PROPRANOLOL (Propranololi Hydrochloridum; synonym: anaprilin, inderal, Obsidanum, Stobetinum, Alindol, Betadren, Deralin, Kemi, Noloten, Propanim, Propranolol Hydrochloride) — a beta adrenceptor blocking agent. 1-Izopropilamino-3-(1-naftoks) - 2 propyl alcohols a hydrochloride; With 16 H 21 NO 2 • HCl:
Powder of bitter taste, white or white with slightly pinkish shade, inodorous. Let's dissolve in water, alcohol, we will badly dissolve in chloroform, it is almost insoluble on air, is not stable on light. Pier. weight (weight) 295,8.
The item is beta adrenoblocker of not selective effect, has internal sympathomimetic (partial agonistic) no activity and has membrane stabilizing effect. Like other beta adrenoblockers causes reduction of force and frequency of reductions of heart, cordial emission, consumption by a myocardium of oxygen, speed of carrying out excitement on the carrying-out system of heart, suppresses ectopic activity of auricles and ventricles, and also weakens reactions of heart to a stress and loading. Besides, P. slows down lipolytic and glikogenolitichesky action of catecholamines. The main therapeutic effects of P. (hypotensive, anti-anginal and antiarrhytmic) are directly or indirectly caused by elimination of adrenergic influences on heart. The mechanism of hypotensive action of P. is connected with reduction of cordial emission, activity a renin-angiotenzinnoy of system, decrease in sensitivity of a barorecrptor reflex, adaptation decrease in a tone of arteries in response to decrease in pumping function of heart (via the mechanism of a system autoregulyation) and, at last, with blockade of the central beta adrenoceptors. The mechanism of anti-anginal effect of P. is explained, on the one hand, with reduction of consumption by a myocardium of oxygen due to decrease in a metabolic cost of heart and, on the other hand — redistribution of a regional coronary blood-groove of a myocardium in favor of the ischemic centers (generally subendocardial which blood supply at ischemia of a myocardium suffers more than subepicardial layers). As a result of it the main pathogenetic mechanism of stenocardia — disturbance of compliance between delivery of oxygen and consumption by his ischemic myocardium is eliminated. The mechanism of antiarrhytmic action of P. is caused by elimination of aritmogenny sympathetic influences on the carrying-out system of heart by braking of heterogeneous automatism and rate of propagation of excitement through an atrioventricular node, increase in the refractory period.
At intake of P. it is soaked up almost completely (90% of the accepted dose), the maximum concentration in blood is created in 1 — 2 hour. The item collects in lungs, a brain, a liver, kidneys and heart.
To 85 — 96% circulating in blood P. contacts proteins of plasma. The main ways of biotransformation of P. in a liver are O-dealkylation, oxidation of a side chain and naphthalenic ring, Konjyugirovaniye with glucuronic to - that. One of the main metabolites of P. (4-oksipropranonol) does not concede P. on beta and adrenoceptor blocking activity. P.'s metabolites are allocated to hl. obr. with urine.
Items apply to treatment of an idiopathic hypertensia easy and moderate severity, an angina of exertion and supraventricular arrhythmias. There are data on P.'s efficiency at a hyperthyroidism, alarming states, a hypertrophic subaortal stenosis, Fallo's tetrad, kauzalgiya, glaucoma, migraine and a pheochromocytoma.
Appoint inside or parenterally. Doses select individually according to reaction of the patient to drug. Inside appoint 0,01 — 0,04 g 3 — 4 times a day after food in the beginning. If necessary the daily dose can be increased to 0,4 g and more. Drug is accepted courses on 3 — 4 weeks with breaks in 1 — 2 month. In some cases (e.g., at arrhythmias) P. is appointed constantly for a long time. For bystry stopping of cardiac arrhythmias of P. enter intravenously (slowly) on 1 ml 0,1% of solution. If necessary the drug in the same dose is administered repeatedly with intervals 2 min. before emergence of effect. Total quantity of 0,1% of solution shall not exceed 10 ml. The patient who is under anesthetic enter no more than 5 ml of 0,1% of solution.
Side effect of P. is shown by hl. obr. reactions from outside went. - kish. a path (nausea, vomiting, diarrhea or locks) and cardiovascular system (the expressed to bradycardia, heart failure, hypotension, a heart block, Reynaud's phenomenon). Development of a depression, hallucinations, sleep disorders and sight, a bronchospasm is sometimes possible. Besides, P. can cause an alopecia, an erythema, psoriazopodobny rash and disturbances of a hemopoiesis (an agranulocytosis, a Werlhof's disease). At development against the background of P.'s action of symptoms of heart failure appoint cardiac glycosides. The item is incompatible with inhalation anesthetics (danger of oppression of contractility of heart), MAO inhibitors and hypoglycemic substances (danger of a hypoglycemia). The item is contraindicated at bronchial asthma and hron. obstructive diseases of lungs, the sinus bradycardia and the progressing heart block, cardiogenic shock expressed to right ventricular insufficiency and congestive heart failure.
Forms of release: tablets on 0,01 or 0,04 g; ampoules on 1 and 5 ml of 0,1% of solution. Storage: in the place protected from light.
See also Adrenolytic means .
Bibliography: Beta-adrenoceptor blocking agents, ed. by P. R. Saxena a. R. P. Forsyth, Amsterdam — Oxford, 1976; Me Devitt D. G. Adrenoceptor blocking drugs, clinical pharmacology and therapeutic use, Drugs, v. 17, p. 267, 1979.
S. D. Yuzhakov.