OCTADINUM (Octadinum; synonym: Guanethidini sulfas, Ipoctal, Ismelin, Izobarin, Octatensine, Sanoten. sin etc.; joint venture. B) — sympatholytic. beta (N-Azotsiklooktil) - ethylguanidine sulfate; With 10 H 22 N 4 • 0,5H 2 SO 4 :
White crystal powder of bitter taste, slightly soluble in water.
Blocks transfer of nervous impulses from sympathetic nerves on executive bodies, making selective impact on bombways of axons of adrenergic neurons. A basis of the mechanism of sympatholytic action of O. is its ability to interfere with return of noradrenaline from a synaptic gap in an axon and to reduce stocks labilno of the mediator connected in them. Getting in adrenergic axons, O. collects in granules and forces out from them noradrenaline, to-ry partially collapses axonal MAO. Not collapsed part of noradrenaline comes to a synaptic gap, causing a sympathomimetic phase of action of O. Istoshcheniye of stocks of noradrenaline in adrenergic axons leads to the termination of function of sympathetic nerves. For the same reason O. eliminates effects of sympathomimetics of indirect action (tyramine, ephedrine). Effects of noradrenaline and adrenaline at prolonged use of O., on the contrary, amplify in connection with arising (owing to sympathetic denervation) hypersensitivity of adrenoceptors of executive bodies to them.
In operation O. clearly are allocated for functions of cardiovascular system three phases. Originally O. causes a nek-swarm increase in the ABP that is caused by hl. obr. the arising tachycardia and increase in cordial emission. Duration of this sympathomimetic phase of action fluctuates from one to several hours. Further progressive decrease in the system, diastolic and systolic ABP is observed, the heart rate, minute volume and pulse pressure decreases. Hypotensive action of O. is caused by decrease in sympathetic influences on heart and vessels owing to what vascular resistance to a blood flow falls, the venous pressure and venous return decreases, cordial emission considerably decreases. Reduction of the last is followed by pressure decline in system of a small circle of blood circulation, speed of a blood-groove in system hepatic and renal arteries, temporary reduction of filtrational function of kidneys. Persistent hypotension after oral administration of O. develops on 2 — 3 days and remains during 2 — 4 weeks. At prolonged use of O. its hypotensive action is weakened since cordial emission is normalized (hl. obr. as a result of a delay of sodium and water in an organism and increases in volume of the circulating blood). Also developing sensitization of muscles of vessels and hearts to influence of endogenous catecholamines matters.
Affecting a sympathetic innervation of an eye, O. causes narrowing of a pupil, strengthening of outflow of watery moisture, reduction of its education that leads to decrease in intraocular pressure.
O.'s absorption from went. - kish. a path varies and usually makes apprx. 30% of the drug administered inside. The main part of the soaked-up O. is removed by kidneys in not changed look. Residual quantities it are found in urine within 10 — 14 days. O.'s metabolism is carried out preferential in a liver with participation of its microsomal enzymes.
Lake. apply in quality antihypertensive (see) for treatment of an idiopathic hypertensia (especially in the III stage). It is preferable to carry out treatment in the conditions of a hospital. Besides, O. apply in eye practice to treatment of primary wide-angle glaucoma.
As antihypertensive of the Lake. appoint inside. Initial doses of drug shall not exceed 0,01 — 0,0125 g once a day. In the subsequent the dose is raised on 0,01 g through everyone 3 — days to 0,05 — 0,075 g a day, it is rare — to 0,1 g. To persons of senile age appoint no more than 0,05 g a day. The daily dose is divided on 1 — 3 reception.
In eye practice of O. apply in the form of 5% of solution, appointing it on 1 — 2 drops for instillation in a conjunctival sac of 1 — 2 time a day.
Side effect The lake is shown most often by nausea, dizzinesses, and also swelling of a mucous membrane of a nose, a cut is stopped by instillation of solution Naphthyzinum (see). Sometimes O. causes abdominal pains and ponosa because of strengthening of a vermicular movement of intestines that is result of elimination under the influence of drug of sympathetic braking of motor function of intestines. In case of ponos it is necessary to appoint holinoblokator, napr, atropine (see), Methacinum (see), etc. At prolonged use of O. strengthening of a reabsorption of ions of sodium in tubules of kidneys and a delay of sodium salts and water in an organism is observed that reduces efficiency of drug as antihypertensive. It is reasonable to apply to correction of these disturbances along with O. dichlothiazide (see). During the maximum hypotensive action of O. (on 5 — the 10th day) development of an orthostatic collapse is possible, for the prevention to-rogo a daily dose of O. it is necessary to increase gradually. Besides, the patient recommend not to accept vertical position earlier, than in 2 — 3 hours after administration of drug. The island is contraindicated at acute disorders of blood circulation of a brain, heart, at insufficiency of secretory function of kidneys, acute glaucoma. It is irrational to lake to appoint together with antidepressants.
Form of release: tablets on 0,025 g. Keep in the dry, protected from light place.
See also Sympatholytics .
Bibliography: Having bitten all over V. V., etc. Clinical pharmacology, page 93, M., 1978; Komissarov I. V. Medicinal regulation of adrenergic processes, page 71, Kiev, 1976; In about u of an A. L. a. Green A. F. Adrenergic neurone blocking agents, Ann. Rev. Pharmacol., v. 5, p. 183, 1965; The pharmacological basis of therapeutics, ed. by L. S. Goodman a. A. Gilman, N. Y., 1975; S a n n e r-stedt R. Conway J. Hemodynamic and vascular responses to antihypertensive treatment with adrenergic blocking agents, Amer. Heart J., v. 79, p. 122, 1970.
I. V. Komissarov.