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Drug therapy of Peptic Ulker Disease

Drug therapy of Peptic Ulker DiseaseAgents that control acid

  • Antacids neutralize gastric acid within the lumen of the esophagus, stomach, and duodenum. They have been used for many years and are effective in relieving peptic symptoms.
  1. Composition. The magnesium-containing antacids are more potent than those that do not contain magnesium, but they tend to cause diarrhea. Magnesium-free antacids tend to cause constipation. Sometimes the two types are alternated to provide adequate acid control and regulate tolerable bowel habits. Calcium-containing antacids offer the initial acid neutralization and stimulate gastric acid secretion. Another consideration is the sodium content of an antacid when prescribing for a patient who is on a sodium-restricted diet.
  2. Dosage. Most patients take antacids for amelioration of symptoms only. To treat peptic conditions with a full antacid regimen, about 30 mL should be taken 1 and 3 hours after a meal and at bedtime. This regimen requires a daily antacid intake of more than 200 mL, resulting in a monthly cost in excess of $50. Because few patients are likely to adhere to such a program and because of the expense, other medications, described in the following sections, are preferred.
  • H2 antagonists. Histamine is a potent stimulant of gastric acid secretion. For this reason, agents that block the histamine receptor on the parietal cell, so-called H2 antagonists, are effective inhibitors of acid secretion. Interestingly, the H2 antagonists inhibit not only histamine-stimulated acid secretion, but also acid that is stimulated by the vagus nerve (acetylcholine) and by gastrin. This phenomenon suggests an interrelation among these three receptors. The commercially available H2 antagonists are cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid).
  1. Dosage. Typical full therapeutic doses of these agents are cimetidine, 300 mg q.i.d. or 400 mg b.i.d.; ranitidine, 150 mg b.i.d.; famotidine, 20 mg b.i.d. or 40 mg once before bed; and nizatidine, 300 mg once before bed. Alternate regimens also have been used, such as cimetidine, 800 mg at bedtime, and ranitidine, 300 mg at bedtime.
  2. Side effects. The H2 antagonists are remarkably safe, although side effects have been reported. These reports include rare instances of leukopenia and the occasional occurrence of elevated liver enzymes, skin rash, constipation, and diarrhea. Long-term use of cimetidine has been associated with gynecomastia. Ranitidine appears to offer some advantage over cimetidine in that it appears to cause less feminization in men and fewer central nervous system effects, and it has lesser affinity for the cytochrome-P450 system in the liver than does cimetidine, resulting in fewer drug interactions. Both cimetidine and ranitidine interfere with gastric mucosal alcohol dehydrogenase and, if taken before ingestion of alcohol, may increase serum alcohol levels. This effect on alcohol dehydrogenase does not occur with famotidine. Famotidine appears to offer many of the advantages of ranitidine and is slightly longer acting. Nizatidine has a similar profile to ranitidine.
  • Prostaglandins. Prostaglandins are attractive on theoretical grounds because they affect both sides of the mucosal injury-protection balance. They inhibit acid secretion and exert a cytoprotective effect on the mucosa. However, the dose required to elicit the cytoprotective effect is much lower than the acid-inhibitory dose. When prostaglandins are administered in the lower, cytoprotective dose, there is little evidence that they have any clinical benefit.

Drug therapy of Peptic Ulker DiseaseProstaglandin analogs, (e.g., misoprostol (Cytotec)) have been used to treat peptic conditions in clinical trials and appear to be as effective as H2 antagonists in healing ulcers when administered in doses that inhibit acid secretion. However, there is little evidence that synthetic prostaglandins are clinically effective when given in the lower, purely cytoprotective doses that have no effect on acid secretion. Whether the synthetic prostaglandins offer any practical advantages over current therapy is debatable, although one analog that is commercially available, misoprostol, appears to be useful in the prevention and treatment of nonsteroidal antiinflammatory drug-induced gastric ulcers or erosions. Side effects of prostaglandins are diarrhea, and abdominal cramping related to the stimulatory effects of prostaglandins on intestinal smooth muscle and secretion. The contractile effect of prostaglandins on uterine smooth muscle could lead to abortion in pregnant women. For this reason, prostaglandins are not recommended for pregnant women or women of childbearing age who are not using a method of contraception.

