Expert opinion on investigational drugs
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Expert Opin Investig Drugs · May 2005
ReviewEvolution of treatments for patients with acute lung injury.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are acute life-threatening forms of hypoxemic respiratory failure. ALI/ARDS patients require intensive care with prolonged mechanical ventilation. Despite advances in our understanding of the pathophysiology of ALI/ARDS, mortality rates remain > 30% and survivors suffer significant decrements in their quality of life. ⋯ Despite previous therapeutic failures, newer surfactant formulations have shown promise, particularly in patients with direct forms of lung injury, and are currently in Phase III trials. Anticoagulant therapy with activated protein C has been shown to improve survival in sepsis, the most common risk factor for the development of ALI/ARDS, and is now being studied in ALI/ARDS. Until new data emerge, the focus must remain on supportive care, including optimised mechanical ventilation, nutritional support, manipulation of fluid balance and prevention of intervening medical complications.
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Alvimopan is a synthetic peripherally restricted mu-receptor opioid antagonist. Alvimopan has a greater affinity for the mu-receptor than the kappa- or sigma-opioid receptors (Ki = 0.77 nM). The polarity of the molecule limits gastrointestinal absorption and central nervous system penetration. ⋯ Adverse events with all doses have been similar to placebo groups. Further efficacy in alleviating opioid-induced bowel dysfunction in patients with chronic opioid usage has also been demonstrated. This evidence-based review assesses this new drug and discusses its potential role in clinical practice.
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Expert Opin Investig Drugs · Nov 2004
A neuroprotective derivative of erythropoietin that is not erythropoietic.
In addition to its well-known erythropoetic effect, erythropoietin (EPO) has also been shown to be neuroprotective in various animal models. In contrast to EPO, carbamylated EPO (CEPO) does not bind to the EPO receptor on UT7 cells or have any haematopoietic/proliferative activity on these cells. In vivo studies in mice and rats showed that even high doses of CEPO for long periods are not erythropoietic. ⋯ Like EPO, CEPO is neuroprotective in a wide range of animal models of neurotoxicity: middle cerebral artery occlusion model of ischaemic stroke, sciatic nerve compression, spinal cord depression, experimental autoimmune encephalomyelitis and peripheral diabetic neuropathy. To date, EPO and CEPO have been exciting developments in the quest for the treatment of various types of neurotoxicity. The development of CEPO should continue.
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Expert Opin Investig Drugs · Oct 2004
ReviewRecent advances in the development of multifactorial therapies for the treatment of traumatic brain injury.
Traumatic brain injury (TBI) is one of the leading causes of death and disability in the industrialised world and remains a major health problem with serious socioeconomic consequences. So far, despite encouraging preclinical results, almost all neuroprotection trials have failed to show any significant efficacy in the treatment of clinical TBI. This may be due, in part, to the fact that most of the therapies investigated have targeted an individual injury factor. ⋯ Accordingly, a successful TBI treatment may have to simultaneously attenuate many injury factors. Recent efforts in experimental TBI have, therefore, focused on the development of neuropharmacotherapies that target multiple injury factors and thus improve the likelihood of a successful outcome. This review will focus on three such novel compounds that are currently being assessed in clinical trials; progesterone, dexanabinol and dexamethasone, and provide an update on the progress of both magnesium and cyclosporin A.
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Expert Opin Investig Drugs · Oct 2004
ReviewThe therapeutic potential of Na+ and Ca2+ channel blockers in pain management.
Chronic pain affects a large percentage of the population, representing a socio-economic burden. Current treatments are characterised by suboptimal efficacy and/or side effects that limit their use. Among several approaches to treating chronic pain, voltage-sensitive Ca(2+) and Na(+) channels are promising targets. This review evaluates the preclinical evidence that supports the involvement of these targets, with specific attention to those subtypes that appear more strictly correlated with pain generation and sustainment, as well as those compounds that modulate the activity of Ca(2+) and/or Na(+) channels that are currently in clinical development for chronic pain conditions.