Pharmacology of Eicosanoids

The action of eicosanoids is both, intracellular (autocrine) and intercellular on the cells immediately adjacent to their site of origin (paracrine). However, they are not transported like the endocrine hormones through the bloodstream to a distant target. In particular, the eicosanoids participate in  

Corresponding to their omnipresence, they possess also broad therapeutic interest. However, as a rule, these therapeutic agents are derivatives ofthe natural products, since the latter are metabolised very rapidly. In addition, through structural modification it is possible, to tune the selectivity of the intended activity. 

Prostanoids play a significant role in diseases of the gastrointestinal tract. Their cytoprotective and accelerated healing effects make them the remedy of choice for the treatment of stomach ulcers. The prostaglandin-Ej derivative misoprostol (Cytotec , Searle) serves, for example, as an ulcer drug. 

Prostaglandins of the A- and E-series lower the blood pressure. Thromboxanes and carbacyclins are used for the treatment of cardiovascular diseases. Corresponding drugs are e.g. alprostadU (Prostavasin , Schwarz Pharma, Ono Pharmaceutical) or Uoprost (Ilomedin , Bayer/Schering). Prostaglandins of the E- and F-series, like dinoprostone (Minprostin E2 , Pharmacia and Upjohn/Pfizer) and dinoprost (Minprostin F2 , Pharmacia and Upjohn/Pfizer) lead to contractions of the uterine smooth muscle, and are used for termination of pregnancy and in obstetrics. 

Prostaglandins of the E- and D-series reduce intraocular pressure, and thus offer attractive therapeutic options for the treatment of glaucoma. Marketed drugs are, for example, latanoprost (Xalatan , Pfizer) and travo-prost (Alcon). 

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

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

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,... 

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). 

M. Vellini, D. Desideri, A. Milanese, C. Omini, L. Daffonchio, A. Hernandez, and G. Brunelli. Possible involvement of eicosanoids in the pharmacological action of bromelain. Arzneim. ForschJDrug Res. 56(1) 110 (1986). 

In the first part the biosynthesis of fatty acids in skin with its role in barrier function as well as the role of dietary fatty acids on skin cell function and in the treatment of inflammatory skin diseases is presented. The second part deals with skin as a source of proinflammatory eicosanoids, especially with the keratinocyte as a major cellular source. Metabolism of eicosanoids in skin, its role in psoriasis and atopic dermatitis as well as pharmacological inhibition of eicosanoid biosynthesis is reviewed. 

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,... 

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. 

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. 

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