<unk>  is a long-acting calcium channel antagonist that selectively inhibits calcium ion influx across cell membranes. It targets L-type calcium channels in muscle cells and N-type calcium channels in the central nervous system which are involved in nociceptive signalling and pain perception.<unk>  has an inhibitory effect on calcium influx in smooth muscle cells to inhibit contraction.<unk>  ends up significantly reducing total vascular resistance without decreasing cardiac output expressed by pressure-rate product and cardiac contractability in comparison with verapamil, a non-dihydropyridine. In turn, following treatment lasting a month, with<unk> , cardiac output was significantly enhanced. Unlike verapamil which has efficacy in moderation of emotional arousal and reduces cardiac load without lowering cardiac output demands,<unk>  increases the cardiac output response concomitantly with increased functional cardiac load. Mechanism of action<unk>  is an angioselective calcium channel blocker and inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells which inhibits the contraction of cardiac muscle and vascular smooth muscle cells.<unk>  inhibits calcium ion influx across cell membranes, with a greater effect on vascular smooth muscle cells. This causes vasodilation and a reduction in peripheral vascular resistance, thus lowering blood pressure. Its effects on cardiac muscle also prevent excessive constriction in the coronary arteries. Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Among the two stereoisomers R(+), S(–), the (–) isomer has been reported to be more active than the (+) isomer. Serum calcium concentration is not affected by<unk> . And it specifically inhibits the currents of L-type Cav1.3 channels in the zona glomerulosa of the adrenal gland. The mechanisms by which<unk>  relieves angina are: * Stable angina:<unk>  reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, thereby lowering myocardial oxygen demand, at any given level of exercise. * Variant angina:<unk>  blocks spasm of the coronary arteries and restores blood flow in coronary arteries and arterioles in response to calcium, potassium, epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro.<unk>  has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid. Pharmacokinetics<unk>  and one of its major metabolites: The nitrogen-containing ring is oxidized, and two of the side chains are hydrolyzed.<unk>  has been studied in healthy volunteers following oral administration of 14C-labelled drug.<unk>  is well absorbed by the oral route with a mean oral bioavailability around 60%; the half-life of<unk>  is about 30 h to 50 h, and steady-state plasma concentrations are achieved after 7 to 8 days of daily dosing. In the blood it has high plasma protein binding of 97.5%. Its long half-life and high bioavailability are largely in part of its high pKa (8.6); it is ionized at physiological pH, and thus can strongly attract proteins. It is slowly metabolized in the liver by CYP3A4, with its amine group being oxidized and its side ester chain being hydrolyzed, resulting in an inactive pyridine metabolite. Renal elimination is the major route of excretion with about 60% of an administered dose recovered in urine, largely as inactive pyridine metabolites. However, renal impairment does not significantly influence<unk>  elimination. 20-25% of the drug is excreted in the faeces.
Amlodipine
Cyclothiazide
Chlorothiazide
Felodipine
Hydrochlorothiazide
Telmisartan
Spironolactone
Olmesartan