Antihypertensive Drug Classes
A systematic review of the five major antihypertensive drug classes, their mechanisms, evidence base, and selection criteria.
## Overview
Hypertension affects over 1.2 billion adults worldwide and is the leading modifiable risk factor for cardiovascular death. Five first-line drug classes form the backbone of treatment, each targeting a different physiological pathway controlling blood pressure.
## ACE Inhibitors
Drugs like lisinopril, enalapril, and ramipril block angiotensin-converting enzyme, reducing angiotensin II production. This lowers peripheral resistance, decreases aldosterone secretion, and reduces cardiac remodeling. They are first-choice agents for patients with heart failure, diabetes, or chronic kidney disease. The most common side effect is a dry cough (5-20% of patients) caused by bradykinin accumulation. Angioedema is rare but potentially life-threatening.
## Angiotensin Receptor Blockers
Losartan, valsartan, and candesartan block AT1 receptors directly. They produce similar hemodynamic effects to ACE inhibitors without the cough, since bradykinin metabolism is unaffected. ARBs are preferred when ACE inhibitor cough is intolerable. Combined use of ACE inhibitors and ARBs is generally not recommended due to hyperkalemia risk without added benefit.
## Calcium Channel Blockers
Dihydropyridines (amlodipine, nifedipine) preferentially relax vascular smooth muscle, lowering peripheral resistance. Non-dihydropyridines (verapamil, diltiazem) additionally reduce heart rate and contractility. Amlodipine is among the most prescribed antihypertensives globally due to its long half-life and consistent efficacy across populations. Pedal edema is the main dose-limiting side effect.
## Thiazide and Thiazide-Like Diuretics
Hydrochlorothiazide, chlorthalidone, and indapamide inhibit sodium reabsorption in the distal convoluted tubule. Beyond acute diuresis, long-term blood pressure reduction involves decreased peripheral vascular resistance. Chlorthalidone has stronger outcome data than hydrochlorothiazide. Metabolic effects include hypokalemia, hyperuricemia, and modest glucose elevation.
## Beta-Blockers
Metoprolol, bisoprolol, and carvedilol reduce heart rate and cardiac output. Current guidelines position them as add-on therapy for uncomplicated hypertension but first-line when concurrent heart failure, angina, or rate control is needed. Cardioselective agents (beta-1 selective) are preferred to avoid bronchospasm.
## Selection Strategy
Initial choice depends on comorbidities, demographics, and tolerability. Combination therapy with two agents from different classes is first-line for stage 2 hypertension (BP >= 160/100). Single-pill combinations improve adherence. Target blood pressure is generally <130/80 mmHg.
## Key Takeaways
- Five first-line classes target different BP-regulating pathways
- ACE inhibitors and ARBs are preferred with diabetes or CKD
- Most patients require two or more agents for adequate control
- Selection should be individualized by comorbidity and tolerability