Amlodipine besilate is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile process of cardiac muscle and vascular smooth muscle dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine besilate inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. It acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
Atenolol is phenylacetamide, a selective β1 receptor blocker. It blocks the effects of adrenergic stimulation mediated through these receptors. The cardio-selectivity is dose related. Atenolol causes a reduction in blood pressure by lowering cardiac output, decreasing the plasma renin activity and sympathetic outflow from CNS. Atenolol also causes a reduction in myocardial oxygen demand by virtue of its negative inotropic and negative chronotropic effects.
Indications and Usage
- Angina pectoris
- Acute Myocardial Infarction
- Coronary heart disease
● Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance(afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
● The mechanism of action of Amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions.This dilation increases myocardial oxygen delivery in patients with coronary artery spasm. Atenolol is a beta-adrenoceptor blocking agent which is cardio-selective; its principal action is on beta-adrenergic receptors in the heart. It is without intrinsic sympathomimetic and membrane stabilising activities and as with other beta-blockers, has negative inotropic effects. It is probably assumed that the action of atenolol in reducing cardiac rate and contractility which makes it effective in eliminating or reducing the symptoms of patients with angina.
Amlodipine:Absorption: After oral administration, Amlodipine is well absorbed with peak plasma levels between 6-12 hours. Plasma levels peak 6-12 hr after oral administration; bioavailability is estimated to be 64-90%.
Distribution: Absolute bioavailability of the unchanged active substance is estimated to be 64-80%. Peak plasma levels are reached 6-12 hours after administration. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that amlodipine is bound to plasmatic proteins up to 97.5%.
Metabolism: About 90% converted to inactive metabolites hepatically.
Excretion: 10% of parent compound and 60% of the metabolites are removed in the urine; elimination from the plasma is biphasic with terminal half-life of about 30-50 hr.
Atenolol:Absorption: Absorption is rapid and with half life of 6-7 hr; about 50% of an oral dose is absorbed in the GI tract; plasma levels peak 2-4 hr after oral administration.
Distribution: only small amounts are reported to cross the blood-brain barrier and plasma-protein binding is minimal (approximately 6-16%). The plasma half-life is about 6-7 hours but this may rise in severe renal impairment since the kidney is the major route of elimination.
Metabolism: Atenolol undergoes little or no hepatic metabolism and more than 90% of that absorbed reaches systemic circulation unaltered.
Elimination: 50% of the oral dose is removed unchanged in the faeces; absorbed drug is removed mainly via renal elimination; half-life is about 6-7 hr.
Ampicillin at doses of 1 g and above may reduce atenolol levels.
Oral antidiabetics and insulin: β-blockers may decrease tissue sensitivity to insulin and inhibit insulin secretion e.g. in response to oral antidiabetics. Atenolol has less potential for these actions.
Ischaemic Heart disease: especially in patients with ischaemic heart disease, treatment should not be discontinued suddenly. The dosage should be gradually reduced, i.e. over 1-2 weeks, if necessary at the same time initiating replacement therapy, to prevent exacerbation of angina pectoris.
Lactation: The combination should not be used by nursing mothers. If its use is considered necessary, breast feeding should be stopped.