STEPTRACKERPHARMACOLOGY | CARDIOVASCULAR | HIGH-YIELD REVIEW

Antihypertensives

Five main classes lower blood pressure by cutting volume, resistance or the hormonal drive behind them — the right choice depends on the patient's other diseases.

FOCUS ON
First-line (most patients): thiazide, ACE inhibitor or ARB, dihydropyridine CCB. Compelling indications: diabetes with proteinuria or CKD → ACEi/ARB; HFrEF → ACEi/ARB/ARNI + β-blocker + MRA; post-MI → β-blocker + ACEi; Black patients without CKD → thiazide or CCB; pregnancy → labetalol, nifedipine, methyldopa, hydralazine; BPH → α1-blocker; osteoporosis → thiazide; migraine/tremor → propranolol. Hypertensive emergency (end-organ damage): IV labetalol, nicardipine, clevidipine, esmolol, nitroprusside (cyanide toxicity), fenoldopam (D1, ↑ renal flow); lower MAP ≤ 25% in the first hour. Avoid: ACEi/ARB in pregnancy and bilateral renal artery stenosis; β-blockers alone in cocaine; thiazides in gout; nondihydropyridines in HFrEF.
CLASS · DRUGS
MECHANISM
BEST FOR
KEY ADVERSE EFFECTS
Thiazides
HCTZ, chlorthalidone
Block NaCl cotransporter (DCT) → ↓ volume, later ↓ SVR
Most hypertension, osteoporosis, calcium stones
↓ K⁺, ↓ Na⁺, ↑ glucose, ↑ lipids, ↑ uric acid, ↑ Ca²⁺
ACE inhibitors
-pril
↓ Angiotensin II, ↑ bradykinin → efferent arteriole dilation
Diabetes, CKD with proteinuria, HFrEF, post-MI
Cough, angioedema, ↑ K⁺, ↑ creatinine, teratogenic
ARBs
-sartan
Block AT1 receptor
Same as ACEi; ACEi cough
↑ K⁺, ↑ creatinine, teratogenic; no cough
Dihydropyridine CCBs
amlodipine, nifedipine
Block L-type Ca²⁺ channels in vascular smooth muscle
Elderly, isolated systolic HTN, Black patients, Raynaud, pregnancy (nifedipine)
Peripheral edema, flushing, headache, reflex tachycardia, gingival hyperplasia
Nondihydropyridine CCBs
verapamil, diltiazem
Cardiac L-type channel block → ↓ HR and contractility
HTN with AF or angina
Bradycardia, AV block, constipation (verapamil); avoid in HFrEF
β-blockers
↓ HR, contractility, renin
Post-MI, HFrEF, AF, angina
Not first-line for uncomplicated HTN
Hydralazine
↑ cGMP → arteriolar dilation
Pregnancy, HFrEF with nitrates (Black patients)
Reflex tachycardia, fluid retention, drug-induced lupus (give with β-blocker + diuretic)
Minoxidil
Opens K⁺ channels → arteriolar hyperpolarization and dilation
Refractory HTN; topical for alopecia
Hypertrichosis, pericardial effusion, reflex tachycardia
Nitroprusside
Releases NO → ↑ cGMP; arterial + venous dilation
Hypertensive emergency, acute HF
Cyanide toxicity (treat with hydroxocobalamin, thiosulfate)
Fenoldopam
D1 agonist → arteriolar dilation, natriuresis
Hypertensive emergency with renal impairment
Hypotension, tachycardia, ↑ IOP
Clevidipine · nicardipine
IV dihydropyridines
Hypertensive emergency, perioperative
Clevidipine: lipid emulsion (avoid with egg/soy allergy)
Central α2 agonists
clonidine, methyldopa
↓ Sympathetic outflow
Pregnancy (methyldopa), adjunct
Rebound HTN, sedation, Coombs ⊕ (methyldopa)
Spironolactone · eplerenone
Aldosterone antagonist
Resistant HTN, primary hyperaldosteronism, HFrEF
↑ K⁺; spironolactone gynecomastia

Mechanism — why ACEi protect the diabetic kidney

Angiotensin II constricts efferent arteriole
→
ACEi/ARB dilate efferent
→
↓ Glomerular pressure↓ GFR slightly (creatinine rise up to 30% OK)
→
↓ Proteinuria, slower CKD

Matching drug to patient

PATIENT
FAVOR
AVOID
Diabetes + albuminuria
ACEi / ARB
—
Pregnancy
Labetalol, nifedipine
ACEi, ARB, aliskiren
Gout
Losartan, CCB
Thiazide, loop
Asthma
CCB, ACEi
Nonselective β-blocker
BPH
α1-blocker (add-on)
—

How it's tested

COMMON CONFUSIONA creatinine rise after starting an ACE inhibitor is expected up to ~30%; a larger jump suggests bilateral renal artery stenosis.
THE TRAPNever combine an ACE inhibitor with an ARB or aliskiren — more hyperkalemia and kidney injury, no benefit.
YOUR APPROACHComorbidity first → compelling-indication drug → check contraindications → watch electrolytes.

If you see… think…

Dry cough on a BP drug → ACE inhibitor (bradykinin) → switch to ARB
Lip and tongue swelling on lisinopril → angioedema (C1-INH normal)
Ankle edema on amlodipine → precapillary dilation
Lupus-like syndrome on a vasodilator → hydralazine
Excess hair growth → minoxidil
Confusion, lactic acidosis on IV vasodilator → nitroprusside cyanide toxicity
Gout flare after starting BP pill → thiazide (↑ uric acid)
Hypertensive emergency with renal failure → fenoldopam or nicardipine
Creatinine jumps after ACEi in an atherosclerotic patient → bilateral renal artery stenosis
Gingival hyperplasia → CCB (also phenytoin, cyclosporine)