ADRENOMIMETICHESKY MEANS (Latin adrenalis — the epinephral and Greek mimztikos — imitating, reproducing) — the chemical compounds operating like adrenaline. These means call also simpatompmetpcheskpm since under their influence in an organism there are phenomena similar to effects of excitement of sympathetic nerves.
In medical practice derivatives of fenilalkilamin which molecule consists of the phenolic kernel connected by an aliphatic chain to an amino group (tab.) are used.
Pharmacological properties and activity of Ampere-second. it is possible to change by joining of hydroxylic radicals to an aromatic ring, aliphatic group and methyl radicals to an amino group, and also increase in number of carbon atoms in an aliphatic chain.
Ampere-second. divide into two groups: 1) Ampere-second. direct action — adrenaline (see), noradrenaline (see), a phenylephine hydrochloride (see), Phethanolum (see), Isadrinum (see), etc.; 2) Ampere-second. indirect action — ephedrine (see), Phenaminum (see), Naphthyzinum (see), tyramine, etc. Some fenilalkilamina of direct action (adrenaline, noradrenaline, Isadrinum) in physiological conditions are the adrenergic mediators relating to group of pyrocatechins or catecholamines. The mechanism of effect of drugs of this group comes down to the excitement of a postsynaptic membrane of an adrenergic synapse resulting from their direct interaction with adrenoreaktivny systems (see).
According to the standard division of adrenoceptors on α-and β-adrenoceptors of Ampere-second. divide into α-adrenomimetik (noradrenaline, a phenylephine hydrochloride, Phethanolum) and β-adrenomimetik (Isadrinum). Adrenaline interacts both with α-, and with β-adrenoceptors.......... This division is conditional since means only preferential influence of funds for the corresponding type of an adrenoceptor caused to some extent by features of a structure of Ampere-second. The greatest α-адреномиметической activity the connections having the replaced NH2 group, napr, noradrenaline possess. Replacement of hydrogen atom of an amino group with one methyl group weakens α-adrenomimetichesky properties (phenylephine hydrochloride) and promotes manifestation of β-adrenomimetichesky activity (adrenaline). During the replacement of hydrogen atom of an amino group with a branched carbon chain (isopro-saw) connection gains strongly expressed β-adrenomimetpchesky activity (Isadrinum).
Proceeding from modern ideas of a structure of adrenoceptors, it is possible to consider that the active complex of adrenomimetik with α-adrenoreaktivny system is formed owing to accession to it of a small cationic head of substance (adrenaline, noradrenaline). Increase in a cationic head of an adrenomimetik by substitution of hydrogen interferes (Isadrinum) with formation of strong communication with a α-adrenoceptor and leads to strengthening of β-adrenomimetichesky properties. It is supposed that the pirokatekhinovy (katekholovy) kernel plays a major role in excitement of β-adrenoceptors [[[[[[[[[[Bello (V. Belleau), 1963].
Ampere-second. indirect action exert impact to hl. obr. on presinaptpchesky structures of adrenergic fibers, strengthening allocation in them natural mediators — noradrenaline and adrenaline. Adrenomimetpchesky effect of these drugs is caused also by their property to reduce deposition of adrenaline and noradrenaline and to oppress active return capture of these mediators presynaptic nerves of adrenergic nerves. Adrenomimetichesky effects of ephedrine, perhaps, are connected partially and with its antimonaminoksidazny activity. Methylation of β-carbon atom of an aliphatic chain causes exciting influence of ephedrine and especially Phenaminum on c. N of page. All Ampere-second. (except for Isadrinum) have pressor and vasoconstrictive effect at topical administration. On pressor activity of Ampere-second. it is possible to arrange in the following order: noradrenaline, adrenaline, phenylephine hydrochloride, Phethanolum, ephedrine, Naphthyzinum. In pressor action of the majority of Ampere-second. allocate several phases. which are especially accurately expressed at adrenaline, noradrenaline, it is less — at a phenylephine hydrochloride and Phethanolum and and are practically not allocated at ephedrine and Naphthyzinum. The first phase — sharp increase in arterial pressure, a cut at administration of adrenaline is caused by strengthening of cordial activity, and at introduction of noradrenaline — sharp vasoconstriction. The second phase — reduction of rise or even lowering of arterial pressure. This phase is short and is a consequence of reflex activation of the item vagus. The vagal phase is not always found at introduction of a phenylephine hydrochloride and Phethanolum and is not characteristic of pressor effect of ephedrine at all. The third phase — the well-marked and long increase in arterial pressure caused by sharp vasoconstriction of an abdominal cavity and skin in which α-adrenoceptors are put preferential.......... In pressor effect of adrenaline allocate also the fourth — the depressor phase caused by vasodilatation of lungs, skeletal muscles, kidneys, a brain under the influence of excitement of the β-adrenoceptors put in them.......... The depressor effect of adrenaline without the previous increase in arterial pressure can be gained against the background of action of α-adrenolytic means (see. Adrenolytic means).
