Clinical pharmacology and therapeutics
-
Clin. Pharmacol. Ther. · Feb 2012
Practice GuidelineClinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype.
Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine as an analgesic are governed by CYP2D6 polymorphisms. Codeine has little therapeutic effect in patients who are CYP2D6 poor metabolizers, whereas the risk of morphine toxicity is higher in ultrarapid metabolizers. The purpose of this guideline (periodically updated at http://www.pharmgkb.org) is to provide information relating to the interpretation of CYP2D6 genotype test results to guide the dosing of codeine.
-
Clin. Pharmacol. Ther. · Feb 2012
Rational opioid dosing in the elderly: dose and dosing interval when initiating opioid therapy.
Opioids are the mainstay of treatment for moderate to severe pain. However, opioid therapy in the elderly is often associated with significant morbidity because of excessive ventilatory depression. The large amount of interindividual variability in opioid dose-response relationships makes it difficult to individualize the dose and dosing interval to provide safe and effective analgesia. By examining how aging affects the pharmacokinetics (PK) and pharmacodynamics (PD) of opioids, it is possible to provide a rational basis for age adjustment in opioid dosing.
-
Clin. Pharmacol. Ther. · Feb 2012
Plasma noradrenaline and state anxiety levels predict placebo response in learned immunosuppression.
Large interindividual differences exist in the presence and extent of placebo responses in both experimental and clinical studies, but little is known about possible predictors of these responses. We employed a behaviorally conditioned immunosuppression paradigm in healthy men to analyze predictors of learned placebo responses. During acquisition, the subjects received either the immunosuppressant cyclosporin A (n = 32) or a placebo (n = 14) (unconditioned stimuli (US)) together with a novel-tasting drink (conditioned stimulus (CS)). ⋯ Nonresponders (n = 17) did not show responses different from those of the controls. Multiple-regression analyses showed that baseline IL-2, plasma noradrenaline, and state anxiety predicted nearly 60% of the variance in the conditioned IL-2 response. These data provide first evidence for putative biological and psychological predictors of learned placebo responses.
-
Clin. Pharmacol. Ther. · Feb 2012
ReviewKetamine as a novel antidepressant: from synapse to behavior.
Recent reports of a rapid antidepressant effect of the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, even in treatment-resistant populations, have spurred translational therapeutic and neuroscience research aimed at elucidating ketamine's mechanism of action. This article provides a concise overview of research findings that pertain to the effects of low-dose ketamine at the cellular, neurocircuitry, and behavioral levels and describes an integrated model of the action of ketamine in the treatment of depression.