What is the onset of action of amlodipine (calcium channel blocker)?

Onset of Action of Amlodipine

Amlodipine begins working within 6-8 hours after administration, with gradual blood pressure reduction, but takes 7-10 days of daily dosing to reach full therapeutic effect. 1, 2

Pharmacokinetic Profile

• Amlodipine has a slow onset of action with peak plasma concentrations occurring 6-8 hours after oral administration 1
• The drug has high oral bioavailability (60-80%) and accumulates to steady-state with once-daily administration over a period of 1-1.5 weeks 1
• Amlodipine has a long elimination half-life of 40-60 hours, which contributes to its gradual onset and sustained effect 1, 3
• The gradual onset is due to both intermediate absorption rate and the physicochemical characteristics of the drug-cell membrane-receptor interaction 1

Pharmacodynamic Effects

• After a single dose, blood pressure decreases gradually over 4-8 hours and may slowly return to baseline over 24-72 hours 1
• Full therapeutic effect requires consistent daily dosing for approximately 7-10 days to reach steady-state plasma concentrations 1, 4
• Unlike some calcium channel blockers with rapid onset, amlodipine's gradual action prevents reflex tachycardia as physiological reflexes are not suddenly activated 1, 5
• During chronic once-daily dosing, blood pressure remains decreased from baseline with minimal fluctuation over the 24-hour dosing interval 1

Mechanism of Action

• Amlodipine is a dihydropyridine calcium channel blocker that inhibits calcium influx through "slow" channels in vascular smooth muscle cells 2
• It produces vasodilation in peripheral and coronary vascular beds, resulting in reduced peripheral vascular resistance and blood pressure 2
• The drug binds to both dihydropyridine and nondihydropyridine binding sites 2
• Amlodipine's interaction with calcium channels is characterized by gradual association and dissociation with receptor binding sites, contributing to its slow onset of action 2

Clinical Implications

• The gradual onset of action makes amlodipine suitable for chronic hypertension management but not for acute hypertensive crises 5
• When discontinuing amlodipine, blood pressure returns to baseline gradually over 7-10 days with no evidence of rebound hypertension 1
• Small fluctuations in plasma concentration between doses (20-25%) contribute to consistent blood pressure control throughout the day 1, 3
• Amlodipine's long half-life allows for once-daily dosing and provides protection even when occasional doses are missed 4

Special Considerations

• Age, severe hepatic impairment, and severe renal impairment may influence the pharmacokinetic profile, potentially leading to higher plasma concentrations and longer half-lives 3
• Dose-dependent blood pressure reductions have been observed with amlodipine, with higher doses (10 mg) achieving greater antihypertensive effects than lower doses (2.5-5 mg) 6
• Side effects such as edema, palpitations, dizziness, and flushing are more common with higher doses 4