Duration of pressor action of Ampere-second. depends on speed of their inactivation. The longest increase in blood pressure causes ephedrine, then Phethanolum, a phenylephine hydrochloride, noradrenaline and adrenaline. Short duration of effect of adrenaline and noradrenaline is explained by their bystry inactivation. The entered adrenaline collapses under the influence of catechol-O-methyltransferase (KOMT) and turns in metanefrin (apprx. 70%), is inactivated by oxidizing deamination at monaminoksidaza (MAO) — about 20 — 25% — or by hpnopdny oxidation helped, an end product to-rogo is adrenokhry (see the scheme on p. 114).
Ampere-second., only one hydroxylic radical (a phenylephine hydrochloride, Phethanolum) containing in the molecule or not having these radicals (ephedrine) at all have more long effect in comparison with other dioxyderivatives (adrenaline, noradrenaline, Isadrinum) since KOMT slowly collapse and are exposed to quinoid oxidation less. Besides, ephedrine thanks to presence of the metalny radical at one of carbon atoms in an aliphatic chain does not give in to influence of MAO.
Practically all Ampere-second. exert the stimulating impact on heart. Along with increase of cordial reductions and increase in their intensity under the influence of adrenomimetik the need of a cardiac muscle for oxygen sharply increases, carbohydrate and electrolytic metabolism in a myocardium is broken and conditions for developing of arrhythmia are created. Adrenaline has the most expressed cardiotonic and aritmogenny effect.
Ampere-second. differently change a tone of smooth muscle bodies that depends on preferential influence of funds for this or that type of adrenoceptors and on physiological function of the excited adrenoceptor. So, β-адреномиметик Isadrinum, α-and β-адреномиметик adrenaline and adrenomimetik indirect action ephedrine cause a bronchiectasia. Isadrinum has the strongest bronchodilatory effect. α-Adrenomimetiki (noradrenaline, a phenylephine hydrochloride and Phethanolum) do not cause bronchodilatory effect. As β-, and α-adrenomimetik (adrenaline, Isadrinum, ephedrine, noradrenaline) brake a peristaltics of a stomach and intestines. Under the influence of Ampere-second., exciting α-adrenoceptors, there is a reduction of muscles of sphincters went. - kish. path. Ampere-second. cause also a mydriasis, reduction of a spleen and pilomotor muscles. Under the influence of Ampere-second. content in blood of glucose, fatty acids (adrenaline, noradrenaline) increases, the c is excited. N of page (ephedrine, Phenaminum).
Most often Ampere-second. apply as the means increasing arterial pressure. For this purpose they are appointed at the acute lowering of arterial pressure (collapse) arising owing to surgical interventions, injuries, poisonings, blood losses (noradrenaline, adrenaline, a phenylephine hydrochloride, Phethanolum, ephedrine). At the same time it is necessary to remember that adrenaline causes a depressor effect therefore in this case it is better to use noradrenaline, a phenylephine hydrochloride, Phethanolum of a pla to apply adrenaline in a combination with a phenylephine hydrochloride or ephedrine. Besides, at intravenous administration of adrenaline there can be arrhythmias. Ephedrine as it is longest acting, though less active in comparison with other adrenomimetika, drug is used for the prevention of repeated falloff of arterial pressure. The phenylephine hydrochloride, Phethanolum, ephedrine apply also at lowering of arterial pressure, a cut the nek-eye accompanies infectious diseases, at neurocirculatory and vegeto-vascular dystonias.
