Amlodipine's Mechanism of Action as a Vasodilator
Yes, amlodipine is a potent peripheral and coronary vasodilator that acts directly on vascular smooth muscle to reduce peripheral vascular resistance and blood pressure. 1
Mechanism of Action
- Amlodipine is a dihydropyridine calcium channel blocker (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle 1
- It selectively inhibits calcium ion influx across cell membranes, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells 1
- Amlodipine acts as a peripheral arterial vasodilator that directly affects vascular smooth muscle, causing reduction in peripheral vascular resistance 1
- Among calcium channel blockers, nifedipine and amlodipine have the most pronounced peripheral arterial dilatory effects 2
Vasodilatory Properties
- Amlodipine produces vasodilation resulting in a reduction of both supine and standing blood pressures following therapeutic dosing 1
- It has high selectivity for vascular smooth muscle with potent vasodilatory effects and minimal impact on myocardial contractility or cardiac conduction 3
- The vasodilatory action is responsible for the most common side effects associated with amlodipine therapy, including peripheral edema and flushing 4
- Amlodipine blocks constriction and restores blood flow in coronary arteries and arterioles in response to various vasoconstrictive stimuli, making it effective for vasospastic angina 1
Pharmacodynamic Profile
- Amlodipine has a gradual onset of effect due to its slow rate of association and dissociation with the calcium channel receptor binding site 1
- It has a long duration of action with an elimination half-life of 36-45 hours, allowing for once-daily dosing 3, 5
- The gradual onset of action results in less reflex tachycardia compared to other dihydropyridines, with chronic oral administration not leading to clinically significant changes in heart rate 1, 6
- Amlodipine's antihypertensive effectiveness is maintained for at least 24 hours with once-daily dosing 1
Clinical Applications
- Amlodipine's vasodilatory properties make it effective for treating hypertension, chronic stable angina, and vasospastic angina 3
- For exertional angina, amlodipine reduces total peripheral resistance (afterload) and myocardial oxygen demand 1
- For vasospastic angina, its inhibition of coronary spasm is responsible for its effectiveness 1
- Amlodipine is well tolerated by patients with mild left ventricular dysfunction, unlike verapamil and diltiazem which should be avoided in patients with pulmonary edema or severe left ventricular dysfunction 2
Comparison to Other Calcium Channel Blockers
- Calcium channel blockers are classified as dihydropyridines (like amlodipine) or non-dihydropyridines (like diltiazem and verapamil) 2
- While all calcium channel blockers cause coronary vasodilation, they vary in their effects on peripheral vasodilation, myocardial contractility, and cardiac conduction 2
- Amlodipine is considered more potent and longer-acting compared to newer calcium channel blockers 7
- Unlike verapamil and diltiazem, which have prominent effects on AV node and sinus node, amlodipine has few or no AV or sinus node effects 2
Cautions and Considerations
- Rapid-release, short-acting dihydropyridines (e.g., nifedipine) should be avoided without concomitant beta-blockade due to increased adverse potential 2
- Calcium channel blockers, including amlodipine, do not improve survival in patients with chronic stable angina with or without myocardial infarction 2
- In patients with erythromelalgia, calcium channel blockers may worsen symptoms, and discontinuation has resulted in symptom resolution in several patients 2