Clinical pharmacology and therapeutics
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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.
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Clin. Pharmacol. Ther. · Mar 2008
Comparative StudyDisease severity is a major determinant for the pharmacodynamics of propofol in critically ill patients.
As oversedation is still common and significant variability between and within critically ill patients makes empiric dosing difficult, the population pharmacokinetics and pharmacodynamics of propofol upon long-term use are characterized, particularly focused on the varying disease state as determinant of the effect. Twenty-six critically ill patients were evaluated during 0.7-9.5 days (median 1.9 days) using the Ramsay scale and the bispectral index as pharmacodynamic end points. NONMEM V was applied for population pharmacokinetic and pharmacodynamic modeling. ⋯ Deeper levels of sedation were found with an increasing SOFA score. With severe illness, critically ill patients will need downward titration of propofol. In patients with cardiac failure, the propofol dosages should be reduced by 38%.
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Clin. Pharmacol. Ther. · Mar 2008
ReviewThe effect of globalization of drug manufacturing, production, and sourcing and challenges for American drug safety.
Americans benefit from one of the safest drug supplies and one of the highest standards of consumer protection in the world. Over the past decade, though, a general trend toward globalization of the supply chains for finished pharmaceutical products and active pharmaceutical ingredients has created new challenges for the Food and Drug Administration (FDA) in ensuring the safety and quality of the drug supply. ⋯ FDA regulatory oversight resources (e.g., those allocated to inspection and testing of imports) are being challenged to keep up with the explosive growth of imported drugs. (In 2006, the FDA performed inspections at 212 foreign drug firms. This number has remained relatively consistent over the past 6 years, starting at 249 in 2001 and ranging from 190 to 260 on an annual basis.)