Histamine H2 Receptor Blockers

Histamine H2-receptor blockers -idine Cimetidine, ranitidine Gastric ulcers (27)... 

The bioslurry treatment successfully removed several of the PhC to non-detectable levels after 26 days three histamine H2-receptor antagonists (ranitidine, famotidine, cimetidine), two (1-blockers (atenolol, sotalol), one barbiturate (butalbital) and one antidiabetic compound (glibenclamide). The elimination of the sulfonamide antibiotics sulfapyridine (100%), sulfamethazine (91.0%) and... 

This lack of complete effectiveness led to the hypothesis that a second type of histamine receptor existed. In 1972, Black et al. (55) discovered a new series of antagonists which they called H2 receptor blockers. Burimamide was the first highly effective H2 blocker, but it was poorly absorbed orally. The modified compound, metiamide, had better absorption but was found to cause granulocytopenia (57.58). Finally, cimetidine was tested and found to be a potent and relatively non-toxic antagonist (59). Cimetidine is now widely used clinically to treat duodenal ulcers, Zollinger-Ellison Syndrome and other gastric hypersecretory diseases (32). 

Hf and H Receptors. Histamine exerts its actions by binding to receptors on cell membranes. Two types of histamine receptors, the Hi and H2 receptors, are known specific agonists and antagonists exist for each of these receptors. Black et al. (55) differentiated H and H2 receptors with the compounds, 2-methylhistamine and 4 methylhistamine. 2-Methylhistamine is active on tissues with H receptors 4-methylhistamine is active on tissues with H2 receptors. Classical antihistaminic drugs were developed in the 1930 s these compounds block H but not H2 receptors. Among the clinically used H -blockers are derivatives of ethanolamine, ethylenediamine, alkylamine, piperazine and phenothiazine (32). These agents are valuable in the treatment of... 

The development of H2-receptor antagonists was based on the observation that H4 antagonists had no effect on histamine-induced acid secretion in the stomach. Molecular manipulation of the histamine molecule resulted in drugs that blocked acid secretion and had no H4-agonist or antagonist effects. Like the other histamine receptors, the H2 receptor displays constitutive activity, and some H2 blockers are inverse agonists. 

Oral 400 to 800 mg combined hydroxides per tablet, capsule, or 5 mL suspension H2 Histamine Receptor Blockers Cimetidine (generic, Tagamet, Tagamet HB )... 

H2-histamine receptor blockers alone or together. Hyperuricaemia, due to cell destruction, is prevented by allopurinol and iron and folate deficiency by replacement doses (due to the rapid response of the myeloproliferative erythron). Aspirin remains controversial. Low-dose aspirin (for antiplatelet action) may be used if the platelet coxmt remains high or thrombosis occurs despite the above treatment but is best avoided in patients with a history of haemorrhage. 

Synonyms Zantac Histamine blocker Antacid N,N-Dimethyl-5-(2-(l-methylamino-2-nitrovinyl-amino)-ethylthiomethyl)furfurylamine Chemical/Pharmaceutical/Other Class A competitive inhibitor of the H2 receptor located on the gastric parietal cells Chemical Structure ... 

Even though most stomach ulcers are treated by gastric acid secretory inhibitors or H2-receptor (histamine) blockers such as cimetidine, the simulation technique has led to formulations that produce bismuth patches on ulcers at other sites having other pH values. However, the optimization of conditions for ulcer healing is very difficult using clinical trials because of the vagaries of ulceration and of responses to therapy, some 80% of ulcers reoccurring within a year. 

Histamine is in mast cells, basophils, and platelets. Human skin mast cells express H H2, and H4 receptors, but not H3 receptors. Hi and H2 receptors are involved in wheal formation and erythema, whereas only Hi-receptor agonists cause pruritus. Complete blockade of Hi-receptors does not totally relieve itching, and combinations of Hi and H2 blockers may be superior to H, blockers alone. 

These observations were confirmed and extended by Hayden, Thomas and West with reports showing that Cu(II)2(aspirinate)4 and Cu(IIXsaUcylate)2 were more efifective in the aspirin-exacerbated Shay ulcer model than either the H,(Mepyramine) or H2(Metiamide) histamine receptor blockers, as shown in Table 6.19 [263]. It was also shown that Cu(II)(saUcylate)2 was more... 

There are two types of histamine receptors Hj and H2. H2 receptors cause an increase in gastric secretions and are not involved in this response. The differences are illustrated in the charts. (See Antihistamine (Hj blocker) chart and Antihistamine Use to Treat Allergic Rhinitis chart.)... 

---