ANTIHISTAMINIC SUBSTANCES (synonym antihistaminic substances) — the antagonists of a histamine interfering its action on effector cells.
The most widespread And. treat the following chemical groups century: ethanolamines — Dimedrol (see), ethylene diamines — Suprastinum (see. Chloropyraminum ), fenotiazina — isopromethazine (see), tetragidrokarbolina — Diazolinum (see). They eliminate or reduce all effects histamine (see), except for its stimulating influence on secretion of a gastric juice. Antihistaminic substances prevent increase in a tone of smooth muscles of bronchial tubes, intestines, uterus, lowering of arterial pressure, increase in permeability of capillaries and edematization, a hyperemia and the itch arising at intradermal introduction of a histamine. And. block the receptive structures of fabrics sensitive to a histamine do not interfere with the release of a histamine arising at interaction of an antibody with antigen at damage of fabrics or administration of certain pharmacological substances century — so-called liberator of a histamine. And. have also antiallergenic activity century, edges it is expressed to a lesser extent, than antihistaminic action.
Many And. exert impact on c century. N of page.
Oppression of c is most characteristic. N of page, napr, at use of Dimedrol, derivatives of a fenotiazin and others And. century (sedative and somnolent effects). These substances are effective also at sea and aeroembolism, labyrinthites, vomiting of pregnant women (warn nausea, vomiting). Separate And. have anticonvulsant effect century.
Derivatives of a fenotiazin have property to strengthen effect of the narcotic, analgesic and anesthetizing substances, and also to lower body temperature. In high doses they usually cause excitement of c. N of page, followed motive and a hyperphrenia, the sleeplessness, a tremor raised by reflex irritability and other phenomena.
Some And. century (Teforinum) already in therapeutic doses exert exciting impact on c. N of page; Diazolinum does not cause the central effects.
And. exert a certain impact and on peripheral links of a reflex arc century. So, practically all And. have more or less expressed anesthetizing properties century; Dimedrol has ganglioblokiruyushchy effect, as a result to-rogo arterial pressure goes down. At the same time Diazolinum and derivatives of a fenotiazin in therapeutic doses do not oppress vegetative a ganglion. Isopromethazine, etizin and others And. century of a fenotiazinovy row block alpha adrenoreaktivnye structures. Many And. century also m - cholinolytic properties possess moderate spasmolytic.
And. are well soaked up both at parenteral, and at enteral introduction century. Duration of action of the majority And. century — 3 — 6 hours, isopromethazine — to 12 hours, Diazolinum — to 2 days.
And. apply hl century. obr. at various allergic states, especially at damage of skin and mucous membranes — a small tortoiseshell, a Quincke's disease, hay fever, allergic and vasculomotor rhinitis, allergic conjunctivitis, at the allergic states connected with reception of antibiotics or other medicines, etc. And. century sometimes use as hypnotic drugs (e.g., Dimedrol) and sedatives, it is rare — at parkinsonism, a chorea, vomiting pregnant, vestibular frustration.
Appoint And. century in, subcutaneously, intramusculary and intravenously. The drugs rendering irritant action (e.g., fenotiazina, Diazolinum), it is inside reasonable to appoint after food. To enter such And. century (especially derivative a fenotiazina) subcutaneously it is not recommended; at intramuscular injections there can be infiltrates.
And. century, as a rule, are well transferred by patients. The xerostomia is sometimes noted.
Dimedrol and fenotiazina is not recommended to be accepted in operating time to persons whose profession requires especially great attention and bystry reactions (workers of transport, etc.). It is reasonable to them to appoint And. century, not influencing c. N of page (e.g., Diazolinum).
At diseases of a liver and kidneys And. it is necessary to apply with care century.
During the work with isopromethazine it is necessary to observe precautionary measures since there can be an allergic damage of skin and mucous membranes.
From additional materials
ANTIHISTAMINIC SUBSTANCES, blockers of H 2 - receptors.
Blockers of H 2 - receptors exert the oppressing impact on histamine H 2 - receptors, to-rye participate in regulation of secretory activity of a stomach, a tone of unstriated muscles of a uterus, intestines and vessels, action of the heart, lipidic exchange. Receptors of this type are found also in c. N of page Besides, H 2 - receptors, apparently, play a part in development of allergic and immune processes since they are found on membranes of lymphocytes, mast cells, neutrophilic and basphilic leukocytes. The effects connected with excitement of histamine receptors of different localization are given in tab. 1.
Originally as a blocker of H 2 - receptors it was offered burimamid. However it was insufficiently active, possessed the expressed side effect and at introduction was inside inefficient. Then it was synthesized and investigated metiamid, to-ry differed from a burimamid in efficiency at introduction inside. Because ability of a metiamid to cause an agranulocytosis was found, its wedge, use was stopped. In modern medical practice as a blocker of H 2 - receptors Cimetidinum is used (a synonym Tagametum), to-ry has the expressed activity and has no serious side effect.
In the chemical relation blockers of H 2 - receptors it is possible to consider as derivatives of a histamine. The Imidazolny part of a molecule at them is kept and has the following structure:
The main modifications concern structure of a side chain (tab. 2).
Blockers of H 2 - receptors are competitive antagonists of a histamine concerning H 2 - receptors, the structure to-rykh is not established yet. It is possible that they or are closely connected with adenylatecyclase, or are one of its versions. It, e.g., is shown that at excitement by a histamine of H 2 - receptors of a mucous membrane of a stomach there is an increase in content of intracellular cyclic adenosinemonophosphate (tsAMF). The last is followed by increase in secretory activity of a stomach. Similarly inhibitors of phosphodiesterase — theophylline and caffeine work, to-rye also increase the maintenance of tsAMF and stimulate secretion of a stomach. Besides, increase in maintenance of tsAMF at stimulation by a histamine of H 2 - receptors it is established in mast cells, basophiles, T lymphocytes, cells of a myocardium, fatty tissue, nek-ry departments of c. N of page.
The most expressed effect of blockers of H 2 - receptors it is connected with their influence on secretion of glands of a mucous membrane of a stomach. They act on H 2 - receptors of covering cells also considerably reduce secretion salt to - you, edges raises under the influence of a histamine, Pentagastrinum, food, insulin, caffeine, and also at stretching of a stomach. Also basal secretion salt to - you decreases. The caused pepsinia and, perhaps, an internal factor of Kasl is to a lesser extent oppressed. The volume of a gastric juice decreases.
In experiments on animals it was shown that blockers of H 2 - receptors eliminate or reduce also other effects connected with excitement of histamine ^-receptors ((((((((((e.g., positive chronotropic effect, oppression of contractility of a myometrium, etc.). However practical importance of influence of blockers of H 2 - receptors on histamine receptors of different localization it is not found out yet.
Blockers of H 2 - receptors possess low lipofilyyustyo and therefore in c. N of page badly get. They are allocated preferential in not changed look, generally with kidneys (to 80 — 90%). Other part is removed through intestines where blockers of H 2 - receptors are allocated with bile. Blockers of H 2 - receptors apply at an ulcer of a duodenum and stomach, at a gipergastrinemiya, peptic (a reflux-) the esophagitis which is followed by the increased acid-forming function of a stomach. For this purpose use hl. obr. Cimetidinum. Appoint it inside and intravenously. Cimetidinum is usually well transferred. However at its use the gynecomastia, bradycardia, hypotension, a mialgiya, a diarrhea, a leukopenia, etc. are possible. At prolonged use of Cimetidinum it is necessary to control cellular composition of blood periodically.
Table 1. HISTAMINE RECEPTORS AND THEIR BLOCKERS
Table 2. CHEMICAL CONSTITUTION of the HISTAMINE AND BLOCKERS of N2-RETsEPTOROV
Bibliography: Mashkovsky M. D. Pharmaceuticals, p. 2, page 165, M., 1972; Barlow R. Century of Introduction to chemical pharmacology, L. — N.Y., 1964, bibliogr.; Pharmacological basis of therapeutics, ed. by L. S. Goodman a. A. Gilman, N. Y., 1970.; I. D ions. A new class of pharmacological drugs — blockers of histamine H 2 - receptors, Pharm, and toksikol., t. 51, No. 5, page 624, 1978, bibliogr.; Black J. W. and. lake of Definition and antagonism of histamine H 2 - receptors, Nature (Lond.), v. 236, p. 385, 1972; Hirschowitz B. I. H-2 histamine receptors, Ann. Rev. Pharmacol. Toxicol., v. 19, p. 203, 1979; Pearlman D. S. Antihistamines, pharmacology and clinical use, Drugs, v. 12, p. 258, 1976 bibliogr.; Third symposium on histamine H 2 - receptor antagonists, clinical results with cimetidine, Gastroenterology, v. 74, pt 2 p. 338, 1978.
D. A. Harkevich.