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Prostaglandins and their synthetic derivative drugs

Prostaglandins are group of the biogenous physiologically active agents which are contained in bodies and body tissues. The name "prostaglandins" comes from the Latin name of a prostate (glandula prostatica), where as earlier assumed, prostaglandins are formed.

On chemical structure prostaglandins (PG) belong to the class of fatty acids. Is the cornerstone of their building so-called prostanoyevy [7-(2 octylcycloheptyl) geptanonoyevy] the acid consisting of a 20-chlenny carbon chain which part is included in a cyclopentanoic ring. Biogenous predecessors of prostaglandins in an organism are arachidonic also some other unsaturated fatty acids (digomolinolenovy) which are contained in phospholipids of cellular membranes. Synthesis of prostaglandins happens with the participation of microsomal enzymes.

From tissues of animals a number of natural prostaglandins is allocated. On features of the chemical building prostaglandins divide into the groups having the Latin E, F, A, B indexes, etc., and on the subgroups having additional digital designations (PGE M1, PGE M2, etc.). Figures mean the number of double bonds in a side chain of a molecule of any given prostaglandin. For the medical purposes prostaglandins received originally from natural sources (some types of corals, etc.). Now prostaglandins-drugs and their derivatives receive in the synthetic way. Prostaglandins have many-sided physiological (pharmacological) activity. Consider that they are gormonopodobny substances ("local" hormones) which production reguliruyut cellular metabolism.

Characteristic is influence of a number of prostaglandins on sokratitelny activity of smooth muscles, secretion, blood circulation (including microcirculation) and also other functions of an organism. Prostaglandins of the E, F and A, PGE1 and PGE2 groups are most active render broncholitic, and PGE M2 Aa - bronkhokonstriktorny action; PGE M1 slows down secretion of gastric juice, discharge of hydrochloric acid and pepsin; PGE M2 reduces the peripheric resistance of vessels and reduces arterial blood pressure, increases permeability of capillaries; PGA M 1 and PGA M2 also reduce vascular resistance and lower arterial blood pressure.

Vascular effects of prostaglandins connect with their direct action on unstriated muscles of vessels and the modulating influence on an adrenergic innervation. Prostaglandins strengthening adrenergic influences cause vasoconstriction; the weakening adrenergic influences - their expansion. Believe also that effect of prostaglandins is connected with increase (or reduction) the intracellular maintenance of tsAMF. Prostaglandins take part in transfer of nervous impulses in different parts of the nervous system, making the modulating impact on synoptic processes.

Prostaglandins of the E and F groups have the strong stimulating impact on myometrium which is shown in the relation of both a non-pregnant, and pregnant uterus in all durations of gestation. In physiological conditions they are of great importance for reproductive function; are considered as "intermediaries of an ovulation"; promote regulation of processes of implantation, the beginning of patrimonial activity, etc. Prostaglandins play an important role in the mechanism of action of a number of medicines. It is established that acetylsalicylic acid, indometacin, Ortophenum and other non-steroidal anti-inflammatory drugs inhibit biosynthesis and physiological activity of prostaglandins.

Originally the greatest attention from the physiological and pharmacological points of view was attracted by prostaglandins of the E and F group. E and F prostaglandins found application in medical practice as "uterine" (oxytocic) means (see the Means stimulating uterus muscles). On the basis of prostaglandins also means of other pharmacological groups are created (see Alprostadil, Mizoprostol). Now great attention is given not only to prostaglandins, but also a row related by it products of metabolism of arachidonic acid. It became clear that depending on a way of enzymatic biotransformation of arachidonic acid from it various highly active connections are formed.

With the participation of cyclooxygenase enzyme along with prostaglandins, prostacyclins (are produced with participation prostacyclin-sintetazy) and thromboxanes (with participation thromboxane-sintetazy). The prostacyclin synthesized mainly in an endothelium of vessels and also coming to the blood course from lungs is especially strong endogenous inhibitor of aggregation of thrombocytes and abhesive means. Its anti-aggregation action is connected with activation of adenylatecyclase and increase in maintenance of tsAMF in thrombocytes. It strengthens also anti-coagulative effect of heparin. Prostacyclin has high vasodilating and hypotensive activity.

Thromboxane as opposed to prostacyclin has strong pro-aggregation activity and has the significant vasopressor effect. Believe that the balance between prostacyclin and thromboxane plays an important role in ensuring haemo static balance and function of thrombocytes and that disturbance of this balance towards exceeding activity of thromboxane contributes to the development of thromboses and atherosclerotic changes of vessels.

Under the influence of lipoxygenase enzyme 5 in the course of metabolism of arachidonic acid other group of highly active connections - leukotrienes (LT) is formed. They are called so because were originally open in leukocytes and have the conjugated triyenovy structure. Connections of this group (LTV, LTS) play an important role in development of inflammation and a bronkhiolospazm. LTS is a component of the so-called slowly reacting anaphylaxis substance. Leukotrienes unlike prostaglandins have no in structure of a cyclic kernel. Prostaglandins, leukotrienes and related connections are called eicosanoids as they are derivatives of eykozanoyevy acids: eykozotriyeniyevy (digomo-linolenic), eykozotetrayenoyevy (arachidonic), etc.

Due to the high physiological activity of these endogenous connections already from the moment of their discovery, identification of structure and synthesis (70th years) the foundation was laid for their use as medicines. Originally F and E prostaglandins found application as uterine means (see Dinoprost, Dinoprostonum). Now different connections of this group began to use in other fields of medicine (see Prostenon, Alprostadil, Mizoprostol). A lot of work on creation of new medicines on the basis of prostaglandins and prostacyclins is conducted (broncholitic, anti-aggregation, antihypertensive, anti-sclerous, etc.). Also search of antagonists of the leukotrienes counted on receiving anti-inflammatory and bronchodilatory drugs is carried out.

Alprostadil
Misoprostol
Diseases

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