Prostaglandins and Related Compounds Prostaglandins and Related Compounds. Objective : Definitions, Synthesis, Types & Drugs interaction-Functions.

Prostaglandins (PGs) and related compounds; the Thromboxanes (TXs)and Leukotrienes (LTs) are collectively referred to Eicosanoids which reflect their origin from PUFAs with 20 Carbons. They are considered as hormones, but are actually not true hormones because they are produced in almost all tissues (not specialized glands), act locally (not transported via the blood and act at specific target tissues like T4, insulin). These compounds are produced in very small amounts, but are potent compounds and exert a wide range of physiological (vasodilator, platelet aggregation,…, etc) and pathological actions ( fever, heat, redness,…, etc.).

The PGs and TXs are derived from the dietary essential FAs, the Linoleic acid C18 ;1. Linoleic acid is elongated and desaturated to arachidonic acid C20;3 which is a component of phospholipids of cell membranes. The enzyme Phospholipase A2 acts on C M to remove its associated arachidonic acid into the cells. The released arachidonic acid is converted firstly into PGH2 by PGH synthase enzyme, which become the precursor for other types of PGs and TXs. PGH synthase enzyme has both: Cyclooxyganse (Fatty acid cyclooxyganse COX), and peroxidase activity. The most important is the COX which present in two types, the COX1 and COX2.

COX-1 is constitutive enzyme in most tissues, and is essential for maintenance of normal GIT, Kidney, and platelet aggregation (so its inhibition leads to pathological problems). The COX-2 is inducible enzyme (normally is dormant) in a number of tissues in response to products of inflammation and immune system (such as histamine, serotonin,.., etc), and the increased of PGs synthesis by induced COX-2 is responsible about fever, redness, rash, swelling, pain, and heat. Drugs and PGs synthesis: Cortisol is steroidal anti-inflammatory drug that inhibits Phospholipase A2 and reduce the availability of arachidonic acid for PGs synthesis.

Other type of drugs, the NSAIDS nonsteroidal anti-inflammatory drugs, such as Aspirin, Indomethasen, brufen…, inhibit both COX-1 & COX-2. In these cases COX-1 which is essential for normal health is absent and damage to GIT, kidney, and impairment of blood clotting will occur, that is the basis of high dose toxicity of Aspirin . New generation of drugs, the coxib (as celecoxib) inhibit selectively the COX-2 with reducing the pathologic inflammatory complications while maintaining the normal COX-1 action and health body system.

TXs such as TXA2 is produced from arachidonic acid by activated platelets stimulating the thrombi formation (blood clots) by aggregation of circulating platelets and vasoconstriction. In opposite, PGI2 the prostacyclin inhibits the aggregation of platelets and induce vasodilatation at vascular endothelial of site. Balance between these two actions is the limit thrombi formation at site of vascular injury. Aspirin in low continuing doses is used to lower the risk of CHD (or IHD ischemic heart diseases) by inhibiting COX-1 of platelets but not that of endothelial. LT leukotrienes produced by leukocytes, platelets, heart,..,etc, from arachidonic acids by lipooxyganse enzyme and not by COX, not inhibited by NSADS and are mediators of Asthma and inflammation.