Prostaglandin synthesis, inhibition

Bradykinin stimulates natriuresis and, through stimulation of prostaglandin synthesis, inhibits the actions of antidiuretic hormone (ADH), thereby inhibiting water retention. Bradykinin further improves insulin sensitivity and cellular glucose utilization of skeletal muscle cells in experimental models. This, however, appears not to be relevant in the clinical context. 

TABLE 36.2 Adverse Effects of NSAIDs - Relationship to Prostaglandin Synthesis inhibition and Cyclooxygenase Isoforms... 

Clinical use Metamizol is the water-soluble sodium sulfonate of amidopyrine. After oral administration it is rapidly hydrolyzed to the active 4-methyl-amino-antipyrine and metabolized to various metabolites (Levy et al., 1995 scheme 47). Metamizol has strong analgesic, spasmolytic and antipyretic action, but no anti-inflammatory properties. The exact mechanism of action is unknown but may include inhibition of prostaglandin synthesis. Inhibition of both COX isoenzymes has been demonstrated, although only in extremely high concentrations, thus questioning the relevance of this activity. 

BoerWH, Fransen R, Boer P, Roos R de, Koomans HA. Prostaglandin synthesis inhibition stimulates lithium reabsorption in Henle s loop in rats. Kidney Int 1993 43 301-306. 

Carty TJ, Stevens JS, Lombardino JG, et al. Piroxicam, a structurally novel anti-inflammatory compound. Mode of prostaglandin synthesis inhibition. Prostaglandins 1980 19 671-682. 

Strausser HR, Humes JL. Prostaglandin synthesis inhibition Effect on bone changes and sarcoma tumor induction in balb/c mice. Int J Cancer 1975 15 724-730. 

Brune, K. Beck, W.S. Geisslinger, G. Menzel-Soglowek, S. Peskar, B.M. Peskar, B.A. Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition. Experentia 1991, 47, 257-261. 

Silberbauer K, StanekB, Tempi H. Acute h3rpotensive effect of captopril inmanmodified by prostaglandin synthesis inhibition. BrJ Ctin Pharmacol (1982) 14, 87S-93S. 

Mason, R.T., Coghlan, J.P., Denton, D.A., Graham, W.F., Humphery, T.J., Scoggins, B.A. and Whitworth, J.A. (1984). Prostaglandin synthesis inhibition with indomethacin in ACTH-induced hypertension. ]. Cardiovasc. Pharmacol, 6, 288-292... 

Colina-Chourio, J., McGiff, J.C. and Nasjletti, A. (1979). Effect of indomethacin on blood pressure in the normotensive unanesthetized rabbit Possible relation to prostaglandin synthesis inhibition. Clin. Sci., 57, 359-365... 

Orehek J, Douglas JS, Bouhuys A (1975) Contractile responses of the guinea pig trachea in vitro modification by prostaglandin synthesis-inhibiting drugs. J Pharmacol Exp Ther 194 554-564... 

Nonimmunologic contact urticaria (NICU) occurs in individuals not sensitized to the contactant, i.e., almost any normal subject. The mechanism of action is the result of a direct release of vasoactive substances, which causes a localized response [20]. Prostaglandins are mediators in the reaction to at least benzoic and sorbic acids and to methyl nicotinate, and systemic or topical inhibitors of prostaglandin synthesis inhibit the reaction to these substances [21-23]. Ultraviolet radiation (UVB and UVA) has also been shown to inhibit NICU reactions to some substances [24]. The NICU reaction is often redness without edema rather than a real wheal-and-flare reaction. The appearance of clinical signs depends mainly on the duration of exposure, the concentration of the contactant and other factors, such as rubbing or scratching. The reaction usually remains localized and systemic reactions are probably... 

Occurrence in the Convolvulaceae. The phenylethene 4-vinylguaiacol (Fig. 6.3) was characterized as another constituent of the leaves of Ipomoea pes-caprae. It was detected by the same procedure as described above for eugenol, thus including its prostaglandin synthesis inhibiting properties (Pongprayoon et al. 1991). 

Effects with the autonomous nervous system have also merited attention. Over the cardiovascular system anti arrhythmic 341), antieschemic (555), antihemorrhagic 348), antifibrillatory 346), PAF inhibition 435), vasorelaxant 449), and hypotensive activities (552) are some of the important biological effects reported for the protober-berine alkaloids in the period covered by this review. Also important to mention are the metabolic effects hypoglycemic 351,404), antihypercholesterolemic 350), bone resorption inhibition (5(56), osteoclast formation inhibition (566), lipase and lipogenesis inhibition 412,414), and prostaglandin synthesis inhibition 438), are a few of the reported activities related to metabolism. 

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