Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Aug 2010
ReviewDopaminergic and non-dopaminergic pharmacological hypotheses for gait disorders in Parkinson's disease.
Gait disorders form one component of the axial disorders observed in Parkinson's disease (PD). Indeed, short steps with a forward-leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late-stage therapeutics--levodopa and electrical subthalamic nucleus (STN) stimulation. ⋯ Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.
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Fundam Clin Pharmacol · Aug 2010
Case ReportsAcute generalized exanthematous pustulosis (AGEP) induced by cefotaxime.
We report a case of acute generalized exanthematous pustulosis (AGEP) after cefotaxime use confirmed by a positive patch test. A 30-year-old woman received cefotaxime, fosfomycin and ciprofloxacin for sinusitis. Twelve days after drug initiation, she developed an extending pustular erythema associated with fever. ⋯ Patch tests were positive to cefotaxime after 48 h, while ciprofloxacin and fosfomycin yielded negative findings. Based on the Naranjo algorithm, it is probable that AGEP reaction was caused by cefotaxime. To our knowledge, this is the first reported case of AGEP associated with positive cefotaxime patch testing.
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Fundam Clin Pharmacol · Aug 2010
Randomized Controlled TrialThe antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes.
The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P = 0.007). ⋯ The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.
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Fundam Clin Pharmacol · Aug 2010
Effects of induced hyperthermia on pharmacokinetics of ropivacaine in rats.
Ropivacaine is a local anaesthetic used for epidural anaesthesia and postoperative pain relief. Hyperthermia is a very common sign of infection associated with variations in physiological parameters, which may influence drugs pharmacokinetics. The aim of this study was to determine the effects of induced hyperthermia on ropivacaine pharmacokinetics in rats. ⋯ Results suggest a higher tissular distribution of ropivacaine and an increase in blood-brain barrier permeability during hyperthermia. The hyperthermia-induced increase in V(d) could be responsible for an increase in cerebral ropivacaine toxicity. These experimental data provide a basis for future clinical investigations in relation to local anaesthetic use in hyperthermic patients.