European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Aug 2010
ReviewPharmacogenetic testing and therapeutic drug monitoring are complementary tools for optimal individualization of drug therapy.
Genetic factors contribute to the phenotype of drug response, but the translation of pharmacogenetic outcomes into drug discovery, drug development or clinical practice has proved to be surprisingly disappointing. Despite significant progress in pharmacogenetic research, only a few drugs, such as cetuximab, dasatinib, maraviroc and trastuzumab, require a pharmacogenetic test before being prescribed. There are several gaps that limit the application of pharmacogenetics based upon the complex nature of the drug response itself. ⋯ Third, the use of a pharmacogenetic test as a standard of care for drug therapy has to overcome significant scientific, economic, commercial, political and educational barriers, among others, in order for clinically useful information to be effectively communicated to practitioners and patients. Meanwhile, the lack of efficacy is in this process is quite as costly as drug toxicity, especially for very expensive drugs, and there is a widespread need for clinically and commercially robust pharmacogenetic testing to be applied. In this complex scenario, therapeutic drug monitoring of parent drugs and/or metabolites, alone or combined with available pharmacogenetic tests, may be an alternative or complementary approach when attempts are made to individualize dosing regimen, maximize drug efficacy and enhance drug safety with certain drugs and populations (e.g. antidepressants in older people).
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Eur. J. Clin. Pharmacol. · Oct 2009
ReviewExacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality?
Nonsteroidal anti-inflammatory drugs (NSAIDs), conventional and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely used medications for the treatment of various inflammatory conditions. There is strong evidence of a possible association between the use of these drugs and the relapse of inflammatory bowel diseases (IBD). ⋯ Further randomized, double-blind, controlled trials should be performed to address this issue, and more in vitro studies to identify the pathways involved are required.
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Eur. J. Clin. Pharmacol. · Sep 2009
ReviewInhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future.
Inhaled corticosteroid (ICS) therapy in combination with long-acting beta-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. ⋯ Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases.
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The opioid class of drugs, a large group, is mainly used for the treatment of acute and chronic persistent pain. All are eliminated from the body via metabolism involving principally CYP3A4 and the highly polymorphic CYP2D6, which markedly affects the drug's function, and by conjugation reactions mainly by UGT2B7. In many cases, the resultant metabolites have the same pharmacological activity as the parent opioid; however in many cases, plasma metabolite concentrations are too low to make a meaningful contribution to the overall clinical effects of the parent drug. ⋯ These are norpethidine, a neurotoxic agent, and nordextropropoxyphene, a cardiotoxic agent. Clinicians need to be aware that many opioids have active metabolites that will become therapeutically important, for example in cases of altered pathology, drug interactions and genetic polymorphisms of drug-metabolizing enzymes. Thus, dose individualisation and the avoidance of adverse effects of opioids due to the accumulation of active metabolites or lack of formation of active metabolites are important considerations when opioids are used.
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Eur. J. Clin. Pharmacol. · Sep 2008
ReviewEfficacy of pregabalin and gabapentin for neuropathic pain in spinal-cord injury: an evidence-based evaluation of the literature.
Spinal-cord injury (SCI) is a leading cause of neuropathic pain (NP). Current pharmaceutical treatments for NP in SCI patients are not effective. Two promising options are gabapentin (GP) and pregabalin (PB). Their predominant mechanism of action is believed to be the inhibition of calcium currents, leading in turn to reduced neurotransmitter release and attenuation of postsynaptic excitability. This could explain much of their efficacy in the treatment of both seizure disorders and pain syndromes. However, evidence for their efficacy in attenuating NP of SCI is still controversial. ⋯ There is a lack of studies comparing GP and PB in treating NP in SCI. This systematic review indicates the possible efficacy of PB and GP in NP of SCI. Recommendations for future research to inform clinical practice should include cost-effectiveness studies and dose-response analysis in order to determine the schema employed and the duration of treatment.