Nicardia-XL Mechanism of Action

Pharmacology: Pharmacodynamics: Nifedipine is a specific and potent calcium antagonist of the 1, 4-dihydropyridine type. Calcium antagonists reduce the transmembrane influx of calcium ions through the slow calcium channel into the cell. Nifedipine acts particularly on the cells of the myocardium and the smooth muscle cells of the coronary arteries and the peripheral resistance vessels. In hypertension, the main action of NICARDIA-XL-30 is to cause peripheral vasodilatation and thus reduce peripheral resistance. In angina, NICARDIA-XL-30 reduces peripheral and coronary vascular resistance, leading to an increase in coronary blood flow, cardiac output and stroke volume, whilst decreasing after-load. Additionally, nifedipine dilates submaximal both clear and atherosclerotic coronary arteries, thus protecting the heart against coronary artery spasm and improving perfusion to the ischaemic myocardium. Nifedipine reduces the frequency of painful attacks and the ischaemic ECG changes irrespective of the relative contribution from coronary artery spasm or atherosclerosis. NICARDIA-XL-30 administered twice-daily provides 24-hour control of raised blood pressure. NICARDIA-XL-30 causes reduction in blood pressure such that the percentage lowering is directly related to its initial level. In normotensive individuals, NICARDIA-XL-30 has little or no effect on blood pressure.
Pharmacokinetics: Absorption: After oral administration nifedipine is rapidly and almost completely absorbed. The systemic availability of orally administered nifedipine is 45 - 56 % owing to a first pass effect. Maximum plasma and serum concentrations are reached at 1.5 to 4.2 hours with NICARDIA-XL-30. Simultaneous food intake leads to delayed, but not reduced absorption.
Distribution: NICARDIA-XL-30 is about 95 % bound to plasma protein (albumin). The distribution half-life after intravenous administration was determined to be 5 to 6 minutes.
Biotransformation: After oral administration NICARDIA-XL-30 is metabolized in the gut wall and in the liver, primarily by oxidative processes. These metabolites show no pharmacodynamic activity. NICARDIA-XL-30 is excreted in the form of its metabolites predominantly via the kidneys and about 5 - 15 % via the bile in the faeces. The unchanged substance is recovered only in traces in the urine.
Elimination: The terminal elimination half-life is 6 - 11 hours, because of delayed absorption. In cases of impaired liver function the elimination half-life is distinctly prolonged and the total clearance is reduced. A dose reduction may be necessary in severe cases.