Central and peripheral anticholinergics (antispasmodics)

Excitation of muscular cholinergic receptors of myometrium causes an increase in hydrolysis of phosphoinositides, activation of phospholipase A ₂, activation of protein kinase C, reduction. The enhancement of the hydrolysis of phosphoinositides is selectively blocked by 4-DAPR, but not by pyrenesin and not by AF-DX116. The ability of muscarinic antagonists to reduce myometrium contractions caused by the agonist and data on the interaction of M-antagonists with M-cholinoreceptors of myometrium, obtained by functional studies and in binding experiments coincide. It is believed that it is difficult to consider that in the myometrium there are different subtypes of muscarinic cholinergic receptors. It is suggested that the muscarinic cholinergic receptors of the guinea pig myometrium belong to the M1 subtype. Muscarinic responses are more diverse in ionic mechanisms than nicotinic, Muscarinic cholinergic receptor, apparently, in all cases is associated with ion channels not directly, but through a system of biochemical reactions. There are 2 main ways - increased metabolism of phosphoinositides and inhibition of adenylate cyclase activity. Both these cascade reactions can lead to an increase in the intracellular Ca ²⁺ concentration required for many muscarinic responses. It is carried out by increasing the permeability of the membrane, which allows calcium ions to enter the cell from the environment, or through the release of Ca ²⁺ from intracellular stores.

The use of anticholinergics in genera, i.e., substances that block cholinoreactive biochemical structures by preferential central or peripheral action, seems promising. Due to the use of certain anticholinergics, the physician is able to selectively influence the transmission of cholinergic impulses in various parts of the brain or on the periphery - in the ganglia. If we take into account that cholinergic mechanisms participating in the regulation of the generic act are especially strongly toned during childbirth, then the danger of overexcitation of this highly sensitive system becomes evident. In-depth development by pharmacologists of the issues under consideration has shown that the central effect of some cholinolytics leads to a restriction of the flow of central impulses and, consequently, facilitates the normalization of relations between the higher centers of the nervous system and internal organs. This provides the latter with the necessary physiological rest and restoration of impaired functions.

Spazmolitin (tsifatsil, trazentin) refers to a group of central anticholinergic agents, as it has a pronounced effect on central cholinergic synapses. Central cholinolytics intensify the effect of neurotropic and analgesic agents, and, in contrast to M-cholinolytics, exert a facilitating influence on higher nervous activity in the form of intensification of excitatory and inhibitory processes, the ordering of higher nervous activity.

Spasmolitin has a relatively small atropyopodobnoy activity (j4) activity atropine). In therapeutic doses, it has no effect on pupil size, salivary secretion and heart rate. For midwifery practice, it is important that a large role in the antispasmodic effects of the drug is played by its miotropic action, expressed not worse than in papaverine. In this regard, spasmolitin is used in the clinic as a universal antispasmodic. Spasmolitin has a blocking effect on vegetative ganglia, adrenal medulla and hypophysialnal system.

It is believed that for clinical use the most promising are spasmolitin and aprofen. In contrast to M-holinolitikov, H-holinolitiki have fewer side effects (dilated pupils, dry mucous membranes, intoxication, drowsiness, etc.).

Spasmolitin at a dose of 100 mg inwards causes an improvement in conditioned reflex activity in humans, affecting the H-cholinergic structures of the subcortical formations, and also affect the increased motor activity, which is important in parturient women with a pronounced psychomotor agitation. Thus, pronounced motor excitation in childbirth is observed in 54.5% of cases.

Central cholinolytics, due to the blockade of cholinergic brain systems, primarily the reticular formation, as well as the cerebral cortex, prevent overexcitement and depletion of the central nervous system and thereby prevent shock states.

Dosage of spasmolytic during pregnancy and childbirth: a single single dose of 100 mg orally; the total dose of spasmolitin during delivery is 400 mg. Side effects and contraindications for the use of spasmolytic in pregnant women and parturient women have not been noted.

Aprofen. The drug has peripheral and central M- and H-cholinolytic action. The peripheral holi-nolytic effect is more active than spasmolytic. Has also an antispasmodic effect. Causes increased tone and increased uterine contractions.

In obstetric and gynecological practice, they are used to stimulate labor: along with increased uterine contractions, aprofen reduces spasms of the pharynx and promotes more rapid opening of the cervix in the first stage of labor.

Assign inside after eating at a dose of 0.025 g 2-4 times a day; under the skin or intramuscularly injected 0.5-1 ml of a 1% solution.

