Clinical pharmacology and therapeutics
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The mechanism of the analgesic action of acetaminophen involves the serotonergic system. This study explores how acetaminophen interferes with serotonergic descending pain pathways. Eighteen rapid metabolizers of tropisetron were included in this double-blind cross-over study. ⋯ After CPT, AUC (%*min) of Ap (1,561+/-429) was larger than before CPT (393+/-382, P<0.05); these effects were totally inhibited by tropisetron. Acetaminophen reinforces descending inhibitory pain pathways; it suggests a supraspinal target for acetaminophen's antinociceptive action. This study also confirmed that there is a central serotonergic mechanism of action for acetaminophen that is not stimulus-dependent.
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Clin. Pharmacol. Ther. · Jul 2008
ReviewA continuum for using placebo interventions in regional anesthesia and analgesia studies.
The anesthesiologist Henry K. Beecher is commonly associated with his crusade for informed consent for research. Less recognized is his contribution to the development of principles of randomized controlled trials through his emphasis on surgery as placebo to minimize bias. This article reviews Beecher's contribution and how it should be applied to modern studies of perioperative analgesia.
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Clin. Pharmacol. Ther. · Jul 2008
ReviewInhaled anesthesia: the original closed-loop drug administration paradigm.
We administer anesthetics to obtain therapeutic effects and minimize untoward side effects. Anesthetists can precisely control inhaled anesthetic concentrations by controlling end-tidal volatile anesthetic concentrations. ⋯ The low solubility of modern inhaled anesthetics adds to the stability and control of the anesthetic state; the effective inhaled concentration varies little during maintenance of anesthesia unless altered by the anesthetist. A less precise closed-loop system applies a processed electroencephalogram (EEG) to assess depth of anesthesia and enable accurate delivery of volatile and intravenous anesthetics to maintain a stable state of anesthesia.
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In 1947, a second power of anesthesia was described: "With anesthetic agents we seem to have a tool for producing and holding at will, and at little risk, different levels of consciousness--a tool that promises to be of great help in studies of mental phenomena." In 1995, anesthetic manipulation was coupled with neuroimaging, paving the way for detailed assessments of the relationship between the structure and the functioning of the brain. Anesthesia combined with neuroimaging thus provides a unique tool for investigating the neural correlates of human cognition.
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Clin. Pharmacol. Ther. · Jul 2008
Comparative StudyExposure-response analysis for spontaneously reported dizziness in pregabalin-treated patient with generalized anxiety disorder.
To describe the pregabalin exposure-adverse event (AE) (dizziness) relationship in patients with generalized anxiety disorder, separate models were developed for the incidence of AE and for the conditional severity of AE, given that an AE has occurred using patient data from six clinical studies. The incidence component was modeled using a nonlinear logistic regression model. ⋯ The proportional odds model including a time course of appearance and disappearance of AE could adequately describe the time course of probability of dizziness. Incorporating a transition model including Markov elements improved the model fit and greatly improved the predictability of the time course of probability of dizziness.