Onset of Action of Amlodipine
Amlodipine has a gradual onset of action, with blood pressure effects beginning within 2-4 hours after oral administration, but full therapeutic effects taking 7-10 days to develop due to its long half-life of 40-60 hours. 1, 2
Pharmacokinetic Profile
Amlodipine's onset of action is characterized by several key features:
- Initial effects: Blood pressure begins to decrease gradually over 4-8 hours after the first dose 2
- Peak plasma concentration: Occurs 6-8 hours after oral administration 2
- Steady state: Achieved after 7-10 days of once-daily dosing 2, 3
- Elimination half-life: 40-60 hours in patients with normal hepatic function (extends to 56 hours in hepatic impairment) 1, 2
The gradual onset of action is due to:
- Intermediate rate of drug absorption
- Gradual association and dissociation with calcium channel receptor binding sites
- Physicochemical properties of the drug-membrane-receptor interaction 1, 2
Clinical Implications of Gradual Onset
The gradual onset of amlodipine provides several clinical advantages:
- Avoidance of acute hypotension: Unlike some other calcium channel blockers, amlodipine's gradual onset minimizes the risk of symptomatic hypotension 1
- No reflex tachycardia: The slow onset prevents activation of physiological reflexes that would increase heart rate 2
- Smooth blood pressure control: During chronic once-daily dosing, blood pressure decreases from baseline with minimal fluctuation over the 24-hour dosing interval 2, 3
Dose-Response Relationship
The onset and magnitude of blood pressure reduction are dose-dependent:
- 2.5 mg: Minimum effective dose for hypertension 4
- 5-10 mg: Higher doses produce more substantial and consistent blood pressure reductions 4, 5
- Dose titration: When increasing dose, additional antihypertensive effects develop gradually over several days 4, 5
Comparison to Other Calcium Channel Blockers
Amlodipine's onset profile differs from other calcium channel blockers:
- Dihydropyridines: Short-acting agents like immediate-release nifedipine have rapid onset but shorter duration, potentially causing reflex tachycardia 6
- Non-dihydropyridines: Verapamil and diltiazem have more prominent effects on AV conduction and sinus node function with somewhat faster onset 6
Important Clinical Considerations
- Discontinuation: Effects gradually diminish over 7-10 days after stopping treatment, with no evidence of rebound hypertension 2
- Hepatic impairment: Slower elimination (half-life of 56 hours) requires more cautious titration 1
- Elderly patients: Lower starting doses recommended due to potentially slower clearance 1
The gradual onset of action makes amlodipine particularly suitable for chronic conditions like hypertension and stable angina, where abrupt hemodynamic changes are undesirable and consistent 24-hour control is beneficial 1, 7.