European journal of clinical pharmacology
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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. · Dec 2008
Clinical TrialCYP2D6 is a major determinant of metoprolol disposition and effects in hospitalized Russian patients treated for acute myocardial infarction.
To investigate individual metabolism-related determinants of metoprolol disposition and effects in patients receiving the drug as standard treatment for acute myocardial infarction (AMI). ⋯ Metoprolol disposition and effects are mainly controlled by CYP2D6 genotype. Patients with gene duplication are at high risk of not benefiting from treatment due to lower metoprolol concentrations. Higher CYP2D6 activity seems to be associated with VRDs complicating AMI, being a negative prognostic factor for patients' survival.
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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.
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Esterases are enzymes of drug metabolism known to be reduced in frail older people and during acute illness. The mechanism for this is unknown. The aim of this study was to examine esterase activity and inflammation in ageing and frailty. ⋯ Frailty was associated with higher inflammatory markers and lower esterase activity. There was a weak but significant negative correlation between both IL-6 and TNF-alpha and the activity of three of four esterases. The negative correlation between esterase activity and inflammatory markers may have a causal basis, comparable to the inflammatory suppression of cytochrome P-450 enzymes.