Current opinion in pharmacology
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In the last decade, the relationship between drug dosing and treatment efficacy for life-threatening fungal infections has been clarified by application of pharmacodynamic principles to the study of antifungal agents. Similar to antibacterials, antifungal agents can display static or cidal patterns of activity against pathogenic fungi that can be broadly classified as either concentration-dependent or concentration-independent. The differences between these pharmacodynamic patterns can play an important role in the selection and dosing of antifungal therapy, especially in the treatment of uncommon or resistant mycoses. Knowledge of these pharmacodynamic characteristics may also guide an exploration of unconventional dosing strategies that could prove to be as effective, safe, and more convenient in critically ill or persistently immunosuppressed patients.
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Curr Opin Pharmacol · Aug 2007
ReviewDevelopments in systemic immunomodulatory therapy for psoriasis.
Psoriasis is an inflammatory skin condition that can be accompanied by joint disease. Pre-biological and biological systemic therapies are effective. Dermatologists have used systemic immunomodulators including methotrexate to treat moderate-to-severe disease for over 30 years. ⋯ Tumor necrosis factor-blockers have controversial associations with certain cancers and infections. Biologics require clinical monitoring and have specific contraindications. Scientists are exploring several new therapeutic targets.
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Curr Opin Pharmacol · Jun 2007
ReviewSelective relaxant binding agents for reversal of neuromuscular blockade.
Traditionally, reversal of neuromuscular blockade during anaesthesia was achieved by increasing the acetylcholine concentration in the neuromuscular junction using acetylcholinesterase inhibitors. However, this is ineffective against profound blockade. Furthermore, the increase in acetylcholine level is not limited to the neuromuscular junction, resulting in unwanted side effects requiring co-treatment with muscarinic antagonists. ⋯ As part of this new approach, cyclodextrin molecules have been designed that selectively encapsulate steroidal neuromuscular blocking agents. Both animal and human experiments have demonstrated that fast, effective and complete recovery from both normal and profound neuromuscular blockade is now possible. Furthermore, these cyclodextrin derivatives do not have the unwanted side effects of acetylcholinesterase inhibitors.
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Infection with Chlamydophila pneumoniae or Mycoplasma pneumoniae has been linked to asthma. There is evidence to suggest that persistent infection with these organisms might lead to an increase in the severity of asthma. beta-Lactam antibiotics have not been shown to be beneficial in the treatment of asthma but several studies have indicated that macrolides and related antibiotics might be useful both for the treatment of chronic asthma and for acute exacerbations. However, these observations need to be confirmed in further studies. It is not clear whether any effect that these antibiotics has is a result of antimicrobial actions against organisms such as C. pneumoniae or whether it is due to their anti-inflammatory action.
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Cardiac failure is characterised by the loss of cardiomyocytes, and several strategies to replace the lost cell mass are being developed. Animal models have demonstrated the therapeutic potential of several cell types, and both autologous skeletal myoblasts and bone marrow progenitor cells have been tested in preliminary clinical trials. However functional improvements have been modest and the mechanism of benefit is unclear, although myocardial regeneration is not a significant factor. Alternative strategies using autologous resident cardiac progenitor cells or embryonic stem cell-derived cardiomyocytes could recreate de novo myocardium with higher efficiency, although various hurdles must be overcome before these strategies are translated to the clinic.