Ulcer treatment drug, cimetidine

Traditional or Hj antihistamine drugs block many effects caused by histamine however, it turns out that they are not able to withstand events mediated by H2 receptors, in particular excess gastric juice secretion. In 1977 an H2-receptor antagonist, cimetidine, was proposed, which revolutionized stomach ulcer treatment. Later on, ranitidine was proposed, followed by drugs with minor structural and pharmacological differences such as famotidine and nizatidine. 

The discovery and development of cimetidine and ranitidine provided a revolution in the medical treatment and management of peptic ulcer disease. Subsequently, many pharmaceutical companies became involved in research programs to discover additional compounds as H2-receptor histamine antagonists. As a result, a very wide range of chemical structures now exists for this class of drug (for a review, see Cooper et al. [19]). Many of these compounds have been investigated in human studies, but only the above-mentioned five drugs - cimetidine, ranitidine, nizatidine, famotidine, and roxatidine - are marketed as medicines. 

H2-Blockers (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers (p. 172). Cimetidine may lead to drug interactions because it inhibits hepatic cytochrome oxidases. The successor drugs (e.g., ranitidine) are of less concern in this respect. 

CH3NHCNHCH2CH2SCH2 Figure 6.16. Structure of cimetidine, a drug for ulcer treatment. 

A widely prescribed drug for the treatment of gastric ulcers with the generic name cimetidine is a synthetic imidazole derivative Firefly luciferm is a thiazole derivative that IS the naturally occurring light emitting substance present m fireflies... 

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

The Hj-receptor blockers include cimetidine, famotidine, and ranitidine. These drugs are used to decrease gastric acid secretion in the treatment of peptic ulcer, gastroesophageal reflux disorder, and hypersecretory conditions, such as Zollinger-ElUson syndrome. The pharmacodynamics and clinical uses of these drugs are discussed in Chapter 40. 

Certain drugs can reduce the ability of the liver to clear benzodiazepines from the body. These include ulcer drugs, such as cimetidine (Tagamet), birth control pills, propranolol (used to treat hypertension, heart disorders, and migraines), and disulfuram (Antabuse), which is used for the treatment of alcoholism. 

Cimetidine (Tagamet, 8.26), a histamine H2-receptor antagonist for ulcer and heartburn treatment, inhibits several isoforms of CYP CYP1A2, CYP2D6, and, most importantly, CYP3 A4 (Figure 8.5). If a patient takes cimetidine as well as a drug that is metabolized... 

Cimetidine closely resembled metiamide but did not exhibit the granulocytopenia side effect. It was marketed as Tagamet at the end of 1976, as the pioneer drug which revolutionized the medical treatment of peptic ulcer disease [4]. Indeed, in many countries it became the best-selling prescription medicine and was the first of the block-busler products (billion dollar annual sales). 

Chromolyn sodium, an adjunct in the treatment of asthma, acts to inhibit the release of histamine from mast cells. Cimetidine is a drug that resembles histamine in structure. It competes with histamine for receptors in the stomach, and is useful for reducing gastric acid secretion in the treatment of peptic ulcers. 

Cimetidine is indicated for the treatment of disorders associated with hypersecretion of gastric acid, for example, gastric and duodenal ulcer disease, gastroesophageal reflux. The drug competitively antagonizes the H-2 receptor of the parietal cells. 

Cimetidine is a drug used for the treatment of ulcers. The structure includes an imidazole ring (Fig. 6.16) that can be protonated and removed by cation exchange. The method uses a weak cation-exchange sorbent (COOH) for the isolation. 

Patients on long-term warfarin should have an oral anticoagulant treatment booklet. Warfarin has many interactions with commonly prescribed drugs. For example, its effects are enhanced by ibuprofen (analgesic), ketoconazole (antifungal) and cimetidine (used to treat stomach ulcers) and reduced by phenytoin (antiepileptic) and alcohol. 

The imidazole ring is a component of cimetidine, a drug used in the treatment of stomach ulcers. The structure of cimetidine is shown below ... 

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