Sign Out
Cardiovascular therapeutic agent (antihypertensive and antianginal).
Pharmacology: Atenolol has an energy-sparing effect on the myocardium by avoiding the response to excessive β-adrenoreceptor stimulation which occurs during reflex tachycardia. This protection causes a reduced influx of Ca++ through the receptor-controlled Ca++-conducting channels. The result is an energy-sparing mechanism which makes more energy available in the form of adenosine triphosphate (ATP), so that structure and functions are maintained. The calcium antagonist, nifedipine also limit Ca++ influx but their mode of action differs from that of the β-blockers in that, they interact directly with the Ca++-conducting channels. In the myocardium, this causes energy preservation; in the vasculature, it results in coronary and peripheral vasodilatation. The antihypertensive effect of the calcium antagonists is readily explicable in forms of their direct inhibitor effect on Ca++ influx in response to membrane depolarisation. As for the β-blockers, there is as yet no satisfactory explanations for their blood pressure-lowering effect; although inhibition of a cyclic adenosine monophosphate (cAMP)-dependent smooth muscle contraction mechanism may be involved.
In marked contrast to the blood pressure-lowering effect of either verapamil or diltiazem (both of which have a direct inhibitory effect on atrionodal conduction), the blood pressure-lowering effect of nifedipine is accompanied by reflex tachycardia caused by excessive sympathetic drive. Since the β-blockers attenuate this reflex-induced tachycardia, and because the vasculature is highly sensitive to the calcium antagonistic activity of the dihydropyridine-based calcium antagonists, combined therapy of calcium antagonists (nifedipine) and β-blockers offers an advantage in the management of either hypertension or ischemic heart disease.
Another benefit to be obtained from the combination is in the management of cardiovascular disorders is that whereas some β-blockers alter the LDL/HDL cholesterol rates and so creates conditions which may favour atherosclerotic plaque formation, the calcium antagonists slow atherosclerosis. Also, the combined use of β-blockers and calcium antagonist is particularly advantageous in the management of ischemic heart disease because the calcium antagonists slow down ischemia-induced catecholamine release from the myocardium. In the presence of β-blockade, a raised level of catecholamines in the coronary circulation would promote coronary vasoconstriction, although the β-selective agents might ameliorate this effect to some extent.
Mechanism of Action: Nifedipine inhibits the influx of calcium into the heart muscle cells, smooth muscle cells of the coronary arteries and peripheral arterioles (resistance vessels). Nifedipine brings about an improvement in the oxygen supply to the heart muscle with simultaneous reduction of oxygen requirements, thereby exerting an antianginal effect. Normalisation of elevated blood pressure is brought about by a reduction of peripheral resistance through the dilation of the arterioles.
Pharmacokinetics: Mean peak plasma nifedipine level, following administration of capsule is 40.9 ng/mL. The Cmax of 45.7 ng/mL is observed at 5.3 hrs (Tmax) after administration of one Beta-Nicardia capsule. The T½ elimination for Beta-Nicardia capsule is 9 hrs.
