Arbaprostil

Abstract: E-type prostaglandins inhibit gastric acid secretion and stimulate gastroduodenal bicarbonate and mucus secretion as well as the formation of hydrophobic surfactant-like phospholipids in the gastric epithelial cells. Furthermore, E-type prostaglandins have trophic effects on the gastro-duodenal mucosa. These effects may partly explain the unique protective effects of E-type prostaglandins against experimental damage of gastroduodenal mucosal lesions in animals and humans. E-type prostaglandins have been used in clinical trials on peptic ulcers, on upper gastrointestinal bleeding, and on mucosal lesions induced by non-steroid anti-inflammatory drugs. In nearly all trials natural prostaglandin E2 as well as the synthetic prostaglandin analogues arbaprostil, misoprostol, enprostil, rioprostil, trimoprostil, and rosaprostol accelerated the healing of peptic ulcers compared with placebo. The PGE analogues must be given in gastric acid antisecretory dosage to reach healing rates similar to those of cimetidine. ...

Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are most frequently used for the treatment of rheumatic disease due to their anti-inflammatory and analgesic properties. All NSAIDs have the potential to cause damage to the gastrointestinal (GI) tract and have been associated with the induction of peptic ulcers and massive life-threatening bleeding. The therapeutic approaches for the treatment and prevention of NSAID-induced ulcers is critically reviewed using data derived from carefully controlled, world-wide clinical studies with anti-ulcer drugs. Histamine (H2) antagonists, omeprazole, sucralfate and E-prostaglandin (PGE) analogs are effective for the treatment of NSAID-induced gastric and duodenal ulcers, if NSAIDs are discontinued. However, if NSAIDs are continued while GI damage is present, the PGE analogs misoprostol, arbaprostil and enprostil have shown efficacy in healing NSAID-induced ulcers. Furthermore, one limited clinical study demonstrated that omeprazole has efficacy in healing NSAID-associated ulcers. Neither H2 antagonists, sucralfate and sulglycotide (a cytoprotective drug) have shown efficacy in preventing NSAID-induced gastric ulcers. However H2 antagonists have shown efficacy in preventing NSAID-induced duodenal ulcers. In contrast, only misoprostol prevents the development of NSAID-induced gastric and duodenal ulcers. Such pharmacological observations suggest that the pathophysiologic mechanisms for the induction of NSAID-induced gastric ulcer are distinctly different from those of NSAID-induced duodenal ulcers. Mild diarrhea and GI intolerance were the predominant adverse reactions experienced by patients receiving synthetic PGEs, particularly enprostil and arbaprostil. From the published data, we conclude that misoprostol is the only anti-ulcer drug proven to be well tolerated and effective for the treatment and prevention of NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAIDs therapy.

Abstract: Oral ketoconazole appreciably reduced the rate of isolation of the outbreak strain from both systemically infected and colonised patients. The outbreak strain did not reappear when ketoconazole was withdrawn. All cases of systemic candidiasis acquired in the unit before April 1984 were caused by the outbreak strain, whereas after May 1984 all cases were caused by other strains. Control of an outbreak depends on its identification and the prevention of cross infection. Existing handwashing reagents can be replaced with fungicidal disinfectants such as Hibisol or Betadine, and antifungal prophylaxis can be given. Recent work in neutropenic patients in whom infection was probably due to an endogenous isolate showed that ketoconazole was as effective as amphotericin B, and prophylaxis with either agent failed.5 In this study ketoconazole failed in six cases, perhaps because of poor absorption in the gut as five patients had undergone major gastrointestinal surgery. Treatment with ketoconazole resulted in the virtual elimination of the outbreak strain, the incidence of cases returning to its former value, with occasional cases caused by the patients' own yeast flora. A much shorter course of prophylaxis might have been equally effective and could be considered in any unit where the incidence of candidal sepsis is unacceptably high and cross infection a problem.