H2-Histamine. antagonists

Very recently, a very bold chemical model for histamine H2-receptors has been proposed using [18]aneN6-3H+ 84), which can chemically recognize histamine, histamine H2-agonists, and histamine H2-antagonists such as cimetidine XII or ranitidine XIII that are currently in world-wide use for treatment of peptic ulcers 85). 

FIGURE 1.7 Key compounds synthesized to eliminate the efficacy (burgundy red) and enhance the affinity (green) of histamine for histamine H2 receptors to make cimetidine, one of the first histamine H2 antagonists of use in the treatment of peptic ulcers. Quotation from James Black [10]. 

FIGURE 8.20 Drugs as subsets of clinical profiles. While burimamide, cimetidine, and metiamide are all active histamine H2 antagonists with ulcer healing activity burimamide lacks a suitable toxicity and pharmacokinetic profile and cimetidine is adequately absorbed but still toxic. Only metiamide fulfills the requirements of a clinically useful drug. 

Specific anticholinergic drug are occasionally used in die medical treatment of peptic ulcer. These drug have been largely replaced by histamine H2 antagonists, which appear to be more effective and have fewer adverse drug reactions. 

These drug inhibit die action of histamine at histamine H2 receptor cells of die stomach, which then reduces die secretion of gastric acid and reduces total pepsin output. The decrease in acid allows the ulcerated areas to heal. Examples of histamine H2 antagonists include cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid Pulvules), ranitidine (Zantac). 

Adverse reactions of the histamine H2 antagonists include dizziness, somnolence, headache, confusion, hallucinations, diarrhea, and impotence (that is reversible when the drug is discontinued). Adverse reactions are usually mild and transient. 

The histamine H2 antagonists are contraindicated in patients with a known hypersensitivity to the dragp. 

HISTAMINE H2 ANTAGONISTS. The nurse administers ranitidine and oral cimetidine before or with meals and at bedtime Nizatidine and famotidine are given at bedtime or, if twice-a-day dosing is prescribed, in the morning and at bedtime. These drugp are usually given concurrently with an antacid to relieve the pain. In certain situations or disorders, cimetidine and ranitidine may also be given by intermittent IV infusion or direct IV injection. 

HISTAMINE H2 ANTAGONISTS. During early therapy with these drug, the patient may experience dizziness or drowsiness. The patient may require assistance with ambulation. These reactions usually must be tolerated, but the nurse reassures the patient that they will disappear after several days of therapy. 

Smit, M. J., Leurs, R., Alewijnse, A. E. et al. (1996). Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors. Proc. Natl. Acad. Sci. USA 93, 6802-7. 

In the same article data set was expanded to include some 20 potent histamine H2 antagonists. Analysis of these compounds indicated the significance of lipophilicity and hydrogen bonding for penetration of BBB, since a good... 

Drugs that may affect sulfonylureas include androgens, anticoagulants, azole antifungals, barbiturates, beta blockers, calcium channel blockers, charcoal, chloramphenicol, cholestyramine, ciprofloxacin, clofibrate, corticosteroids, diazoxide, estrogens, ethanol, fluconazole, gemfibrozil, histamine H2 antagonists, hydantoins,... 

Drugs that may affect tricyclic compounds include barbiturates, carbamazepine, charcoal, cimetidine, haloperidol, histamine H2-antagonists, MAO inhibitors,... 

Drugs that may be affected by antacids include allopurinol, amphetamines, benzodiazepines, captopril, chloroquine, corticosteroids, dicumarol, diflunisal, digoxin, ethambutol, flecainide, fluoroquinolones, histamine H2 antagonists,... 

Pharmacology Histamine H2 antagonists are reversible competitive blockers of histamine at the H2receptors. They also inhibit fasting and nocturnal secretions, and secretions stimulated by food, insulin, caffeine, pentagastrin, and betazole. 

Pharmacokinetic Properties of Histamine H2 Antagonists 2 Bioavailability Time to peak Half-life Protein Metabolized... 

Drugs that may affect histamine H2 antagonists include antacids, anticholinergics, metoclopramide, and cigarette smoking. Drugs that may be affected by histamine H2... 

Drugs that may affect ketoconazole include antacids, didanosine, histamine H2 antagonists, isoniazid, sucralfate, proton pump inhibitors, and rifampin. Drugs that may be affected by ketoconazole include oral anticoagulants, corticosteroids, cyclosporine, protease inhibitors, tricyclic antidepressants, carbamazepine. 

Drugs that may affect delavirdine include the following Anticonvulsants, antacids, clarithromycin, didanosine, fluoxetine, histamine H2 antagonists, ketoconazole,... 

Histamine H2 antagonists these relieve persistent heartburn and are generally safe and effective in acid reflux without mucosal damage. There is little reason to prefer one clinically over another. Treatment has to be continued indefinitely. They are relatively ineffective in established inflammation. 

Il.b.l.1. Adverse effects of anti-secretory treatment. Histamine H2 antagonists and proton pump inhibitors are very safe as well as effective treatments. Cimetidine has small effects on hepatic drug metabolism which are only of clinical signiflcance with drugs used in doses close to toxic levels, notably phenytoin, aminophylline and warfarin. Other adverse effects such as headache, rash and thrombocytopenia are rare. 

A. If the precipitant can be withdrawn then an-tisecretory treatment with a histamine H2 antagonist or proton pump inhibitor, or misoprostol (an antisecretory and mucosally protective prostaglandin) for a month may be enough to induce ulcer healing. 

D. Gastrointestinal bleeding is usually due to acute erosions. Histamine H2 antagonists reduce the risk. 

Of the thiatriazines, the 1,2,4,6-system has been the most studied. There has been particular interest in TV-alkyl-1,2,4,6-thiatriazine 1,1-dioxides because of their herbicidal, fungicidal, and histamine H2-antagonist activity (86TL123,87S170). The preparation of l-chloro-l,2,4,6-thiatriazines (576) by reaction of imidoylamidines (575) with an excess of sulfur dichloride was reported (80JOU1303). 

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