  • Proton-pump inhibitors. Currently there are five commercially available proton-pump inhibitors in the United States: omeprazole (Prilosec) and esomeprazole (Nexium), lanzaprazole (Prevacid), rabeprazole (Protonix). Proton-pump inhibitors inhibit gastric acid secretion nearly completely by covalently bonding to the H+-K+-ATPase or the proton pump in the luminal aspect of the cell membrane of the parietal cells. These drugs have been shown to be superior to H2 antagonists healing erosive esophagitis and duodenal and gastric ulcers. Omeprazole was approved by the Food and Drug Administration in 1989, lanzaprazole in 1995, rabeprazole in 1999, pantoprazole in 2000, and esomeprazole sodium in 2001. Only pantoprazole is available in the intravenous formulation in the United States.Proton-pump inhibitors produce faster healing of duodenal ulcers than H2 antagonists, typically healing ulcers in 2 weeks rather than 4 weeks. Proton-pump inhibitors also heal ulcers that were resistant to therapy with H2 antagonists. Similarly, proton-pump inhibitors heal gastric ulcers faster than H2 antagonists and heal gastric ulcers that are resistant to H2 antagonist therapy. Clinical studies have shown that proton-pump inhibitors heal gastric and duodenal ulcers better than H2 antagonists in patients who continue to take nonsteroidal antiinflammatory drugs. Furthermore, proton-pump inhibitors provide better prophylaxis against nonsteroidal antiinflammatory drug damage in the duodenum and stomach than H2 antagonists. All proton-pump inhibitors have been shown to be highly effective as part of an anti-H. Pylori regimen when used along with clarithromycin and either amoxicillin or metronidazole.Proton-pump inhibitors are the drugs of choice for the treatment of patients with the Zollinger-Ellison syndrome. Extensive studies with omeprazole, lanzaprazole, rabeprazole, pantoprazole, and esomeprazole sodium confirmed their efficacy and long-term safety. Because proton-pump inhibitors are safe, have minimal side effects, and heal peptic ulcers faster than H2 blockers, they are the drugs of choice in the treatment of peptic diseases.

Carafate

  • Other drugs. Sucralfate (Carafate) is a substituted disaccharide related to sucrose that appears to act, at least in part, by stimulating endogenous cytoprotection. The drug disperses rapidly in gastric juice of any pH and adheres to tissue protein. In addition to its cytoprotective effects, therefore, sucralfate may temporarily cover ulcers and erosions to help protect them from gastric contents, acid, and pepsin as they heal.Sucralfate (1 g, q.i.d.; or 2 g, b.i.d.) is as effective as H2 antagonists in healing peptic ulcers. It also has been used to treat gastritis associated with nonsteroidal antiinflammatory drugs and erosive esophagitis. The drug may cause constipation but has no serious side effects.Colloidal bismuth subcitrate (De-Nol) and bismuth subsalicylate (Pepto-Bismol) are two bismuth-containing compounds that have enjoyed recent popularity in the treatment of peptic disease. This is largely because of the effectiveness of these agents, sometimes in combination with antibiotics, in the treatment of H. pylori infections of the stomach. Bismuth subsalicylate alone is not effective in healing gastritis or peptic ulcers. Bismuth subcitrate is not available in the United States.

Perspective on drug therapy

Choice of drugs. A wide variety of antiulcer drugs are available to the practitioner. There is little difference in efficacy among treatment regimens using an antacid, an H2 antagonist, a prostaglandin, or sucralfate.

However, proton-pump inhibitors offer advantages in terms of acceleration of healing and is preferred in the treatment of esophageal, gastric and duodenal ulcers as well as refractory peptic ulcer disease and gastric hypersecretory syndromes (e.g., Zollinger-Ellison syndrome). All of the drugs are remarkably safe, and the choice of a drug regimen depends largely on patient or physician preference, cost, and ease of administration. All patients with peptic ulcer disease should be tested for H. pylori either by serologic testing or by endoscopic biopsy techniques and treated for the cure of H. pylori infection.

Long-term treatment. Peptic ulcer disease in most patients is a chronic relapsing condition. Numerous studies have shown that maintenance therapy with a dose of medication that is lower than the dose used to treat acute disease markedly reduces the risk of ulcer recurrence. For example, treatment of patients who have a healed duodenal ulcer with either cimetidine 400 mg at bedtime, ranitidine 150 mg at bedtime, famotidine 20 mg at bedtime, or sucralfate 1 g b.i.d. for 1 year reduces the ulcer recurrence rate to about 25% compared to a 75% recurrence rate in placebo-treated patients.

This experience raises some issues. On one hand, one must consider the costs and risks of the drugs over the long-term; on the other hand, one must also consider the cost and morbidity of ulcer recurrence. In some patients, because of frequent symptoms or complications such as recurrent ulcer bleeding, it is clear that a long-term treatment program is indicated. Other patients have symptoms at predictable times and benefit from therapy that is limited to several weeks to months. Still other patients have such infrequent or mild symptoms that short, intermittent courses of anti-ulcer drugs are sufficient.

In patients who have H. pylori infection and peptic ulceration, eradication of H. pylori has been shown to reduce the recurrence rate of duodenal and gastric ulcers. In patients with recurrent ulcers, H. pylori eradication may result in permanent cure.

Treatment of H. pylori can be accomplished by various regimens including bismuth based or proton-pump inhibitor regimens that include two antibiotics. Since effective treatment requires patient compliance, the simpler regimens are preferred. These oral regimens included a proton-pump inhibitor b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d. or metronidazole 500 mg b.i.d. for 10 to 14 days.

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