Why is amlodipine used to treat hypertension?

Amlodipine for Hypertension Treatment

Amlodipine is a first-line antihypertensive agent that effectively lowers blood pressure by inhibiting calcium influx into vascular smooth muscle cells, resulting in vasodilation and reduced peripheral vascular resistance. 1

Mechanism of Action

• Amlodipine is a dihydropyridine calcium channel blocker that selectively inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle 1
• It has a greater effect on vascular smooth muscle cells than on cardiac muscle cells, producing vasodilation that reduces peripheral vascular resistance and blood pressure 1
• The long half-life (35-50 hours) and duration of action allows for once-daily dosing with sustained 24-hour blood pressure control 2

Clinical Efficacy

• Amlodipine effectively reduces both systolic and diastolic blood pressure, with dose-dependent effects starting at 2.5 mg and optimal effects typically seen at 5-10 mg daily 3
• In the ALLHAT trial, amlodipine was equally effective as chlorthalidone (a thiazide diuretic) in preventing coronary heart disease mortality and morbidity 4
• In the ASCOT trial, amlodipine-based therapy demonstrated superiority over atenolol-based therapy in reducing stroke and mortality 4
• The Anglo-Scandinavian Cardiac Outcomes Trial showed that amlodipine-based therapy (with perindopril added as needed) reduced the incidence of fatal and nonfatal strokes by 25% compared to atenolol-based therapy in diabetic patients 4

Advantages in Special Populations

• Amlodipine is effective in patients with diabetes, showing significant cardiovascular event reduction in this high-risk population 4
• It is particularly useful in elderly patients due to its ability to control blood pressure and protect against stroke and myocardial infarction 2
• In heart failure patients with persistent hypertension despite treatment with ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, amlodipine is recommended as a step 3 agent 4

Combination Therapy

• Amlodipine works effectively in combination with other antihypertensive agents, including ACE inhibitors, ARBs, beta-blockers, and thiazide diuretics 5
• The ACCOMPLISH trial demonstrated that the combination of an ACE inhibitor with amlodipine was superior to an ACE inhibitor with hydrochlorothiazide in reducing cardiovascular events in high-risk hypertensive patients 6
• In the ALLHAT study, many patients required multiple drugs to achieve blood pressure control, highlighting the importance of combination therapy in managing hypertension 4

Safety Profile

• Amlodipine is generally well-tolerated with a favorable safety profile 3
• Common side effects include peripheral edema, headache, flushing, and dizziness 1
• Unlike some calcium channel blockers (diltiazem and verapamil), amlodipine does not have significant negative inotropic effects at therapeutic doses 1
• Amlodipine does not significantly alter heart rate or electrocardiographic parameters when used alone or in combination with beta-blockers 1

Clinical Considerations and Caveats

• Starting dose is typically 5 mg once daily, with adjustment to 10 mg if necessary for blood pressure control 5
• Amlodipine can be taken with or without food, making it convenient for patient adherence 1
• The long half-life provides a forgiving pharmacokinetic profile, maintaining blood pressure control even if a dose is occasionally missed 2
• While amlodipine is effective for hypertension, negatively inotropic CCBs (diltiazem and verapamil) should not be used to treat hypertension in patients with heart failure with reduced ejection fraction 4

Outcomes Benefits

• Lowering blood pressure with amlodipine reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions 1
• In the VALUE trial, amlodipine was compared to valsartan and showed similar efficacy in preventing cardiac events and death 4
• The drug's ability to reduce blood pressure variability may contribute to its cardiovascular protective effects beyond simple blood pressure reduction 2

In conclusion, amlodipine is a highly effective antihypertensive agent with proven benefits for cardiovascular outcomes, making it an excellent choice for first-line treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents.