ANTI-INFLAMMATORY DRUGS — the pharmaceuticals suppressing manifestations of inflammatory processes.
Many pharmaceuticals relating to different groups pharmacological of active connections have antiinflammatory activity. However vast majority of scientists carry to P. page only those medicinal substances which suppress manifestations inflammations (see) due to influence on various mechanisms of a pathogeny of inflammatory processes, i.e. acting by the pathogenetic principle. The antiinflammatory effect of such P. of page is shown irrespective of the nature and character of the causative factors causing emergence of inflammatory reactions.
At inflammatory processes inf. origins antiinflammatory effect render antibiotics and other chemotherapeutic means. Antiinflammatory action of these means is caused generally by suppression of life activity of microorganisms and is shown preferential concerning the inflammatory processes caused by microflora. Thus, unlike P. antibiotics and other chemotherapeutic means affect with page septic forms of an inflammation by the etiotropic principle. Separate chemotherapeutic means (e.g., streptocides, tetracyclines, etc.) can exert also a nek-swarm the oppressing impact and on processes of an aseptic inflammation. However such properties at chemotherapeutic means are expressed very poorly and have no essential value in the mechanism of their antiinflammatory action. In this regard chemotherapeutic drugs usually are not considered as P. by page.
On a chemical structure pathogenetic the pages operating with P. divide on steroid and nonsteroid.
To steroid Items of page carry glucocorticoids (see. Glucocorticoid hormones ), among which distinguish the drugs used for resorptive and local action — hydrocortisone (see), Prednisonum (see), Prednisolonum (see), dexamethasone (see), Triamcinolonum (see), etc., and also the drugs intended only for topical administration — a flyuotsinolon acetonide, a flyumetazon pivalat, betamethasone, etc. At steroid P. antiinflammatory properties are combined by page with an immunodepressive effect.
To nonsteroid Items of page belong derivatives of some carboxylic to - t, pyrazyl ketone and an oksikam. Almost important P. of page from derivatives carboxylic to - t are salicylates — acetylsalicylic acid (see), sodium salicylate (see), Salicylamidum (see); derivatives indolacetic to - you — indometacin (see), sulindak; derivatives alpha-toluic to - you are diclofenac-sodium (Voltarenum) and fenklofenak; derivatives fenilpropionovy to - you are an ibuprofen, Naproxenum, etc.; derivatives anthranilic (fenamovy) to - you — mefenamovy to - that, flyufenamovy to - that, etc. From derivatives of pyrazyl ketone as nonsteroid P. villages use pyramidon (see), analginum (see), Butadionum (see), oxyphenylbutazone, etc., and from derivatives of an oksikam — piroxicam. At all listed above nonsteroid P. antiinflammatory properties are combined by page with analgesic and febrifugal action. As P. villages use also knitting and enveloping means (see), and also drugs of a row medicinal plants (see), napr, a yarrow, a sage, etc. which have local antiinflammatory action at some diseases of skin and mucous membranes.
Also the substances belonging to other classes of nonsteroid connections, napr, drugs of gold, separate derivatives of quinoline have antiinflammatory effect — Chingaminum (see), plaquenil (hydroxychloroquine), and also immunodepressive substances (see).
Carboxylic to - t and pyrazyl ketone these substances differ from derivatives in a number of features. So, contrary to derivatives carboxylic to - t and pyrazyl ketone they have no analgesic and febrifugal effect. In an experiment on models of an acute exudative inflammation they, as a rule, have no clear antiinflammatory activity and are effective preferential concerning a proliferative phase of an inflammation. Clinically antiinflammatory effect of drugs of gold, derivatives of quinoline and immunodepressants develops very slowly (within several weeks, months) and the hl is shown. about river concerning inflammatory processes at rheumatic diseases. In this regard drugs of gold, derivatives of quinoline and immunodepressants usually carry not to P. page, and to so-called antirheumatic means (see).
Mechanism of antiinflammatory action steroid and nonsteroid P. by page it is found out insufficiently. Consider that antiinflammatory action of P. of page of a different chemical structure is in many respects caused by influence on the processes proceeding directly in the center of an inflammation. It is established, e.g., that P. pages reduce permeability of capillaries and thanks to it reduce exudative manifestations and infiltration of the center of an inflammation phagocytes. Besides, many P. pages stabilize membranes of lysosomes and by that prevent allocation from them the lizosomalny enzymes making the damaging impact on fabrics and the mediators of an inflammation promoting activation. The braking influence on production of ATP is characteristic of steroid and nonsteroid P. of page that can lead to decrease in power ensuring inflammatory process. In the mechanism of action of P. of page their influence on processes of education and release of biologically active agents is important, apparently, the Crimea belongs a role of mediators of an inflammation (a histamine, prostaglandins, etc.). At researches much attention is paid to P.'s influence by the village on synthesis, allocation and action prostaglandins (see) and other transmutation products arachidonic to - you (cyclic endoperoxides, thromboxane, prostacyclin) which are the most active mediators of an inflammation and participate in formation of many manifestations of inflammatory reaction (e.g., pains, a hyperpermeability of capillaries, exudation, a chemotaxis of neutrophils, etc.). It is established that nonsteroid P. of page from group of derivatives carboxylic to - t (salits armor, etc.) break formation of cyclic endoperoxides, prostaglandins, thromboxane and prostacyclin from arachidonic to - you at the expense of inhibition of enzyme of cyclooxygenase — prostaglandin-endoperoxide-sintetazy (KF 1. 14. 99. 1).
There are data that derivatives carboxylic to - t inhibit cyclooxygenase by acetylation of a molecule of this enzyme. The most active inhibitors of cyclooxygenase among derivatives carboxylic to - t are indometacin, sulindak, diclofenac-sodium, Naproxenum. In an experiment on some models of an inflammation correlation between antiinflammatory activity of substances of this group and degree of inhibition them cyclooxygenases is established.
With inhibition of cyclooxygenase and reduction of products of prostaglandins and other metabolites arachidonic to - you explain not only antiinflammatory, but also some other effects of salicylates and other derivatives carboxylic to - t (e.g., febrifugal effect, analgesic action, oppression of aggregation of thrombocytes, ulcerogenic action, etc.).
Steroid P. pages also reduce synthesis of mediators of an inflammation from among metabolites arachidonic to - you, but not by inhibition of cyclooxygenase, and due to oppression of education arachidonic to - you. Concerning the mechanism of this effect of steroid P. of page there are different points of view. It agrees one of them, steroid P. of page thanks to the membrane stabilizing action interfere with education arachidonic to - you from phospholipids of cellular membranes under the influence of a phospholipase of A2. Assume also that under the influence of steroid P. the page in cells of various fabrics forms the special peptide or protein inhibiting a phospholipase of A2 and there the most breaking education arachidonic to - you of phospholipids. It is obvious also that at an aseptic inflammation (especially at the inflammation arising owing to allergic or autoallergichesky damage of fabrics) in the mechanism of antiinflammatory action of steroid P. of page their immunodepressive properties have a certain value.
Drugs of gold, derivatives of quinoline and immunodepressants on the mechanism of action differ from other P. in page. So, antiinflammatory effect of drugs of gold, perhaps, is caused by their inhibiting influence on lizosomalny enzymes, stabilization of collagen and a nek-eye oppression of immune processes (e.g., owing to disturbance of reaction antigen — an anti-body). Derivatives of quinoline have an immunodepressive effect, stabilize membranes of lysosomes, oppress a chemotaxis of leukocytes, reduce products of ATP and influence synthesis of collagen. Immunodepressants exert the oppressing impact to hl. obr. on cellular factors of immunity also suppress a proliferative phase of an inflammation due to cytostatic action.
Items of page apply to treatment of inflammatory diseases of different genesis. Most widely P. villages use as antirheumatic means. Pages apply steroid P. also to treatment of myocardites, acute and hron, nephrites, hepatitises and other inflammatory diseases of internals. Locally glucocorticoids are appointed in dermatology (e.g., at eczema, dermatitis, neurodermatitises, etc.), in ophthalmology (at a keratitis, conjunctivitis, irites, blepharites, etc.), in otorhinolaryngology (at vasculomotor and allergic rhinitises, an inflammation of outside acoustical pass, etc.).
In a combination with antibiotics or other chemotherapeutic means steroid and nonsteroid P. the page can be used for treatment inf. diseases (e.g., pleurisy, pneumonia, etc.).
Pages from group of derivatives carboxylic to - t and pyrazyl ketone widely apply nonsteroid P. in medical practice as analgesic and antipyretics. Development of ideas of the inhibiting nonsteroid P.' influence by the village on biosynthesis of metabolites arachidonic to - you and about participation of these metabolites in a pathogeny of a row patol, frustration of the noninflammatory nature was premises for development of indications to nonsteroid P.' use by the village at such frustration. E.g., villages (acetilsalicylic to - that, indometacin and some other) use nonsteroid P. as antiagregant, i.e. the means suppressing aggregation of thrombocytes. A number of scientists recommends to apply acetilsalicylic to - that and indometacin in obstetrics for the purpose of tokolitichesky therapy, etc.
Bibliography: Clinical pharmacology, under the editorship of V. V. Zakusov, page 140, M., 1978; With and r and t and to about in A. S., P r and shch e p T. P. and Yavorskaya V. E. Anti-inflammatory drugs of group of pyrazol, Tomsk, 1975, bibliogr.; Trinusf.P., Mokhort N. A. and Klebanov B. M. Non-steroidal anti-inflammatory drugs, Kiev, 1975, bibliogr.; I with and N about in with to both y M. A. and d river. Salicylates, M., 1975, bibliogr.; Mills J. And. Nonsteroidal anti-inflammatory drugs, New Engl. J. Med., v. 290, p. 781,1974; M about n-c a d a S. Vane J. R. Mode of action of aspirin-like drugs, Advanc. intern. Med., v. 24, p. 1, 1979, bibliogr.; N i-c k a n d e r R., McMahon F. G. a. R i d about 1 f about A. S. Nonsteroidal antiinflammatory agents, Ann. Rev. Pharmacol. Toxicol., v. 19, p. 469, 1979, bibliogr.; V a n e J. R. The mode of action of aspirin and similar compounds, J. Allergy clin. Immunol., y. 58, p. 691, 1976, bibliogr.