What medications are used to treat hypertension and what causes it?

Hypertension: Medications and Causes

Medications for Treating Hypertension

First-line antihypertensive therapy should consist of thiazide or thiazide-like diuretics (such as chlorthalidone or hydrochlorothiazide), ACE inhibitors or ARBs (such as lisinopril or candesartan), and calcium channel blockers (such as amlodipine). 1, 2, 3

Initial Drug Selection

• Thiazide diuretics (chlorthalidone, hydrochlorothiazide) are recommended as first-line agents and have been shown to reduce cardiovascular events in multiple large trials 1, 4
• ACE inhibitors (lisinopril, enalapril) or ARBs (candesartan, valsartan) are equally effective first-line options, particularly beneficial in patients with diabetes, chronic kidney disease, or heart failure 1, 3
• Calcium channel blockers (amlodipine, diltiazem) are appropriate first-line agents, especially effective in African American populations 1, 2
• Beta-blockers are NOT recommended as initial therapy for uncomplicated hypertension unless specific cardiovascular comorbidities exist (prior MI, heart failure, angina) 1

Combination Therapy Strategy

• Most patients require 2 or more drugs to achieve blood pressure control 1, 4
• Initial combination therapy is recommended for Stage 2 hypertension (BP ≥140/90 mmHg or ≥20/10 mmHg above target) 1
• Single-pill combinations improve adherence and should be strongly favored 1
• Preferred combinations include: ACE inhibitor or ARB + CCB, ACE inhibitor or ARB + thiazide diuretic, or CCB + thiazide diuretic 1
• Never combine ACE inhibitor + ARB + renin inhibitor—this is potentially harmful 1

Treatment Targets

• Target BP is <130/80 mmHg for most adults under 65 years 1, 4
• For adults ≥65 years, target SBP <130 mmHg 1
• For patients with diabetes or chronic kidney disease, target remains <130/80 mmHg 1

Resistant Hypertension Management

When BP remains uncontrolled on 3 drugs including a diuretic:

• Add low-dose spironolactone (25-50 mg daily) as the fourth-line agent 1, 5
• If spironolactone is not tolerated, consider eplerenone, amiloride, higher-dose thiazide, or loop diuretic 1
• Alternatively, add bisoprolol or doxazosin 1

Causes of Hypertension

Primary (Essential) Hypertension

Approximately 90% of hypertension cases are primary/essential hypertension with no single identifiable cause. 1, 6

The pathophysiology involves:

• Complex interactions between environmental factors, behavioral factors, and genetic predisposition 1, 6
• Dysregulation of multiple organ systems: renal, cardiovascular, and central nervous system 1, 6
• Hormonal network dysfunction: particularly the renin-angiotensin-aldosterone system 1, 6
• Vascular and immune mechanisms contributing to arterial stiffness and increased peripheral resistance 1, 6

Secondary Hypertension

An estimated 10-20% of hypertension has an identifiable secondary cause, though modern systematic screening suggests this may be substantially higher. 1

Common secondary causes include:

• Renal disease: chronic kidney disease, renovascular disease 1, 6
• Endocrine disorders: primary aldosteronism, pheochromocytoma, Cushing's syndrome, thyroid disorders 1
• Obstructive sleep apnea 1, 6
• Coarctation of the aorta 6
• Drug-induced hypertension: NSAIDs (increase BP by 3/1 mmHg), combined oral contraceptives (increase BP by 6/3 mmHg with high-dose estrogen), SNRIs and tricyclic antidepressants, steroids, sympathomimetics 1, 7

Modifiable Risk Factors

• Excess dietary sodium intake 1, 4
• Obesity and sedentary lifestyle 1, 4
• Excessive alcohol consumption (>2 drinks/day for men, >1 drink/day for women) 1, 4
• Low dietary potassium intake 4, 6

Important Clinical Pitfall

In patients presenting with malignant hypertension or hypertensive emergencies, secondary causes are found in 20-40% of cases, making thorough diagnostic workup essential. 1