Current opinion in pharmacology
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Gabapentin and pregabalin are structurally related compounds with recognized efficacy in the treatment of both epilepsy and neuropathic pain. The pharmacological mechanisms by which these agents exert their clinical effects have, until recently, remained unclear. The interaction of gabapentin and pregabalin with conventional antiepileptic and analgesic drug targets is likely to be modest, at best, and has been largely dismissed in favour of a selective inhibitory effect on voltage-gated calcium channels containing the alpha2delta-1 subunit. This mechanism is consistently observed in both rodent- and human-based experimental paradigms and may be sufficiently robust to account for much of the clinical activity of these compounds.
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Curr Opin Pharmacol · Dec 2005
ReviewProbiotics and nutraceuticals: non-medicinal treatments of gastrointestinal diseases.
The demonstration that immune and epithelial cells can discriminate between different microbial and bioactive plant species has extended the known mechanism(s) of action of nutraceuticals and probiotics beyond simple nutrition and/or antimicrobial effects. The progressive unravelling of these plant and bacterial effects on systemic immune and intestinal epithelial cell function has led to new credence for the use of probiotics and nutraceuticals in clinical medicine. Level I evidence now exists for the therapeutic use of probiotics in infectious diarrhea in children, recurrent Clostridium difficile-induced infections and post-operative pouchitis. ⋯ Not all individual probiotic strains have the same efficacy, and future clinical trials may focus on multistrain preparations agents with known efficacy. The use of nutraceuticals and probiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into clinical usage. Scientific studies are providing mechanisms of action to explain the therapeutic effects, and randomized controlled trials are providing the necessary evidence for their incorporation into the therapeutic armamentarium.
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Status epilepticus is a neurological emergency requiring prompt pharmacological intervention. Recent advances in the treatment of this condition include the introduction of treatment algorithms that are tailored more specifically to clinical situations, a trend towards more aggressive therapies if initial treatment with front-line agents fail, and a better understanding of the role of treatment for patients in status epilepticus in the out-of-hospital setting.
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Neuromuscular blocking drugs were introduced into clinical practice in 1942. Although these drugs made new surgical techniques possible, they also led to morbidity and mortality owing to respiratory muscle paralysis and paralysis in the face of inadequate anesthesia. ⋯ Rapid titratable offset of action has been more difficult to achieve, but has been attempted with the inclusion of ester bonds (mivacurium) and binding agents that are in clinical trials. These novel approaches to pharmaceuticals, along with improved understanding of the physiology of the neuromuscular junction in health and disease, have made surgical treatment possible in a wide breadth of clinical situations.
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The long-term use of cannabis, particularly at high intake levels, is associated with several adverse psychosocial features, including lower educational achievement and, in some instances, psychiatric illness. There is little evidence, however, that long-term cannabis use causes permanent cognitive impairment, nor is there is any clear cause and effect relationship to explain the psychosocial associations. There are some physical health risks, particularly the possibility of damage to the airways in cannabis smokers. Overall, by comparison with other drugs used mainly for 'recreational' purposes, cannabis could be rated to be a relatively safe drug.