What is Amlodipine?
Amlodipine is a long-acting dihydropyridine calcium channel blocker that inhibits calcium ion influx into vascular smooth muscle, producing pronounced peripheral arterial vasodilation with minimal effects on cardiac conduction or contractility. 1
Mechanism of Action
Amlodipine works by blocking L-type calcium channels in vascular smooth muscle cells, preventing the transmembrane influx of calcium ions required for muscle contraction. 1 This selective inhibition has a greater effect on vascular smooth muscle than on cardiac muscle, distinguishing it from non-dihydropyridine calcium channel blockers. 1
The drug binds to both dihydropyridine and nondihydropyridine binding sites with a gradual rate of association and dissociation, resulting in a gradual onset of effect rather than rapid vasodilation. 1 This pharmacological profile minimizes reflex tachycardia and reduces the incidence of side effects like headache that are common with shorter-acting calcium antagonists. 2
Pharmacological Properties
Amlodipine produces the most marked peripheral arterial vasodilation among calcium channel blockers, with minimal effects on atrioventricular node function, sinus node function, or cardiac conduction. 3, 4
Key pharmacokinetic characteristics include:
- Elimination half-life of 36-60 hours, allowing true once-daily dosing with sustained 24-hour blood pressure control. 5, 6
- High oral bioavailability of 60-80% with slow absorption, reaching peak plasma concentrations 6-8 hours after dosing. 6
- Minimal fluctuation (20-25%) in plasma drug concentration between doses during once-daily administration. 6
- Gradual onset and offset of action, with blood pressure slowly returning to baseline over 7-10 days after discontinuation without rebound effect. 6
Clinical Indications
Amlodipine is FDA-approved for three primary indications: 1
Hypertension
Amlodipine relaxes blood vessels, allowing blood to flow more easily and lowering blood pressure through reduction in peripheral vascular resistance. 1 The American Heart Association identifies amlodipine as having the strongest evidence among calcium channel blockers for hypertension management, demonstrating equivalent or superior outcomes compared to other antihypertensive classes in major cardiovascular outcome trials. 7
Chronic Stable Angina (Exertional Angina)
Amlodipine reduces total peripheral resistance (afterload) and the rate-pressure product, thereby decreasing myocardial oxygen demand at any given level of exercise. 1 The drug provides effective 24-hour anti-anginal and anti-ischemic efficacy when dosed once daily. 2
Vasospastic Angina (Prinzmetal's or Variant Angina)
Amlodipine blocks constriction and restores blood flow in coronary arteries and arterioles in response to calcium, potassium, epinephrine, serotonin, and thromboxane A2. 1 The European Society of Cardiology identifies calcium channel blockers as the treatment of choice for vasospastic angina, with amlodipine blocking coronary artery constriction effectively. 7
Dosing
Standard dosing begins at 5 mg once daily, which can be increased to 10 mg once daily if needed to control symptoms. 1, 2 The medication can be taken with or without food, and timing consistency (such as with breakfast, dinner, or bedtime) improves adherence. 1
Clinical Advantages
Amlodipine demonstrated equivalent cardiovascular outcomes to thiazide diuretics and ACE inhibitors in the ALLHAT trial, with no significant differences in fatal coronary heart disease, nonfatal myocardial infarction, combined coronary outcomes, or all-cause mortality. 7
In the CAMELOT study, amlodipine treatment in patients with stable coronary artery disease and normal blood pressure tended to reduce the incidence of hard endpoints, though results were not statistically significant. 3
Important Clinical Considerations
Heart Failure Patients
Amlodipine should not be used as routine treatment in patients with heart failure with reduced ejection fraction (HFrEF), though it may be considered for concurrent hypertension or angina as it has neutral effects on morbidity and mortality. 4, 7 The American College of Cardiology recommends close monitoring for signs of worsening heart failure, including increased dyspnea, weight gain, or edema in patients taking amlodipine. 4
Combination Therapy
Amlodipine combines effectively with ACE inhibitors or ARBs, reducing edema and improving blood pressure control through complementary mechanisms. 7 When combining with beta-blockers, long-acting dihydropyridines like amlodipine are preferred over non-dihydropyridines to avoid excessive bradycardia or heart block. 7
Amlodipine should never be combined with non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in heart failure patients, as these agents cause myocardial depression. 4
Drug Interactions
NSAIDs should be avoided in patients taking amlodipine for hypertension, as they worsen blood pressure control and may precipitate heart failure. 4
Common Adverse Effects
The most common adverse effect is peripheral edema (swelling of legs or ankles). 1, 5 Other side effects include:
Amlodipine does not cause postural hypotension, reflex tachycardia, or cardiac conduction disturbances due to its gradual onset of action. 8, 6
Critical Safety Warning
Rarely, when first starting amlodipine or increasing the dose, patients may experience a heart attack or worsening angina. 1 If this occurs, immediate medical attention is required—either call a doctor right away or go directly to a hospital emergency room. 1
In cases of amlodipine overdose, calcium administration, vasopressors, and high-dose insulin therapy may be required for severe toxicity. 4