Drugs
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Endothelial dysfunction and increased arterial stiffness occur early in the pathogenesis of diabetic vasculopathy. They are both powerful independent predictors of cardiovascular risk. Advances in non-invasive methodologies have led to widespread clinical investigation of these abnormalities in diabetes mellitus, generating a wealth of new knowledge concerning the mechanisms of vascular dysfunction, risk factor associations and potential treatment targets. ⋯ Combination therapy may potentially increase therapeutic efficacy and permit use of lower doses, thereby reducing the risk of adverse drug effects and interactions. Concomitant treatments that specifically target oxidative stress may also improve endothelial dysfunction in diabetes. Vascular function studies can be used to explore the therapeutic potential and mechanisms of action of new and established interventions, and provide useful surrogate measures for cardiovascular endpoints in clinical trials.
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Four weeks' therapy with clopidogrel, in addition to aspirin (acetylsalicylic acid), is currently standard care after percutaneous coronary intervention (PCI) with stent implantation. The recent availability of drug-eluting stents (DES), which dramatically reduce restenosis at the site of PCI, has again raised the issue of stent thrombosis. In clinical trials, the risk of stent thrombosis appeared unrelated to the presence of the drug eluting from the stent and was documented within the usual range of < or =1% at 9 months after DES implantation. ⋯ In such setting, a 12-month aspirin plus clopidogrel regimen showed a beneficial effect on long-term adverse events. An additional consideration is that, among patients undergoing bare-metal stent PCI, combined antithrombotic therapy with aspirin and clopidogrel has been recently associated with favourable effects on cardiovascular outcome beyond stent thrombosis in two large-scale clinical trials. Therefore, we propose that prolonged combination therapy with aspirin and clopidogrel be mandatory up to 1 year after PCI in all patients receiving DES.
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Interest in the use of regional anaesthesia, particularly peripheral nerve blocks (PNBs) and continuous PNBs, has increased in recent years. Accompanying this resurgence in interest has been the development of new local anaesthetics and additives designed to enhance block duration and quality. This manuscript provides a literature-based review on accepted uses of local anaesthetics and adjuncts for a variety of regional anaesthesia techniques. ⋯ Particular emphasis is placed on the long-acting local anaesthetic toxic potential of racemic bupivacaine compared with levobupivacaine and ropivacaine, which are both levorotatory stereoisomers. Guidelines for using ropivacaine and mepivacaine, based on the authors' experience using advanced regional anaesthesia in a busy practice, is provided. Finally, epinephrine (adrenaline), clonidine and other local anaesthetic additives and their rationale for use is covered along with other future possibilities.
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Ropivacaine (Naropin) is the pure S(-)-enantiomer of propivacaine, and is a long-acting amide local anaesthetic agent, eliciting nerve block via reversible inhibition of sodium ion influx in nerve fibres. Ropivacaine is a well tolerated regional anaesthetic effective for surgical anaesthesia as well as the relief of postoperative and labour pain. ⋯ Clinically adequate doses of ropivacaine appear to be associated with a lower incidence or grade of motor block than bupivacaine. Thus ropivacaine, with its efficacy, lower propensity for motor block and reduced potential for CNS toxicity and cardiotoxicity, appears to be an important option for regional anaesthesia and for the management of postoperative and labour pain.
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Subcutaneous recombinant interferon-beta-1a (Rebif) 22 or 44 microg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis (RRMS). It has shown benefits on outcome measures related to relapses, progression of disability and magnetic resonance imaging (MRI) in clinical trials. ⋯ The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-beta-1a 44 microg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS.