Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Apr 2008
Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief.
The pharmacokinetics and pharmacodynamics of morphine are under the control of several polymorphic genes, which can account for part of the observed interindividual variation in pain relief. We focused on two such genes: ABCB1/MDR1, a major determinant of morphine bioavailability, and OPRM1, which encodes for the mu-opioid receptor, the primary site of action for morphine. ⋯ Combining the extreme genotypes of both genes, the association between patient polymorphism and pain relief improved (P<0.00001), allowing the detection of three groups: strong responders, responders, and non-responders, with sensitivity close to 100% and specificity more than 70%. This study provides a good example of the possible clinical use of pharmacogenetics.
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Clin. Pharmacol. Ther. · Apr 2008
Differential opioid action on sensory and affective cerebral pain processing.
Low doses of morphine, the most commonly used opioid analgesic, have been shown to significantly reduce the affective but not the sensory intensive dimension of pain. This suggests differential dose-response relationships of opioid analgesia on the sensory and affective components of pain. ⋯ In brain regions associated with the processing of the sensory intensity of pain (primary and secondary somatosensory cortices, posterior insular cortex), activation decreased linearly in relation to alfentanil concentrations, which was significantly less pronounced in OPRM1 118G carriers. In contrast, in brain regions known to process the affective dimension of pain (parahippocampal gyrus, amygdala, anterior insula), pain-related activation disappeared at the lowest alfentanil dose, without genotype differences.
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Clin. Pharmacol. Ther. · Apr 2008
ReviewAnticipating clinical integration of pharmacogenetic treatment strategies for addiction: are primary care physicians ready?
Emerging pharmacogenomics research on addiction to nicotine, alcohol, cocaine, and opiates may soon lead to improved clinical outcomes by tailoring the type, dose and duration of treatment to individual patients' genotypes. To realize the potential of pharmacogenomics in reducing the burden of addiction, several challenges related to clinical integration of novel treatment strategies will need to be addressed concomitantly with ongoing empirical research. These challenges include the preparedness of primary care physicians (PCPs) to incorporate pharmacogenetics into clinical practice, patients' willingness to undergo genetic testing, the resources and infrastructure needed to deliver such services, adequate financing and reimbursement of pharmacogenetic testing, and privacy and antidiscrimination protections sufficient to reassure physicians and patients that genetic testing will not lead to stigmatization and discrimination.