Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Apr 2003
ReviewEmerging trends in the pharmacotherapy of chronic pain.
The pharmacotherapy for pain is dominated by conventional analgesics such as the opioids and the non-steroidal anti-inflammatory drugs. Recent advances in the understanding of the mechanisms of pain in general and chronic pain in particular, opened the field of analgesic therapy to newer pharmacological targets, which are aimed at improved efficacy and enhanced tolerability over conventional antipain treatments. ⋯ These and other compounds that are in advanced phases of development for chronic pain are reviewed in this paper. It is hoped that the decade of pain control and research will lead us to an arsenal of effective and safe analgesics that will conquer the problem of chronic pain.
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Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiendotoxin therapies in patients with Gram-negative sepsis, and therapies to modulate the pro-inflammatory mediators produced in response to infection, such as TNF-alpha, platelet-activating factor and complement. ⋯ Nitric oxide produces the cardiovascular features of sepsis and investigators have looked at both reducing its production and mopping up the excess. Attempts to reduce apoptosis have been a new focus in the treatment of sepsis. There have also been recent developments in supportive care suggesting a role for vasopressin and replacement corticosteroid therapy.
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Expert Opin Investig Drugs · Nov 2002
ReviewTreprostinil therapy for pulmonary artery hypertension.
Pulmonary artery hypertension is a life-threatening disease characterised by a pulmonary vasculopathy and progressive right ventricular failure. Major advances were made with the development of continuous intravenous epoprostenol (Flolan trade mark ) as a treatment modality. ⋯ It is a longer acting subcutaneous prostacyclin analogue that offers an additional mode of therapy for this disease. A discussion of the pharmacology of this prostacyclin analogue as compared to its related compounds, the clinical studies which led to its approval, a review of some additional basic studies and the practical use of this drug in the treatment modalities for precapillary pulmonary artery hypertension in 2002 in light of other available therapies is discussed.
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Obesity accelerates morbidity and mortality and has been described by the World Health Organization (WHO) as an epidemic in many industrialised nations [101,102]. Diet, exercise and lifestyle recommendations have proven to be mostly ineffective in adequately preventing or treating the progression of this public health disease. Existing drug treatment is limited by the scarce number of safe and well-tolerated drugs with proven long-term efficacy in maintaining weight loss. ⋯ Yet, despite that obesity is the single most common nutritional problem in many developed nations and despite the devastating health consequences of this unchecked epidemic, investigational anti-obesity drugs face unique and significant challenges due to past and current experiences with anti-obesity drugs. It is anticipated that new anti-obesity drugs for this serious, multifaceted metabolic disease will become as safe and effective and as medically accepted as the treatment of other metabolic disorders such as hypertension, dyslipidaemia or Type 2 diabetes mellitus. This may be particularly important, given that these metabolic disorders may be largely due to or exacerbated by obesity itself.
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Sepsis and septic shock are a major cause of morbidity and mortality in patients admitted to the intensive care unit. Since the introduction of antibiotic therapy, the mortality associated with sepsis has remained within the 30- 50% range. Sepsis constitutes the systemic response to infection. ⋯ This review will examine clinical trials evaluating several strategies for blocking or attenuating TNF-alpha and IL-1beta activity. This review will also survey the current state of experimental therapies involving IL-10, transforming growth factor-beta, granulocyte colony-stimulating factor and IFN-phi. Finally, newer developments related to less known cytokines such as macrophage migration inhibitory factor and high mobility group 1 protein will be evaluated.