnancy (Boxed warning) - Angioedema is rare (much less than ACEi); no dry cough

**ARB vs. ACE inhibitor (high-yield comparison):** - Cough/angioedema: ACEi yes (↑ bradykinin); ARB no/rare - Angiotensin II levels: ↓ with ACEi; ↑ with ARB - Renin: ↑ with both - Both: hyperkalemia, AKI in renal artery stenosis, teratogenic, reduce proteinuria, efferent arteriole dilation - Do not combine ACEi + ARB routinely (increased hyperkalemia, AKI, hypotension without added benefit; ONTARGET trial)

**Clinical pearls:** Monitor creatinine and K+ 1–2 weeks after starting; a rise in creatinine <30% is acceptable. Avoid with potassium-sparing diuretics/K+ supplements and NSAIDs when possible. Switch from ACEi to ARB if the patient develops ACEi cough. If a patient has ACEi-induced angioedema, use ARBs cautiously.