Eicosanoid Pharmacology

Eicosanoids are ceU-regulating polyunsaturated fatty acids primarily synthesized from arachidonic acid and released by the action of phospholipase A2 from lipids in ceU membranes. 

Eicosanoids are present in low concentrations in most cells but are synthesized and released on demand in response to stimuli, including IgE-mediated reactions, inflammatory mediators, trauma, heat, and toxins. 

Eicosanoids interact with specific receptors, which are G-proteins coupled to second messenger effector systems. 

Prostaglandins (PCs) are cytoprotective in the stomach, dilate renal vasculature, contract the uterus, and maintain the ductus arteriosus. Thrombaxane (TxA ) causes platelet aggregation. Gl PCs and platelets TxA s are synthesized by COX 1 (constitutive). 

COX 2 (inducible) synthesizes PCs involved in inflammation, fever, and pain. Both enzymes synthesize renal PCs - t RBF. 

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Eicosanoids are formed from 20-carbon polyunsaturated fatty acids and make up an important group of physiologically and pharmacologically active compounds known as prostaglandins, thromboxanes, leukotrienes, and lipoxins. 

Campbell, W.B. and Halushka, P. V., Lipid-derived autacoids eicosanoids and platelet-activating factor, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill,... 

Foegh, M.L. and Ramwell, P.W., The eicosanoids prostaglandins, thromboxanes, leukotrienes and related compounds, in Basic and Clinical Pharmacology, 8th ed., Katzung, B.G., Ed., Lange Medical Books/McGraw-Hill, New York, 2001, chap. 18. 

Nicosia S, Patrona C. Eicosanoid biosynthesis and action novel opportunities for pharmacological intervention. EASEB J 1989 3 1941-8. 

Smith WL. The eicosanoids and their biochemical mechanisms of action. Biochem J 1989 259 315-324. Sweetman S, editor. Martindale the complete drug reference. 35th ed. London Pharmacentical Press 2007. Tripathi KD. Essentials of medical pharmacology. 5th ed. 

Figure 8.9 Prostaglandins and leukotrienes are potent eicosanoid lipid mediators, derived from phospholipase-released arachidonic acids, that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and pharmacological actions are inhibited by clinically relevant nonsteroidal anti-inflammatory drugs.

The pharmacological effects of the prostaglandins and TXAj comprise many different activities—in fact too many. The lack of specificity of their activities implies a number of side effects which preclude the clinical application of several highly active natural prostaglandins, necessitating the development of selective synthetic compounds. The following effects of prostaglandins/eicosanoids are known and are summarized in table 8.3. 

Basic and Clinical Pharmacology > Chapter 18. The Eicosanoids Prostaglandins, Thromboxanes, Leukotrienes, Related Compounds > ... 

Smooth muscle-relaxing prostaglandins such as PGE1 enhance penile erection by relaxing the smooth muscle of the corpora cavernosa (see Clinical Pharmacology of Eicosanoids). 

EICOSANOID. Any of a number of biochemically active compounds resulting from enzymic oxidation of arachidonic acid. e.g.. prostaglandins, thromboxanes, prostacyclin, and leukotrienes As a group they compose what is known arachidonic acid cascade. They have many pharmacological and medical possibilities. 

Some, but not all, of the pharmacological effects of eicosanoids are mediated through alterations in the concentration of cyclic adenosine monophosphate (cyclic AMP). For example, prostaglandins Ej and E2 inhibit platelet aggregation by increasing the cyclic AMP concentration. Conversely,... 

The eicosanoids act in an autocrine and paracrine fashion. These ligands bind to receptors on the cell surface, and pharmacologic specificity is determined by receptor density and type on different cells. A number of the membrane receptors and their subtypes have been cloned. All of these receptors appear to be G protein-linked properties of the best-studied receptors are listed in Table 18-1. 

The effects of prostaglandins on uterine function are of great clinical importance. They are discussed below. (See Clinical Pharmacology of Eicosanoids.)... 

PGE and PGF derivatives lower the intraocular pressure. The mechanism of this action is unclear but probably involves increased outflow of aqueous humor from the anterior chamber via the uveoscleral pathway (see Clinical Pharmacology of the Eicosanoids). 

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