Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Sep 2014
Randomized Controlled TrialPharmacokinetic-pharmacodynamic modelling of the analgesic and antihyperalgesic effects of morphine after intravenous infusion in human volunteers.
Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy individuals (15 males). ⋯ The sensitivity covariate was significant on baseline EPTo values and genetics as a covariate on the placebo slope for 2HA. The analgesic and antihyperalgesic effects of morphine were pharmacologically distinct as the models had different effect site equilibration half-lives and different covariate effects. Morphine had negligible effect on 2HA, but significant effect on EPTo.
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Basic Clin. Pharmacol. Toxicol. · Sep 2014
Simplified acute physiology score II/acute physiology and chronic health evaluation II and prediction of the mortality and later development of complications in poisoned patients admitted to intensive care unit.
We aimed to determine the acute physiology and chronic health evaluation (APACHE) II and simplified acute physiology score (SAPS) II in poisoned patients admitted to the poisoning ICU and compare them to see which is a more sensitive and specific system for prognostication of the mortality and complications in these patients. Between February 2013 and July 2013, all patients referring to our centre with any poisoning mandating ICU admission were prospectively included. On ICU arrival, a questionnaire containing the demographic data, parameters of the APACHE II and SAPS II scores, the sum of the scores, complications during the stay and the patients' final outcome (compete recovery versus death) was filled for every single patient. ⋯ APACHE II was a better score in prediction of both mortality and later complications in the setting of poisoning ICU. APACHE >22 has a good specificity in determining the mortality and development of further complications in poisoned patients admitted to the medical toxicology ICUs. SAPS II score >59 and >43 can predict the risk of mortality and later complications in these patients, as well.
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Basic Clin. Pharmacol. Toxicol. · Sep 2014
The association between use of serotonergic antidepressants and perioperative bleeding during total hip arthroplasty--a cohort study.
In vitro studies have shown that selective serotonin reuptake inhibitors inhibit platelet aggregation. It is well documented that SSRIs cause serious gastrointestinal bleeding, but studies on other bleeding manifestations have been equivocal. Our objective was to determine a possible association between use of serotonergic antidepressants (SA) and perioperative bleeding during hip replacements. ⋯ Only 48 subjects (3.6%) had transfusions. Use of SA was associated with an increased blood loss compared with non-users. The hypothesis that SA impairs haemostasis is supported by these results.