Drugs of today
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Upper gastrointestinal (GI) bleeding is a common cause of hospitalization and despite effective endoscopic treatments, it is responsible for a significant societal burden due to the associated morbidity, mortality and financial implications. As it has long been hypothesized that acid suppression may help to improve outcomes of patients with gastroduodenal ulcer bleeding, acid-suppressing agents such as histamine-2 receptor antagonists (H(2)RAs) and intravenous (i.v.) proton pump inhibitors (PPIs) have been the subject of study. However, results for H(2)RAs show little if any improvement in outcomes, which may be explained by their insufficient acid suppression and the existence of rapid drug tolerance. ⋯ Randomized trials and meta-analyses have shown that acute high-dose i.v. PPI administration leads to improvements in patients undergoing endoscopic hemostasis for bleeding gastroduodenal ulcers and who also show high risk for rebleeding. However, the optimum dose, timing of administration and subgroups of patients who will benefit most from such treatment need to be further characterized.
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The concept of neuroprotection is based on the understanding that delayed neuronal damage occurs after ischemia. Each step along the ischemic cascade provides an opportunity for therapeutic intervention. Based on the excellent results obtained in experimental models of ischemia, many clinical trials have been conducted with different neuroprotective drugs. ⋯ However, the mechanisms that underlie the development of ischemic damage are still being discovered, creating new therapeutic possibilities for neuroprotection that might be clinically applicable in the future. This article reviews the mechanisms of ischemic neuronal injury, the mechanism of action of neuroprotective agents, current neuroprotective clinical trials, and probable reasons for the failure of clinical neuroprotection. (c) 2003 Prous Science. All rights reserved.