Histamine H2 blockers

Indigestion, heartburn, and nausea are common side effects of valproate therapy. Use of the divalproex sodium preparation will help mitigate these effects. Patients may also be encouraged to take their doses with food. The symptomatic use of histamine H2 blockers, such as famotidine, is sometimes warranted. In most cases, however, dyspepsia is transient and not severe. Pancreatitis is a rare occurrence in patients receiving relatively high doses of valproate. If vomiting and severe abdominal pain develop during valproate therapy, serum amylase levels should be determined immediately. 

Work from other laboratories, some of which is discussed in Chapter 9, later showed 2-aminopyrimidones could fulfill the same functions in histamine H2 blockers as do thioureas and modified guanidines in the initial compounds many of these agents are interestingly devoid of histamine-like nuclei. Oxmetidine (66-2) represents a hybrid in that it includes moieties from both series. The p5Timidone-2-thiol (66-1) is prepared in a manner analogous to that which will be described in Chapter 9 for lupitidine condensation of this with the intermediate (63-5) leads to the replacement of the thiol by the terminal amino group. There is thus obtained oxmetidine (66-2) [69]. 

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). 

Antihistamine drags are classified as antagonists of Hj and receptors, and quantitatively speaking Hj antagonists dominate. Moreover, the term antihistamine drag is associated more with Hj antagonists. H2 blockers exhibit a specific effect on histamine receptive sites located in walls of the stomach and they significantly increase secretion of hydrochloric acid. 

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,... 

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. 

The effects of histamine on body tissues and organs can be diminished in four ways inhibition of histamine synthesis, inhibition of histamine release from storage granules, blockade of histamine receptors, and physiological antagonism of histamine s effects. Of these approaches, only the inhibition of histamine synthesis has not been employed clinically. The focus of this chapter is on Hi histamine receptor antagonists it provides a brief overview of the H2 blockers and the inhibitors of histamine release. More details can be found in Chapters 39 and 40. 

Cimetidine, the first released H2-blocker, like histamine, contains an imidazole ring structure. It is well absorbed following oral administration, with peak blood levels 45 to 90 minutes after drug ingestion. Blood levels remain within therapeutic concentrations for approximately 4 hours after a 300-mg dose. Following oral administration, 50 to 75% of the parent compound is excreted unchanged in the urine the rest appears primarily as the sulfoxide metabolite. 

The answer is d. (Hardman, p 906.) Cimetidine slows the metabolism of Ca channel blockers, which are substrates for hepatic mixed-function oxidases. Inhibition of cytochrome P450 activity is peculiar to cimetidine and is not a mechanism of action of other histamine 2 (H2) blockers. 

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. 

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

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. 

Mast cells and enterochromaffin-like cells found in the interstitium and among parietal cells contain histamine, which acts on parietal cell receptors to stimulate the release of hydrochloric acid. The histamine receptor on parietal cells is designated as H2 and is blocked by H2 blockers such as cimetidine which are widely used to treat peptic ulcers. 

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