Prostaglandin pharmacological inhibition

Gastric acid secretion can be pharmacologically inhibited by specific antagonists of the stimulatory receptors (histamine-Hj, muscarine-Mi/Mj, gastrin), by agonists to inhibitory receptors (prostaglandin, somatostatin), by carbonic anhydrase inhibitors, and by HVK -ATPase inhibitors. 

ARF associated with the use of non-steroidal anti-inflammatory drugs will be discussed below under pharmacologic inhibition of prostaglandin synthesis. 

Which of the following does not produce its pharmacologic effects by inhibition of prostaglandin synthesis ... 

Cashin, C. H., Dawson, W. and Kitchen, E.A. (1977). The pharmacology of benoxaprofen (2-[4-chlorophynl]-a-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with anti-inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis. J. Pharm. Pharmacol. 29 330-336. 

Misoprostol (B) is a semisynthetic prostaglandin derivative with greater stability than natural prostaglandin, permitting absorption after oral administration. like locally released prostaglandins, it promotes mucus production and inhibits acid secretion. Additional systemic effects (frequent diarrhea risk of precipitating contractions of the Liillmann, Color Atlas of Pharmacology (... 

Pharmacology The site and mechanism of the analgesic effect is unclear. APAP reduces fever by a direct action on the hypothalamic heat-regulating centers, which increases dissipation of body heat (via vasodilatation and sweating). APAP is almost as potent as aspirin in inhibiting prostaglandin synthetase in the CNS, but its peripheral inhibition of prostaglandin synthesis is minimal. 

Pharmacology Salicylates have analgesic, antipyretic, anti-inflammatory, and antirheumatic effects. Salicylates lower elevated body temperature through vasodilation of peripheral vessels, thus enhancing dissipation of excess heat. The anti-inflammatory and analgesic activity may be mediated through inhibition of the prostaglandin synthetase enzyme complex. 

Pharmacology Nonsteroidal anti-inflammatory drugs have analgesic, antipyretic, and anti-inflammatory activities. Major mechanism is believed to be inhibition of cyclooxygenase activity and prostaglandin synthesis. 

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 dioxopyrazolines are also acidic because of their enolic group (4,4-disubstituted analogues are inactive) and a recent example azapropazone (apazone) (184) inhibits prostaglandin synthesis. Its pharmacological properties are like those of phenylbutazone and it is also uricosuric. Anti-inflammatory 1,2-benzothiazine 1,1-dioxides such as piroxicam (185 R = 2-pyridyl) also have an acidic enolic group whose anion can be stabilized by... 

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,... 

Prostaglandins are biosynthesized from arachidonic acid, an unsaturated fatty acid containing four double bonds. The enzyme prostaglandin endoperoxide synthase converts arachidonic acid to PGH2, which serves as the precursor for prostaglandins and related compounds. Aspirin exerts its pharmacological effect by inhibiting this enzyme. 

Chintakunta VK, Akella V, Vedula MS et aL (2002) 3-0-Substituted benzyl pyrazidone derivatives as COX inhibitors. Eur J Med Chem 37 339-347 Coleman RA, Smith WL, Narumiya S (1994) VIII. International union of pharmacology classification of prostanoid receptors Properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46 205-229 Copeland RA, Williams JM, Giannaras J et al. (1994) Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proc Natl Acad Sd USA 91 11202-11206... 

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