Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Jan 2008
ReviewNon-steroidal anti-inflammatory drugs, cyclooxygenase-2 and the bone healing process.
Traditional non-steroidal anti-inflammatory drugs (NSAID) and selective cyclooxygenase-2 (COX-2) inhibitors are widely used in the treatment of pain, including bone fracture pain and orthopaedic post-operative pain. The gastrointestinal and cardiovascular adverse effects of NSAIDs are acknowledged, but their effects on bone are less widely known. Prostaglandins play an important role in the regulation of osteoblast and osteoclast functions, and inhibition of prostaglandin production retards bone formation. ⋯ The limited clinical data also support the assumption that inhibition of COX-2 by non-selective or COX-2-selective NSAIDs delays fracture healing. However, the clinical significance of the effect in various patient groups needs to be carefully assessed and further investigations are needed to characterize the patients at the highest risk for NSAID-induced delayed fracture healing and its complications. In the meantime, use of NSAIDs in fracture patients should be cautious, keeping in mind the benefits of pain relief and inhibition of ectopic bone formation on one hand, and the risks of non-union and retarded union on the other hand.
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Basic Clin. Pharmacol. Toxicol. · Nov 2007
ReviewTherapeutic potential of endocannabinoid-hydrolysing enzyme inhibitors.
The specific protein target of delta9-tetrahydrocannabinol (delta9-THC), the main active ingredient of Cannabis sativa L., was characterized from rat brain nearly 20 years ago, and several endogenous compounds and proteins comprising the endocannabinoid (eCB) system have since been discovered. It has become evident that the eCB system consists of at least two cannabinoid receptors (i.e. the CB1 and CB2 receptors), in addition to their endogenous ligands (the eCBs) and several enzymes involved in the biosynthesis and catabolism of the eCBs. ⋯ Inhibitors specifically targeting these enzymes could offer novel therapeutic approaches (e.g. for the treatment of pain and movement disorders). This MiniReview summarizes the literature concerning the potential therapeutic potential of FAAH and MGL inhibitors.
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Basic Clin. Pharmacol. Toxicol. · Sep 2007
ReviewAnti-emetic therapy in cancer chemotherapy: current status.
Nausea and vomiting are ranked as the most severe side effects to chemotherapy by cancer patients. Twenty years ago, treatment of nausea and vomiting from chemotherapy only had moderate effect and often unpleasant side effects. The drugs used included dopamine(2)-receptor antagonists and corticosteroids alone or combined. ⋯ Recommendations for some types of chemotherapy-induced emesis such as delayed emesis, is based on a low level of evidence. Furthermore, the majority of clinical trials include highly selected groups of patients not permitting definite conclusions for other and more heterogeneous patient groups. Development of new anti-emetics with other mechanisms of action is awaited with interest.
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Basic Clin. Pharmacol. Toxicol. · Sep 2007
Randomized Controlled TrialEffects of paracetamol combined with dextromethorphan in human experimental muscle and skin pain.
By combining drugs with different mechanisms of action, synergistic effects may be achieved. The aim of the present experimental pain study was to combine paracetamol with dextromethorphan for synergistic effects. Furthermore, the reproducibility of the pain assessment methods was evaluated. ⋯ There were no statistical differences (all P > 0.05) between paracetamol compared to placebo, and between the effect of paracetamol and dextromethorphan compared to placebo. The acute pain models were not sufficiently sensitive to detect an analgesic effect of paracetamol or the combination with dextromethorphan. The selected dose of dextromethorphan was low as the aim was to use commonly used doses, and a higher dose of dextromethorphan is most likely needed to attenuate the selected pain measures.
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Basic Clin. Pharmacol. Toxicol. · Nov 2006
Case ReportsMassive strontium ferrite ingestion without acute toxicity.
Ingestion of strontium ferrite is previously unreported. We document absorption of strontium without acute toxicity. A 22 year-old schizophrenic man was brought to hospital after he was witnessed to pulverize and ingest flexible adhesive magnets, which later were identified as strontium ferrite. ⋯ He remained otherwise asymptomatic and was discharged to a psychiatric unit approximately 3 weeks later. Although clearly absorbed, strontium ferrite does not appear to produce acute toxicity. Delayed, and or chronic toxicity cannot be excluded based on this report.