Sampine Mechanism of Action

Pharmacotherapeutic group: Selective calcium channel blockers with mainly vascular effects - Dihydropyridine derivatives. ATC Code: C08CA.
Pharmacology: Pharmacodynamics: S(-) Amlodipine is a pharmacologically active enantiomer of amlodipine. S(-) Amlodipine is an allosteric modulator and acts on the L-type of calcium channels. Receptor binding studies have shown that out of the two forms only the (S)-enantiomer of amlodipine binds to and blocks L-type calcium channels whereas the (R)-enantiomer has no activity on these channels.
The mechanism of the antihypertensive action of S(-) Amlodipine is due to a direct relaxant effect on vascular smooth muscle.
The precise mechanism by which S(-) Amlodipine relieves angina has not been fully determined but the following two actions play a role: 1. Decreases peripheral resistance by arteriolar vasodilatation leading to the reduction in oxygen requirement and energy consumption of cardiac smooth muscles.
2. Decreases coronary vascular resistance and can lead to an increase in coronary blood flow.
In patients with hypertension, once daily dosing provides clinically significant reductions of blood pressure (in both supine and standing positions) throughout the 24 hour interval.
In patients with angina, once daily administration of amlodipine increases total exercise time, the delay of occurrence of anginal attack and the delay of the occurrence of a 1-mm ST interval. Amlodipine decreases both angina attack frequency and glyceryl trinitrate tablet consumption.
Pharmacokinetics: Absorption/Distribution: Administration of S(-) Amlodipine (2.5 mg) as a single dose gives maximum plasma concentration (C_max) of 8.3 to 9.3 ng/mL in 2 to 3 hrs (T_max). S(-) Amlodipine shows approximately 93% plasma protein binding in hypertensive patients. The mean AUC_0-t value (t = 48 hrs) of S(-) Amlodipine tablets (2.5 mg) is 95±14 ng·hr/mL.
Metabolism/Elimination: S(-) Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. The plasma elimination half-life of S(-) Amlodipine has been found to be 31±13 hrs.