Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 2008
Comparative StudyAcetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose.
Acetaminophen protein adducts (APAP adducts) were quantified in 157 adolescents and children presenting at eight pediatric hospitals with the chief complaint of APAP overdose. Two of the patients required liver transplantation, whereas all the others recovered spontaneously. Peak APAP adducts correlated with peak hepatic transaminase values, time-to-treatment with N-acetylcysteine (NAC), and risk determination per the Rumack-Matthews nomogram. ⋯ The mean (+/-SD)k(e) and half-life were 0.486 +/- 0.084 days(-1) and 1.47+/- 0.30 days, respectively, and the C(max) was 1.2 (+/-2.92) nmol/ml serum. The model-derived, predicted adduct value at 48 h (Adduct 48) correlated with adductC(max), adduct T(max), Rumack-Matthews risk determination, peak aspartate aminotransferase (AST), and peak alanine aminotransferase (ALT). The pharmacokinetics and clinical correlates of APAP adducts in pediatric and adolescent patients with APAP overdose support the need for a further examination of the role of APAP adducts as clinically relevant and specific biomarkers of APAP toxicity.
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Clin. Pharmacol. Ther. · Aug 2008
Randomized Controlled TrialDevelopment of procedures for early screening of smoking cessation medications in humans.
Candidate medications for smoking cessation may be screened more efficiently if initial evaluations in humans combine the practical advantages of laboratory studies with the clinical validity of clinical trials, such as by increasing participants' "quit motivation" during brief testing. We manipulated "intrinsic" quit motivation by recruiting smokers who either did intend to quit soon ("treatment seekers," N = 47) or did not ("nonseekers," N = 93), and "extrinsic" quit motivation by providing or not providing reinforcement for abstinence ($12/day). ⋯ Reinforcement had a main effect on abstinence but did not moderate the effects of the nicotine patch or treatment-seeking status. Intrinsic, but not extrinsic, quit motivation of participants may enhance the validity of brief tests of medication efficacy for smoking cessation.
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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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Clin. Pharmacol. Ther. · Jul 2008
ReviewSimulated drug administration: an emerging tool for teaching clinical pharmacology during anesthesiology training.
A thorough understanding of the dose-response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects. Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical anesthesia are administered using standard dosing guidelines, without giving due consideration to their pharmacokinetics and dynamics in guiding their administration. Various studies have found that introducing pharmacokinetics and pharmacodynamics as part of the inputs in clinical anesthesiology could lead to better patient care. ⋯ Clinical pharmacology is one of the most challenging topics to teach in anesthesiology. The development of simulators to illustrate the time course of a drug's disposition and effect provides online visualization of pharmacokinetic-pharmacodynamic information during the clinical use of anesthetics. The aim of this review is to discuss the importance of simulation as a clinical pharmacology teaching tool for trainees in anesthesiology.