Novel therapeutic approaches to gastric and duodenal ulcers: an update.

Over the last 25 years, a remarkable revolution in the pathophysiology and treatment of gastric and duodenal ulcers has occurred. Effective therapies were developed not only to heal ulcers, but also to cure most patients. The two principal causes for gastric and duodenal ulcers are either infection with Helicobacter pylori or the use of non-steroidal anti-inflammatory drugs (NSAIDs). With H. pylori eradication, gastric and duodenal ulcers are rapidly becoming historical diseases. This communication reviews the salient pharmacology of the novel anti-ulcer drugs currently in development, with particular emphasis on the treatment of gastric and duodenal ulcers. Intense research is currently focused on the development of proton pump inhibitors primarily for the treatment and prevention of gastroesophageal reflux disease. The older proton pump inhibitors, omeprazole and lansoprazole, are effective in healing gastric and duodenal ulcers. Furthermore, both drugs are effective in eradicating H. pylori when given with various antibiotics. Pantoprazole, rabeprazole and esomeprazole are new proton pump inhibitors, which appear to have comparable therapeutic profiles with omeprazole and lansoprazole. Rebamipide is a new mucosal protective drug, which is effective in healing gastric ulcers. Polaprezinc and nocloprost are also mucosal protective drugs, which are in clinical development. However, none of these three cytoprotective drugs have been evaluated for their efficacy in eradicating H. pylori when given in combination with antibiotics. Likewise, no published literature exists on the use of these drugs for preventing NSAID-induced ulcers. With the rapid eradication of H. pylori currently happening in the developed world, the therapeutic challenge is now directed toward preventing NSAID-associated ulcer. Significant reduction of NSAID-induced ulcers is achieved by using continuous prophylactic anti-ulcer therapy (misoprostol or omeprazole) or by using NSAIDs possessing selective COX-2 inhibitory activity. However, outcome clinical studies are needed to compare the adjuvant anti-ulcer therapies given with COX-1 inhibitors versus the selective COX-2 inhibitors given alone.

Stress ulcer.

Stress ulceration is a recognized cause of morbidity and mortality in the critically ill patient. These superficial lesions occur in both the stomach and duodenum within hours after admission to a critical care unit. Although the pathogenesis of stress ulcer is not well understood, it is now established that a decrease in mucosal pH below 6.5 is essential for the induction of stress ulceration. This drop in mucosal pH can result from high luminal hydrogen ion (H+) concentration, increased permeability of the mucosa for H+, or defective neutralizing ability of the mucosa. Local and systemic factors that modulate mucosal blood flow are also important in the development of stress ulceration. It is estimated that 20% to 30% of patients with stress ulcer develop significant gastrointestinal bleeding that requires blood transfusion. The routine administration of H2-receptor antagonists has become standard practice in most intensive care units to prevent the development of stress ulcer and gastrointestinal bleeding, although in many cases their efficacy is unproven. Antacids are clearly effective and remain the gold standard with which alternative therapies are compared. The best treatment for stress ulceration is identification of the patient at risk and institution of prophylaxis. For patients who bleed from stress ulceration, conservative measures should include aggressive treatment of the underlying medical problem and neutralization of acid.