Amlodipine onset
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Amlodipine Onset: Insights from Recent Research
Introduction to Amlodipine and Its Pharmacokinetics
Amlodipine is a third-generation dihydropyridine calcium antagonist known for its unique pharmacokinetic profile. It is characterized by almost complete absorption, late-peak plasma concentrations, high bioavailability, and slow hepatic biodegradation. These properties contribute to its slow onset of action and long duration of effect, making it suitable for once-daily dosing. The slow onset of action is beneficial as it minimizes reflex tachycardia and vasodilator side effects commonly associated with other dihydropyridines.
Onset of Action in Ischemic Conditions
In studies involving ischemia-induced myocardial conduction delay in anesthetized pigs, amlodipine demonstrated a significant reduction in the time to onset of conduction delay in the subendocardium during ischemic periods. This effect was observed after intravenous administration of amlodipine, indicating its rapid action in acute settings. Additionally, amlodipine increased regional myocardial blood flow in nonischemic myocardium and decreased mean aortic pressure without altering flow in the ischemic region, further supporting its efficacy in managing ischemic conditions.
Onset of Action in Angina Pectoris
Clinical trials have shown that amlodipine effectively increases the time to onset of angina in patients with stable exertional angina pectoris. This effect was observed at both 6 and 24 hours post-dose, indicating a sustained onset of action throughout the day. In another study, intravenous administration of amlodipine increased the time to pacing-induced angina from 6 to 8.2 minutes, demonstrating its rapid onset in acute angina management.
Comparative Studies and Exercise Tolerance
Comparative studies have highlighted amlodipine's efficacy in improving exercise tolerance and delaying the onset of angina. In a study comparing amlodipine with controlled-onset, extended-release verapamil and amlodipine plus atenolol, all treatments significantly improved exercise duration and time to moderate angina. However, amlodipine monotherapy resulted in a statistically significant increase in the total duration of ischemic episodes compared to placebo, whereas combination therapies were more effective in reducing ambulatory myocardial ischemia. This suggests that while amlodipine is effective on its own, its combination with other agents may enhance its therapeutic benefits.
Hemodynamic Effects and Safety Profile
Amlodipine's hemodynamic effects include a decrease in systemic vascular resistance and mean arterial pressure, with a slight increase in heart rate. These effects contribute to its antianginal efficacy without causing deleterious negative inotropic effects. The safety profile of amlodipine is favorable, with a low incidence of severe side effects compared to beta-blockers and other calcium antagonists. It is well tolerated by elderly patients and does not require dosage modifications in renal impairment.
Conclusion
Amlodipine exhibits a slow onset of action with sustained therapeutic effects, making it effective for once-daily dosing in the management of ischemic conditions and stable angina pectoris. Its unique pharmacokinetic properties, combined with a favorable safety profile, make it a valuable option in cardiovascular therapy. The drug's ability to improve exercise tolerance and delay the onset of angina further underscores its clinical benefits.
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