Treatment of Peptic Ulcers

Bismuth subsahcylate [14882-18-9] Pepto-Bismol, is a basic salt of varying composition, corresponding approximately to i9-H0CgH4C02(Bi0). Like a number of other insoluble bismuth preparations, it is not currentiy approved in the United States for the treatment of peptic ulcer disease but is under active investigation for this purpose (180). It does appear to be effective for the rehef of mild diarrhea and for the prevention of travelers diarrhea (181). The ready availabiUty of this dmg, however, may lead to its ovemse and result in toxic effects caused by both the saUcylate and bismuth components. It has been suggested that bismuth subsahcylate is somewhat effective in the symptomatic treatment of isosporiasis, a disease caused by the intracellular parasite Isospora belli (182). 

Hydroxy-A, A -bis(hydroxymethyl)-A -methylmethanaminium salts and related types of compounds 19 for prevention and treatment of peptic ulcers and... 

A great many organic quaternary bases can inhibit the action of acetyl choline in organ systems activated by that neurotransmitter and thus possess anticholinergic-antispasmodic activity. One such agent is methantheline bromide (4), used in the treatment of peptic ulcer and as an antispasmodic agent in intestinal disorders. Its synthesis Involves Friedel-Crafts cyclization of o-... 

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]. 

EDUCATING THE PATIENT WITH A PEPTIC ULCER The nurse gives the patient with a peptic ulcer a full explanation of Hie treatment regimen, which may include dru and a special diet. The patient is instructed to take the drug exactly as prescribed by file primary health care provider (eg, 30 minutes before meals or between meals) to obtain file desired results. The nurse discusses file importance of diet in file treatment of peptic ulcer and gives a full explanation of file special diet (when ordered). 

Mr. Anthony is prescribed a cholinergic blocking drug for the treatment of peptic ulcer. In planning patient teaching for Mr. A nthony before dismissal from the hospital, determine what information must be included to prevent complications of therapy. 

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. 

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. 

Brunton, L., Agents for control of gastric acidity and treatment of peptic ulcers, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill, New York, 1996, chap. 37. 

The anti-ulcer agents omeprazole, lanzoprazole, and pantoprazole have been introduced during the past decade for the treatment of peptic ulcers. Gastric acid secretion is efficiently reduced by prazole inhibition of H+K+-ATPase in the parietal cells of the gastrointestinal mucosa [75]. The prazoles themselves are not active inhibitors of the enzyme, but are transformed to cyclic sulfenamides in the intracellular acidic compartment of parietal cells [76]. The active inhibitors are permanent cations at pH < 4, with limited possibilities of leaving the parietal cells, and thus are retained and activated at the site of action. In the neutral body compartments the prazoles are stable, and only trace amounts are converted to the active drugs. (For a review on omeprazole, see Ref. [77].)... 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

The goals of medical treatment of peptic ulcer disease are to relieve symptoms, heal the ulcer and to prevent recurrence. For the first two the therapeutic tactics are aimed at reducing aggressive factors, in the first place gastric acid, and to promote or introduce defensive or cytoprotective factors. For... 

Le. Other Drugs for Treatment of Peptic Ulcer Disease... 

Lazzaroni M, Bianchi Porro G. Treatment of peptic ulcer in the elderly. Proton pump inhibitors and histamine H2 receptor antagonists. Drugs Aging 1996 9(4) 251-61. 

SoU AH. Consensus conference. Medical treatment of peptic ulcer disease. Practice guidehnes. Practice Parameters Committee of the American College of Gastroenterology. JAMA 1996 275(8) 622-9. 

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. 

H2 Antagonists and the Treatment of Peptic Ulcers. Treatment of peptic ulcers is a complicated and multilevel therapy in which Hj antagonists are very successful and widely used (and abused). Peptic ulcers may affect either the stomach (gastric ulcers, less common overall but more common in people with iatrogenic [i.e., physician-induced] ulcers from the use of nonsteroidal anti-inflammatory drugs [NSAIDs]) or the duodenum (duodenal ulcers). The lining of the stomach or duodenum is attacked by the digestive juices to such an extent that the protective mucous layer on the surface has... 

G. L. Garay, J. M. Muchowski (1985). Agents for the treatment of peptic ulcer disease. Annu. 

Bismuth compounds have been used in the treatment of peptic ulcer disease. They function by selective binding to the ulcer, coating it and shielding it from the effects of gastric acid. Bismuth may also have activity against bacteria such as Helicobacter pylori, shown to be a causative factor in peptic ulcer disease of the stomach. Bismuth has been administered as bismuth subsalicylate (8.95) or tripotassium dicitrato bismuthate. 

As discussed earlier, receptors are responsible for histamine induced gastric acid secretion. H -receptors antagonists such as cimetidine, ranitidine, famotidine etc. are used in the treatment of peptic ulcer and are discussed in chapter Antiulcer agents. ... 

Starzynska T, Mandat A. 1987. [A case of argyria after peroral treatment of peptic ulcer with silver albuminate], Wiad Lek 40 691-693. (Polish). 

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