What is pharmacology and how should I select an appropriate antihypertensive medication for an adult patient?

Selecting Antihypertensive Medications for Adult Patients

What is Pharmacology?

Pharmacology is the science studying how drugs interact with the body through absorption, distribution, metabolism, and excretion (ADME), and how the body responds to drugs through receptor interactions and physiological effects. 1, 2 These principles determine drug concentration at target sites, therapeutic efficacy, and adverse effects. 3

When to Initiate Antihypertensive Therapy

Start pharmacological treatment immediately for any adult with BP ≥140/90 mmHg, or BP ≥130/80 mmHg if they have established cardiovascular disease, diabetes, chronic kidney disease, or 10-year ASCVD risk ≥10%. 4, 5

• For Stage 1 hypertension (130-139/80-89 mmHg) without high-risk conditions, attempt lifestyle modifications for 3-6 months before medication. 5
• For BP ≥140/90 mmHg or high-risk patients with BP ≥130/80 mmHg, initiate medication immediately alongside lifestyle changes. 6, 4

First-Line Medication Selection

Choose from four equally effective first-line drug classes: thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, or long-acting dihydropyridine calcium channel blockers—all reduce cardiovascular morbidity and mortality equivalently. 6, 5

Specific Drug Class Selection Based on Comorbidities:

• Heart failure with reduced ejection fraction: ACE inhibitor or ARB plus beta-blocker 6
• Post-myocardial infarction: ACE inhibitor or ARB plus beta-blocker 6
• Chronic kidney disease: ACE inhibitor or ARB (provides renoprotection) 6
• Diabetes mellitus: ACE inhibitor or ARB (first choice) 5
• Black patients without CKD: Thiazide diuretic or calcium channel blocker (more effective than ACE inhibitors/ARBs in this population) 6
• Older adults (≥65 years): Thiazide diuretic or calcium channel blocker 6

Critical Contraindications to Avoid:

• Never prescribe ACE inhibitors or ARBs to pregnant patients or those of childbearing potential without reliable contraception (teratogenic). 5
• Avoid ACE inhibitors in bilateral renal artery stenosis, severe hyperkalemia, or severe sodium depletion. 4

Combination Therapy Strategy

For patients with BP ≥160/100 mmHg (Grade 2-3 hypertension) or high cardiovascular risk, initiate combination therapy immediately, preferably as a single-pill combination to improve adherence. 6, 4

Recommended Two-Drug Combinations:

• Thiazide diuretic + ACE inhibitor 6
• Thiazide diuretic + ARB 6
• Calcium channel blocker + ACE inhibitor 6
• Calcium channel blocker + ARB 6
• Calcium channel blocker + thiazide diuretic 6

Combinations to NEVER Use:

Never combine ACE inhibitor with ARB—this increases cardiovascular and renal risk without additional benefit. 6, 5

• Never combine two drugs from the same class (e.g., two different beta-blockers). 6
• Exception: Different diuretic classes can be combined (thiazide + potassium-sparing + loop diuretic). 6

Blood Pressure Targets

Target BP <130/80 mmHg for patients with known cardiovascular disease or 10-year ASCVD risk ≥10%. 6, 4

• For patients without CVD or high risk: Target <140/90 mmHg (strong recommendation) or consider <130/80 mmHg (reasonable). 6
• For adults ≥65 years: Target systolic BP <130 mmHg if tolerated; <150 mmHg is acceptable for those ≥60 years without high-risk conditions. 5
• For high-risk patients (diabetes, CKD, high CVD risk): Target <130/80 mmHg. 6, 4

Medication Titration Protocol

Titrate medications every 2-4 weeks until BP target is achieved, with the goal of reaching target within 3 months. 5

• Reassess BP 7-14 days after medication initiation or dose changes. 5
• If BP remains above goal on two-drug combination, advance to triple therapy with ACE inhibitor or ARB + calcium channel blocker + thiazide-like diuretic as a single-pill combination. 5

Critical Monitoring Requirements

Monitor serum creatinine and potassium within 7-14 days after initiating or titrating ACE inhibitors, ARBs, or diuretics, then at least annually. 5

• Accept creatinine increases up to 30% from baseline after starting RAS blockers—this reflects beneficial reduction in intraglomerular pressure, not harm. 5
• If creatinine increases >30% or potassium >5.5 mEq/L, reduce dose or discontinue. 5

Follow-Up Schedule

Follow up monthly after medication initiation or changes until BP is at target, then every 3-6 months once controlled. 6, 5

Strategies to Maximize Adherence

Prescribe single-pill combination medications when multiple drugs are needed—this dramatically improves adherence compared to separate pills. 6, 5

• Prescribe 90-day refills instead of 30-day supplies when allowed. 5
• Implement team-based care with pharmacists and nurses for medication management. 5
• Utilize home BP monitoring with telehealth follow-up. 5

Resistant Hypertension Management

Resistant hypertension is defined as uncontrolled BP despite three medications (including a diuretic) or controlled BP requiring ≥4 medications. 6

• Common three-drug regimen: Calcium channel blocker + ACE inhibitor or ARB + chlorthalidone (long-acting thiazide-like diuretic). 6
• Add spironolactone (mineralocorticoid receptor antagonist) as the fourth agent—substantial evidence demonstrates superior BP reduction compared to other fourth-line options. 6
• Before diagnosing resistant hypertension, confirm medication adherence, rule out white-coat effect with ambulatory BP monitoring, and screen for secondary causes. 6