What are the major classes of antihypertensive medications, including typical agents and their usual starting doses?

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Classification of Antihypertensive Medications

The major first-line antihypertensive drug classes are ACE inhibitors (ACEi), angiotensin receptor blockers (ARBs), dihydropyridine calcium channel blockers (CCBs), and thiazide or thiazide-like diuretics, with beta-blockers (BB) also considered first-line when compelling indications exist 1, 2.

Major Drug Classes and Mechanisms

First-Line Agents

Renin-Angiotensin System (RAS) Blockers:

  • ACE Inhibitors - Block conversion of angiotensin I to angiotensin II
  • ARBs - Block angiotensin II receptors directly
  • These should never be combined together (ACEi + ARB or either with aliskiren) as this increases cardiovascular disease, kidney disease, and hyperkalemia risk 1

Calcium Channel Blockers:

  • Dihydropyridine CCBs (e.g., amlodipine, nifedipine) - Primary vasodilators
  • Non-dihydropyridine CCBs (e.g., diltiazem, verapamil) - Also affect heart rate
  • These two CCB subtypes can be combined in selected patients for additional BP lowering 1

Diuretics:

  • Thiazide and thiazide-like diuretics - Reduce volume and peripheral resistance
  • Loop diuretics - Reserved for heart failure or advanced kidney disease
  • Potassium-sparing diuretics - Can be combined with thiazides 1

Beta-Blockers:

  • Considered first-line when compelling indications exist (heart failure, post-MI, atrial fibrillation)
  • Vasodilating beta-blockers (labetalol, carvedilol, nebivolol) preferred when used for BP lowering alone 2

Second-Line and Resistant Hypertension Agents

Mineralocorticoid Receptor Antagonists (MRAs):

  • Spironolactone - First choice for resistant hypertension (uncontrolled on triple therapy)
  • Eplerenone - Alternative if spironolactone not tolerated; requires higher dosing (50-200 mg) and may need twice-daily administration 2

Alpha-1 Adrenergic Blockers:

  • Peripheral alpha-1 blockers for additional BP control 3

Centrally Acting Agents:

  • Reserved for later-line therapy due to side effects 2, 3

Direct Vasodilators:

  • Hydralazine - Third or fourth-line option
  • Minoxidil - Only when all other agents fail due to multiple side effects 2

Treatment Algorithm Structure

Initial Therapy Selection

For Stage 2 Hypertension (≥20/10 mmHg above target):

  • Start with combination therapy using single-pill combinations (SPCs) containing two first-line agents 1, 2
  • SPCs improve adherence and reduce cardiovascular events compared to multiple separate pills 1
  • Typical combinations: RAS blocker + CCB, RAS blocker + diuretic, or CCB + diuretic

For Stage 1 Hypertension:

  • Stepped-care approach with single agent is reasonable, particularly in older adults or those with history of hypotension 1

Escalation Strategy

If uncontrolled on dual therapy:

  • Advance to triple combination: RAS blocker + CCB + thiazide diuretic 2

If uncontrolled on maximally tolerated triple therapy (resistant hypertension):

  1. First, assess adherence before adding fourth agent
  2. Add spironolactone as preferred fourth-line agent 2
  3. If spironolactone not tolerated: eplerenone, other MRA, or vasodilating beta-blocker 2
  4. Only after these fail: consider hydralazine, amiloride, triamterene, centrally acting agents, or alpha-blockers 2

Critical Contraindications and Pitfalls

Never combine:

  • Two RAS blockers together (ACEi + ARB, or either with aliskiren) 1
  • Two drugs from the same class (e.g., two different beta-blockers or two different dihydropyridine CCBs) 1

Exception combinations that ARE appropriate:

  • Thiazide + potassium-sparing diuretics
  • Thiazide + loop diuretics
  • Dihydropyridine + non-dihydropyridine CCBs (in selected patients) 1

Special population considerations:

  • Older adults and those with hypotension history: initiate carefully with stepped-care approach and monitor for orthostatic hypotension 1
  • Once-daily dosing improves adherence over multiple daily doses 1

References

3
Research

Antihypertensive drugs.

Pharmacological research, 2017

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