Felodipin-Natrapharm Mechanism of Action

Pharmacology: Pharmacodynamics: Felodipine is a calcium antagonist of the dihydropyridine class of calcium channel blockers. Calcium antagonist interfere with the voltage-dependent-L-type (slow) calcium channels in the plasma membranes of smooth muscle cells and reduce the inflow of calcium ions with the result of vasodilator. Felodipine is a vasoselective calcium antagonist, it has a much greater selectivity for vascular smooth muscle than for myocardial muscles. Felodipine selectively dilates arterioles with no effect on venous vessels.
Felodipine leads to a dose-related lowering blood pressure via vasodilatation and consequently a reduction of peripheral vascular resistance; it reduces both systolic and diastolic blood pressure. The hemodynamic effect of felodipine is accompanied by a reflex (baroreceptor-mediated) tachycardia. In therapeutic doses, felodipine has no direct effect on either cardiac contractility or cardiac conduction. Felodipine reduces renal vascular resistance. The glomerular filtration rate remains unchanged.
Pharmacokinetics: Felodipine is rapidly and completely absorbed following oral administration. Peak plasma levels are reached with the prolonged release formulation after 3-5 hrs. Constant levels are achieved approximately 3 days after starting treatment. Due to an extensive first-pass effect, only approximately 15% of the administered dose is systemically available.
The plasma protein-binding of felodipine is >99%. The volume of distribution is 10 L/kg, so that felodipine is rapidly distributed in extravascular tissue. Felodipine is extensively metabolized in the liver. No unchanged parent substance is detectable in the urine. The inactive hydrophilic metabolites formed by hepatic biotransformation are mainly eliminated renally (to approximately 70%) and the remainder is excreted in the feces. Felodipine is eliminated in several phases. Approximately 50% of the administered dose is excreted with a half-life (t_½) of 4 hrs and the mean terminal t_½ is 18 hrs. The mean plasma clearance is 1,100 mL/L and depends on the hepatic blood flow. Elevated plasma concentrations have been measured in patients with impaired hepatic functions and in elderly patients. Renal impairment does not affect the pharmacokinetics of felodipine, although accumulation of inactive metabolites occurs in renal failure. The bioavailability of felodipine is affected by the simultaneous ingestion of fatty food (increase in plasma level).