Metacin. The drug is a very active M-cholinolytic agent. It is a selectively acting peripheral anticholinergic. On the peripheral cholinergic receptors, methacin acts more strongly than atropine and spasmolytic. Metacin is used as a cholinolytic and antispasmodic agent for diseases accompanied by spasms of smooth muscle organs. Metacin can be used to relieve the increased excitability of the uterus in the event of the threat of premature birth and late miscarriages, for premedication in the operation of cesarean section. The use of the drug reduces the amplitude, duration and frequency of uterine contractions.

Metacin is prescribed inside before meals to 0,002-0,005 (2-5 mg) 2-3 times a day. Under the skin, in the muscles and in the vein, inject 0.5-2 ml of a 1% solution.

Halidor (benzciclane) is a drug many times greater than the effectiveness of papaverine for peripheral, spasmolytic and vasodilating effect. In addition, the drug has a tranquilizing and local anesthetic effect. Halidor - the compound is low-toxic and causes only minor side effects.

It has been proved that halide is less toxic than papaverine in all modes of administration. Teratogenic effect was studied on a large number of animals - mice, rabbits, rats (100-300). According to the studies, when a halide was administered at 10-50-100 mg / kg rats and mice and 5-10 mg / kg - rabbits were not detected from the very beginning of pregnancy, despite extremely high doses.

Galidor has a pronounced direct myotropic action: at a concentration 2-6 times lower than papaverine, it relieves spasmodic contractions of the myometrium caused by oxytacin. The drug also has a clear local anesthetic effect.

When studying the effect of halide on blood circulation in an experiment on anesthetized cats and dogs, intravenous administration at a dose of 1-10 mg / kg of body weight caused a temporary decrease in blood pressure, but less and less than papaverine. The drug increases the coronary circulation and reduces the resistance of the coronary arteries, as well as intracarotide administration of the drug causes a significant, but short-term increase in the blood supply to the brain (in an experiment on cats).

By strength and duration of action on cerebral circulation, the halideor excels no-shpa and papaverine, without creating a disproportion between the blood supply to the brain and the consumption of oxygen by the brain tissue.

In clinical conditions, a significant peripheral vasodilator effect of the halidor was revealed. The drug is also used to remove peripheral spasms in anesthesia and surgery. Halidor is widely used in the treatment of disorders of coronary circulation, since it sharply increases oxygen utilization by myocardium and shifts the ratio of the concentration of oxidized and reduced forms toward accumulation in the myocardium of the latter.

Recently, new data on the effect of a halidor on the heart have been obtained. Its "classical", expanding coronary vessels effect is favorable for various forms of anginal pain, since the drug is not too strong a vasodilator - it has antiserotonin effect. The vagolytic effect on the heart, as well as the specific inhibition of certain metabolic processes, acting on the metabolism of the heart, has been revealed.

For obstetric practice, visceral spasmolytic action of the halidor is most typical. Ceasement of dysmenorrhoeic pain was noted. Due to its tranquilizing effect, the drug reduces mental stress in the premenstrual period. In the experiment, some authors developed an in vivo technique for assessing the spasmolytic activity of drugs in rats by measuring contractions of smooth muscles in response to topical application of acetylcholine. The proposed scheme for setting up the experiment makes it possible to quickly assess the potential selectivity of the action of antispasmodics on individual internal organs - the relative activity of antispasmodics with respect to suppression of contractions of the hollow organ (uterus, bladder, colon and rectum) caused by topical application of acetylcholine is determined.

Galidor is successfully appointed in the period of the disclosure of the cervix and the expulsion of the fetus. In cases of spastic ejection of the uterus under the influence of the drug, the duration of I and II birth periods decreases. In studies, the spasmolytic effect of halidor was studied in coordinated labor, dystocia of the cervix. The shortening of the opening period and the smoother movement of the head along the generic paths were noted.

In comparison with no-shpa and papaverine, the halide has a more pronounced antispasmodic effect in the absence of changes in the pulse rate and blood pressure. The drug is well tolerated by women giving birth at a dose of 50-100 mg inside, intramuscularly and intravenously in a mixture with 20 ml of 40% glucose solution.

Absolute contraindications to the use of a halidor. Side effects are extremely rare and harmless. There are reports of nausea, dizziness, headache, dry mouth, throat, drowsiness, as well as allergic skin rashes.

When parenteral administration of the drug in extremely rare cases, there are local reactions.

Form release: tablets (pills) to 0.1 g (100 mg); 2.5% solution in ampoules of 2 ml (0.05 g or 50 mg of the drug).

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]