Drugs Used to Treat Hypertension
The first-line drugs for hypertension treatment include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide or thiazide-like diuretics. 1, 2
First-Line Antihypertensive Medications
Renin-Angiotensin System (RAS) Blockers
- ACE inhibitors (e.g., lisinopril, perindopril) reduce blood pressure by inhibiting the conversion of angiotensin I to angiotensin II 3
- ARBs (e.g., valsartan, candesartan) block the binding of angiotensin II to its receptors 1
- Particularly beneficial for patients with diabetes, chronic kidney disease, heart failure, or previous myocardial infarction 1
- ACE inhibitors are recommended as first-line agents in most patients with diabetes 1
Calcium Channel Blockers (CCBs)
- Dihydropyridine CCBs (e.g., amlodipine) primarily affect vascular smooth muscle 1, 2
- Non-dihydropyridine CCBs (e.g., diltiazem, verapamil) affect both cardiac muscle and vascular smooth muscle 1
- Effective in all patient populations, particularly in Black patients 1, 4
- Often combined with RAS blockers for enhanced efficacy 4
Diuretics
- Thiazide and thiazide-like diuretics (e.g., hydrochlorothiazide, chlorthalidone, indapamide) are effective first-line agents 1
- Particularly effective in reducing cardiovascular events 1
- Loop diuretics (e.g., furosemide) are recommended when eGFR is <30 ml/min/1.73m² 1
- Thiazide-like diuretics with longer duration of action (chlorthalidone, indapamide) are preferred over hydrochlorothiazide 2
Beta-Blockers
- Not typically recommended as first-line agents except in specific conditions 1
- Indicated for patients with coronary artery disease, heart failure, or post-myocardial infarction 1
- Beta-1 selective agents are preferred in patients with COPD 1
Second-Line and Add-On Therapies
Mineralocorticoid Receptor Antagonists
- Spironolactone and eplerenone are effective add-on agents for resistant hypertension 1
- Particularly useful when added to a regimen that includes a RAS blocker, CCB, and diuretic 5
- Require monitoring of potassium and renal function, especially when combined with RAS blockers 5
Alpha-Blockers
- Used as add-on therapy when initial combinations are insufficient 2
- Effective for patients with benign prostatic hyperplasia 6
Direct Vasodilators
- Hydralazine and minoxidil are typically used as later-line agents 7
- Should be avoided in hypertensive emergencies 7
Combination Therapy
- Most patients require more than one drug to achieve blood pressure control 4, 2
- Preferred combinations include:
- Avoid combining two RAS blockers (ACE inhibitor + ARB) due to increased risk of adverse effects without additional benefit 4, 5
Special Populations
Chronic Kidney Disease
- RAS blockers are first-line due to their renoprotective effects 1
- Target BP <130/80 mmHg (<140/80 mmHg in elderly patients) 1
- Monitor eGFR, microalbuminuria, and electrolytes 1
Diabetes
- BP target <130/80 mmHg (<140/80 mmHg in elderly patients) 1
- Treatment strategy should include a RAS inhibitor plus a CCB and/or thiazide-like diuretic 1
- ACE inhibitors or ARBs are recommended first-line, especially with albuminuria 1
Coronary Artery Disease
- Beta-blockers are recommended, especially with prior MI 1
- ACE inhibitors are indicated if there is prior MI, LV dysfunction, diabetes, or CKD 1
Resistant Hypertension
- Defined as BP >140/90 mmHg despite three medications including a diuretic 1
- Add spironolactone as fourth agent if potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 5
- Verify medication adherence and rule out white coat hypertension 1, 5
Common Pitfalls to Avoid
- Combining two RAS blockers increases adverse effects without additional benefit 4
- Non-dihydropyridine CCBs should be used with caution in combination with beta-blockers due to risk of heart block 5
- Avoid abrupt cessation of beta-blockers as this can lead to rebound hypertension 5
- Be cautious with medications that may exacerbate hypertension (NSAIDs, oral contraceptives, steroids, etc.) 1