Understanding Preload and Afterload
Before diving into amlodipine's specific actions, it's crucial to understand two fundamental concepts in cardiovascular physiology: preload and afterload. These terms describe the workload on the heart during the cardiac cycle.
- Preload: This refers to the initial stretching of the cardiac muscle cells before they contract. It is determined by the volume of blood filling the ventricle at the end of diastole (the relaxation phase). Think of it as the volume the heart has to manage before it pumps.
- Afterload: This is the force or resistance the heart must overcome to eject blood from the ventricle into the aorta and systemic circulation during systole (the contraction phase). It is largely determined by systemic vascular resistance (SVR) and arterial blood pressure. High afterload means the heart has to work harder to pump blood out.
Amlodipine's Mechanism of Action
Amlodipine is a dihydropyridine calcium channel blocker (CCB). It works by blocking L-type calcium channels, which inhibits calcium influx into vascular smooth muscle and cardiac muscle cells. Calcium is necessary for muscle contraction, so this blockage causes muscle relaxation. Amlodipine has a greater effect on vascular smooth muscle compared to cardiac muscle.
The Primary Effect: Afterload Reduction
Amlodipine's main effect is afterload reduction. It relaxes the smooth muscles in the walls of peripheral arteries, causing vasodilation (widening of blood vessels). This vasodilation lowers systemic vascular resistance (SVR), which is the primary determinant of afterload. By reducing the resistance the left ventricle pumps against, amlodipine lowers blood pressure and reduces the heart's oxygen demand, making it useful for hypertension and stable angina.
Effect on Preload
Amlodipine's impact on preload is generally considered minimal or indirect. Its main action is on arteries, not veins, which primarily influence preload. While calcium channel blockers may cause some reduction in left ventricular preload, amlodipine's most significant clinical effect is afterload reduction. Some studies show no change in pulmonary artery occluded pressure (a measure of preload) at rest after amlodipine administration.
Comparison with Other Antihypertensives
Different blood pressure medications have varying effects on preload and afterload.
| Medication Class | Primary Mechanism | Effect on Preload | Effect on Afterload | Example |
|---|---|---|---|---|
| Amlodipine (CCB) | Arterial vasodilation | Minimal to none | Significant Reduction | Norvasc |
| ACE Inhibitors | Block Angiotensin II formation | Moderate Reduction | Moderate Reduction | Lisinopril |
| Beta-Blockers | Block beta-receptors | Increase | Moderate Reduction | Metoprolol |
| Diuretics (Thiazides) | Increase salt & water excretion | Significant Reduction | Minimal | Hydrochlorothiazide |
| Nitrates | Venous vasodilation | Significant Reduction | Minimal to Moderate | Nitroglycerin |
Clinical Applications and Considerations
Amlodipine is used to treat hypertension, angina, and coronary artery disease. Its afterload-reducing effect makes it a key treatment for hypertension. Typical doses range from 2.5 mg to 10 mg daily. Common side effects include peripheral edema, dizziness, flushing, and headache. The edema is due to vasodilation affecting capillary pressure and doesn't usually improve with diuretics.
Conclusion
Amlodipine primarily reduces afterload by dilating peripheral arteries and decreasing systemic vascular resistance. This lowers blood pressure and reduces the heart's workload. While it has minor or indirect effects on preload, its main clinical benefit comes from its significant reduction of afterload.
For additional information, consult MedlinePlus from the U.S. National Library of Medicine: Amlodipine Information.
