CIBA-GEIGY Pharmaceuticals [antikvár]

-7- ADELPHANE Antihypertensive COMPOSITION 3,4,5-Trimethoxybenzoyl-methyl-reserpate (=reserpine.). Reserpine is a pure Rauwolfia alkaloid. 1,4-Dihydrazinophthalazine sulphate (=dihydralazln.sultat.). Dihydralazine is a phthalazine derivative. Tablets containing 0.1 mg reserpine and 10 mg dihydralazine sulphate; PROPERTIES Adelphane contains two components which have differing sites of attack and whose blood pressure lowering effects are mutually complementary. Reserpine Reserpine depletes the catecholamine depots in the post-ganglionic sympathetic nerve endings and in the central nervous system, this depletion being followed by a relatively prolonged inability to store catecholamines. As a result, sympathetic tone diminishes, whereas the activity of the parasympathetic nervous system remains unaffected. Elevated blood pressure is thus lowered, while at the same time the heart rate decreases and a sedative influence is exerted on the central nervous system. As a rule, the maximum response is attained only after 2-3 weeks. Dihydralazine By acting directly upon muscle tissue in the blood vessels - primarily in the arterioles -dihydralazine induces peripheral vasodilatation, thereby lowering elevated blood pressure. Characteristic of dihydralazine is the fact that it also reduces vascular resistance In the brain and in the kidneys. Renal blood flow is satisfactorily maintained during long-term treatment. Dihydralazine lowers blood pressure in both the standing and the lying position without provoking any marked symptoms of postural hypotension. PHARMACOKINETICS Reserpine Reserpine Is rapidly absorbed by the oral route, its bioavailability amounting to approx. 50%. Measurable concentrations already appear In the plasma after 30 minutes. The plasma protein-binding rate for reserpine is 96%. After an oral dose, metabolism or reserpine sets in rapidly. Reserpine and its metabolites show a bipha-sic pattern of elimination from the plasma, the respective halt-lives being 4.5 hours and 271 hours. Within the first 96 hours after oral administration, 8% of the dose is excreted In the urine (mainly in the form of metabolites) and 62% in the faeces (mainly In the form of reserpine). Reserpine crosses the placental barrier and also passes into the breast milk. In the presence of renal failure, the slower urinary excretion of reserpine is offset by excretion on a larger scale in the faeces, so that no accumulation occurs. Dihydralazine Dihydralazine is rapidly absorbed by the oral route. Its elimination half-lite averages 4-5 hours, approx. 10-15% of the dihydralazine in the plasma becomes metabolised to hydralazine. Studies to date indicate that actylator status plays no clinically relevant role In connection with dihydralazine. It Is not yet known whether dihydralazine undergoes acetylation during Its metabolism. INDICATION Hypertension. DOSAGE The dosage of Adelphane should be individualised. Treatment Is initiated with doses as low as possible, which - depending on the patients response - may slowly be raised; one should not exceed a daily dosage of 5 tablets (0.5 mg reserpine, 50 mg dihydralazine). The daily dosage should be taken In 2-3 single doses. For maintenance therapy, the lowest dosage that still proves adequate should be employed. On