Ampere-second. (adrenaline, a phenylephine hydrochloride, Phethanolum) add to solutions of some anesthetics that leads to prolongation of their action and reduction of bleedings. The phenylephine hydrochloride and ephedrine apply also at spinal anesthesia for the purpose of prevention of a lowering of arterial pressure.
Topical administration of drugs (wetting of tampons) is shown for a stop of bleedings and reduction of the inflammatory phenomena at acute and chronic rhinitises, sinusitis, laryngitis, conjunctivitis. For this purpose most often use adrenomimetichesky means of indirect action — ephedrine of N Naphthyzinum. However it is necessary to consider that at prolonged use of these drugs there is an easing of effect owing to the tachyphylaxis (see) resulting from exhaustion of reserve fraction of mediators in presynaptic nerves. Therefore in 5 — 7 days of use of drugs it is necessary to take a break.
Ampere-second. widely apply to treatment of bronchial asthma (adrenaline, Isadrinum, ephedrine), to stopping of heavy long attacks of a bronchospasm and not heavy attacks of bronchial asthma. Sometimes Ampere-second. use at treatment of allergic diseases (hay fever, a small tortoiseshell), myasthenias (ephedrine), at the hypoglycemic coma caused by overdose of insulin (adrenaline).
Ampere-second. at prolonged use or overdose cause by-effects: permanent increase in arterial pressure, the increase of heartbeat which is replaced by bradycardia, arrhythmias most of which often arise at use of adrenaline and noradrenaline. Prolonged use of ephedrine can cause nervous excitement, sleeplessness.
At intravenous administration of high doses of adrenaline, noradrenaline and phenylephine hydrochloride there can be acute poisoning. At the same time strong heartbeat, an asthma, a vasospasm of a big circle of blood circulation, arrhythmia, appears in hard cases trembling of a myocardium, a fluid lungs, hematencephalons. At acute poisoning with ephedrine along with the specified phenomena the hyperphrenia, motive concern, a tremor of extremities, sweating, rash is noted. Treatment of poisonings: rest, inhalation of an amilnitrnt, nitroglycerine of 1 — 2 drop under language, vasodilating drugs (a papaverine, aminazine, an Euphyllinum), 10 — 20 ml of 40% of solution of glucose in a vein, bloodletting, an artificial respiration; at a fluid lungs — cordial glnkozida (strophanthin); at acute poisoning with ephedrine barbiturates are shown. Hron. poisoning of Ampere-second. (according to an experiment) is followed by degenerative changes of walls of vessels and a myocardium.
Ampere-second. are contraindicated at a hypertension, the expressed atherosclerosis, tendency to vasospasms, heavy organic heart diseases, a gnpertireoza, diabetes, pregnancy. Introduction of noradrenaline and adrenaline contraindicated at a ftorotanovy, cyclopropane and chloroformic anesthesia. To the people of advanced age and patients having sleeplessness, Ampere-second. it is necessary to appoint with care.
Bibliography: Biogenic amines in clinic, under the editorship of V. V. Menshikov, M., 1970; Matlin E. Sh. and Menshikov V. V. Clinical biochemistry of catecholamines, M., 1967; Mashkovsky M. D. Pharmaceuticals, p.1, M., 1972; Ahlquist R. P. Adrenergic drugs, in book rPharmacol. in Med., ed. by V. A. Drill, p. 378, N. Y. a. o., 1958; Belleau B. An analysis of drug-receptor interactions, Proc. first int. pliarmacol. meeting, v. 7, p. 75, Oxford a. o., 1963, bibliogr.; Ehrenpreis S., Fleisch J. H. a. Mittag T. W. Approaches to the molecular nature of pharmacological receptors, Pharmacol. Rev., v. 21, p. 131, 1969, bibliogr.; Pharmacological basis of therapeutics, ed. by L. S. Goodman a. A. Oilman, N. Y., 1970.
Yu. D. Ignatov.