GASTRIC SECRETION INHIBITORS

GASTRIC SECRETION INHIBITORS act at some stage in the control process to inhibit the enzymic or gastric acid secretions of the stomach, with the latter being a major therapeutic target. The neuronal, hormonal and paracrine control of gastric acid secretion from the parietal cells of the gastric mucosa is complex. The pathways involved include acetylcholine via the parasympathetic innervation of the stomach, the hormone gastrin. the paracrine agent histamine and possibly the paracrine hormone gastrin-releasing peptide. Anticholinergic agents have not proved very valuable in the long-run, having a limited ability to reduce acid secretion at doses that can be tolerated in view of widespread side-effects. Some more recently developed agents show gastric-selectivity (they are Mrcholinoceptor-preferring ligands, which may be the reason for their selectivity), e.g. pirenzepine and telenzepine: see muscarinic cholinoceptor antagonists. Gastrin receptor antagonists and gastrin-releasing peptide antagonists have now been developed for experimental use, but it is not yet clear if either will be useful clinically. See BOMBESIN RECEPTOR ANTAGONISTS; CHOLECYSTOKININ RECEPTOR ANTAGONISTS. Histamine H2-receptor antagonists Read more […]

CYCLOOXYGENASE INHIBITORS

CYCLOOXYGENASE INHIBITORS bind reversibly or irreversibly to the enzyme cyclooxygenase (originally referred to as the prostaglandin synthase system or ‘prostaglandin H2 synthase’; (PGHS)-l and (PGHS)-2). Members of the prostaglandin family have a number of proinflammatory or hyperalgesic actions, and consequently many cyclooxygenase inhibitors are used as anthnflammatories and ANALGESICS. Prostanoids are members of the eicosanoid family of phospholipid mediators, and are comprised of the thromboxanes and the prostaglandins, both of which are formed by the complex cyclooxygenase system. They share common precursors in the form of a series of unstable cyclic endoperoxides. The first stage of the transformation of arachidonic acid has the enzyme endoperoxide synthase oxygenate arachidonate, followed by cyclization to give a cyclic endoperoxide called PGG2. These reactions are inhibited by cyclooxygenase inhibitors. Subsequently, PGG2 is converted by a peroxidase action to PGH2. This is a common precursor for a number of different pathways, forming prostacyclin (by prostacyclin synthase), the various prostaglandins or thromboxanes (by thromboxane synthase). See THROMBOXANE SYNTHASE INHIBITORS. The conversion depends Read more […]

ANTIULCEROGENIC AGENTS

ANTIULCEROGENIC AGENTS (or ulcer-healing drugs) are used to promote healing of ulceration of gastric and duodenal peptic ulcers. A number of classes of drugs may be used. See also gastric secretion inhibitors. First, the HISTAMINE H2-ANTAGONISTS are very effective and have considerable usage, e.g. cimetidine. famotidine, nizatidine and ranitidine. These agents decrease gastric acid secretion and promote healing and may be used to treat dyspepsia and oesophagitis of a number of etiologies. Acid production is also very effectively reduced by the newer agents, the proton pump inhibitors, e.g. omeprazole (see GASTRIC PROTON PUMP INHIBITORS). Anticholinergic drugs are only really suitable in the case of agents that show some gastric-selectivity, e.g. pirenzepine and telenzepine (see muscarinic cholinoceptor ANTAGONISTS). They work by reducing the secretion of peptic acid by the stomach mucosa. Some prostaglandin analogues are effective in protecting the mucosa, and are incorporated into some preparations of NSAIDs to offer concurrent protection (though they may cause unacceptable stimulation of the ileum), e.g. misoprostol. (see prostanoid receptor agonists) . Bismuth-containing antacid preparations have been Read more […]