Histamine inhibitors

Proton Pump Inhibitors Histamine H2 Antagonists Other Agents Helicobacter Pylori... 

Gastrointestinal. Patients taking continuous steroid, especially in combination with a nonsteroidal antiinflammatory drug (NSAID), have an excess incidence of peptic ulcer and haemorrhage of about 1-2%. It is plainly unreasonable to seek to protect all such patients by routine prophylactic antiulcer therapy, i.e. to treat 98 patients unnecessarily in order to help two. But such therapy (proton pump inhibitor, histamine H -receptor blocker, sucralfate) is appropriate when ulcer is particularly likely, e.g. a patient with rheumatoid arthritis taking an NSAID, or for patients with a history of peptic ulcer disease. There is increased incidence of pancreatitis. 

Gastric secretory inhibitor Histamine-H2-receptor antagonist ... 

Aside from the reduction experiments with or without substrate, and other carbonyl group reactions, evidence has accrued also for the presence of a thiol group at the active site of histidine decarboxylase [12]. It has been demonstrated, for example, that approximately one thiol group per a-fi subunit is titrated with iodoacetamide or p-chloromercuribenzoate, with concomitant inactivation of the enzyme [113]. This same active-site thiol group is titrated with DTNB with loss of activity. Interestingly, the competitive inhibitors histamine and imidazole enhance the reactivity of these thiol residues toward DTNB. Upon denaturation, the enzyme... 

The dru presented in this ch )ter include the antacids, anticholinergics, GI stimulants, proton pump inhibitors, histamine H2 antagonists, antidiarrheals, antiflatulents, digestive enzymes, emetics, gallstone-solubilizing dru, laxatives, and miscellaneous dru. Some of the more common preparations are listed in the Summaiy Drug Table Dni Used in tlie Man ement of Gastrointestinal Disorders. 

In addition, Pfister and coworkers investigated 3-hydroxyflavone-6-carboxylic acids as histamine induced gastric secretion inhibitors. After condensing 3-acetyl-4-hydroxybenzoic acid (45) with a variety of aldehydes 46 to deliver the chalcones 47, these purified chalcones were then subjected to the standard AFO conditions to afford flavonols 48 in 51-80% yield. Subsequent alkylation of 48 with methyl iodide or isopropyl iodide followed by saponification of the corresponding esters gave the target compounds. 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

FIGURE 9.20 Design of multiple ligancl activity, (a) Dual histamine HI receptor and leukotriene receptor antagonist incorporating known antihistaminic properties of cyproheptadine and LTD4. (b) Joint ACE/NEP inhibitor formed from incorporating similarities in substrate structures for both enzymes. From [57],... 

Antacids are neutralizing agents. Examples are magnesium hydroxide, magnesium trisylicate and aluminium hydroxide. Prior to the introduction of histamine-H2 receptor antagonists and proton pump inhibitors, they were the standard drugs for the treatment of duodenal/ peptic ulcers. Today their clinical use is limited to the treatment of dyspepsia and the symptomatic relieve for patients with peptic ulcers. 

Stress ulcer prophylaxis is recommended in septic patients. Patients at greatest risk for stress ulcers are coagulopathic, mechanically ventilated, and hypotensive. Histamine-receptor antagonists are more efficacious than sucralfate, and proton pump inhibitors have not been compared to histamine-receptor antagonists. However, they do demonstrate equivalence in the ability to increase gastric pH.24... 

Azolides used as inhibitors for monoamine oxidase1171 or human leucocyte elastase,1181 as inductors of recessive lethal genes in Drosophila,1191 as histamine H2-receptor antagonists,1201 as anti-ulcer agents,1211 or as pharmacophores for anthelmintic, analgesic, and antimicrobial activity 1221... 

He SH, Xie H, Zhang XJ, Wang XJ. Inhibition of histamine release from human mast cells by natural chymase inhibitors. Acta Pharmacol Sin. 2004 25 822-826. 

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