المؤلفون: Harvey Wong, Pekka Talke, Paul A. Garcia, Alana M. Flexman, K. Wayne Riggs, Susana Vacas, Tina Shih

المصدر: Anesthesiology. 120:1118-1125

مصطلحات موضوعية: chemistry.chemical_classification, Plasma clearance, medicine.diagnostic_test, business.industry, Pharmacology, Anesthesiology and Pain Medicine, Pharmacodynamic Study, Enzyme, chemistry, Pharmacokinetics, Pharmacodynamics, Anesthesia, Anesthetic, Medicine, Dexmedetomidine, business, Electrocorticography, medicine.drug

الوصف: Background: Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. Methods: Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer’s Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. Results: A two-compartment model was fit to dexmedetomidine concentration–time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. Conclusion: This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::30eb9dd2474055bc869ab7c9ff89d36fTest
https://doi.org/10.1097/aln.0000000000000141Test

المؤلفون: V Nigrovic, A.M Beaufort, M.C Houwertjes, J.Mkh Wierda, Hans Proost

المساهمون: Faculteit Medische Wetenschappen/UMCG, Nanomedicine & Drug Targeting, Faculty of Science and Engineering, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Center for Liver, Digestive and Metabolic Diseases (CLDM)

المصدر: Anesthesiology, 89(3), 707-714. LIPPINCOTT WILLIAMS & WILKINS

مصطلحات موضوعية: Male, PHARMACOKINETICS, medicine.medical_specialty, POTENTIATION, Swine, medicine.drug_class, onset of action, Neuromuscular Junction, Neuromuscular transmission, Suxamethonium chloride, SUCCINYLCHOLINE, PATIENT, CARBOXYLESTERASES, Mivacurium chloride, Internal medicine, medicine, Animals, Cholinesterases, time course of action, plasma clearance, SPEED, PHARMACOLOGY, neuromuscular blocking agents, Butyrylcholinesterase, Cholinesterase, Tetraisopropylpyrophosphamide, biology, business.industry, Muscle relaxant, Isoquinolines, MUSCLE-RELAXANTS, Effective dose (pharmacology), PANCURONIUM, Mivacurium, Anesthesiology and Pain Medicine, Endocrinology, Neuromuscular Depolarizing Agents, biology.protein, Cholinesterase Inhibitors, Onset of action, business, Neuromuscular Nondepolarizing Agents, ATYPICAL PLASMA CHOLINESTERASE, medicine.drug

الوصف: Background The factors that influence the onset time of submaximal ( Methods Twenty pigs received either suxamethonium or mivacurium. Dose finding (70% block) was done for each pig. The enzymic degradation of the muscle relaxant was randomly inhibited by selective inhibition of plasma cholinesterase activity by tetraisopropyl pyrophosphoramide (10 pigs) or was not inhibited (10 pigs). Plasma cholinesterase activities and the mechanomyographic muscle response after peroneal nerve stimulation (0.1 Hz) were measured. Results Inhibition of plasma cholinesterase activity (by 93% and 89%, respectively) increased the onset time of suxamethonium from a median of 40 s (range, 20-45 s) to 131 s (range, 114-166 s; P = 0.009) and of mivacurium from a median of 52 s (range, 40-59 s) to 105 s (range, 90-125 s; P = 0.009). Inhibition of degradation decreased the effective dose of suxamethonium that resulted in 70% depression of the initial twitch height from 900 microg/kg (range, 400-1,000 microg/kg) to 150 microg/kg (range, 135-150 microg/kg) and of mivacurium from 100 microg/kg (range, 80-150 microg/kg) to 35 microg/kg (range, 20-50 microg/kg). Conclusions Inhibition of the enzymic degradation of suxamethonium and mivacurium increases the onset time of submaximal neuromuscular block. Therefore, pharmacokinetics influence the onset time of submaximal neuromuscular block. These results imply that to obtain an ultrashort onset time, muscle relaxants should be developed that not only have a low affinity for the receptor but also rapidly disappear from plasma.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1602d99f834eec98accebb1e412e718Test
https://doi.org/10.1097/00000542-199809000-00022Test

المصدر: Anesthesiology. 89(3):707-714

مصطلحات موضوعية: PHARMACOKINETICS, POTENTIATION, onset of action, MUSCLE-RELAXANTS, SUCCINYLCHOLINE, PATIENT, PANCURONIUM, CARBOXYLESTERASES, time course of action, plasma clearance, SPEED, PHARMACOLOGY, neuromuscular blocking agents, ATYPICAL PLASMA CHOLINESTERASE

الوصف: Background: The factors that influence the onset time of submaximal (Methods: Twenty pigs received either suxamethonium or mivacurium Dose finding (70% block) was done for each pig. The enzymic degradation of the muscle relaxant was randomly inhibited by selective inhibition of plasma cholinesterase activity by tetraisopropyl pyrophosphoramide (10 pigs) or was not inhibited (10 pigs). Plasma cholinesterase activities and the mechanomyographic muscle response after peroneal nerve stimulation (0.1 Hz) were measured.Results: Inhibition of plasma cholinesterase activity (by 93% and 89%, respectively) increased the onset time of suxamethonium from a median of 40 s (range, 20-45 s) to 131 s (range, 114-166 s; P = 0.009) and of mivacurium from a median of 52 s (range, 40-59 s) to 105 s (range, 90-125 s; P = 0.009). Inhibition of degradation decreased the effective dose of suxamethonium that resulted in 70% depression of the initial twitch height from 900 mu g/kg (range, 400-1,000 mu g/kg) to 150 mu g/kg (range, 135-150 mu g/kg) and of mivacurium from 100 mu g/kg (range, 80-150 mu g/kg) to 35 mu g/kg (range, 20-50 mu g/kg).Conclusions: Inhibition of the enzymic degradation of suxamethonium and mivacurium increases the onset time of submaximal neuromuscular block Therefore, pharmacokinetics influence the onset time of submaximal neuromuscular block. These results imply that to obtain an ultrashort onset time, muscle relaxants should be developed that not only have a low affinity for the receptor but also rapidly disappear from plasma.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dris___01423::9eb80ff34c40e4f263d76433a4abc633Test
https://research.rug.nl/en/publications/42f7d70f-543c-4130-9e6a-8057457906a4Test

المؤلفون: Michael B. Howie, G J Suntay, Thomas D. McSweeney

المصدر: Anesthesiology. 77:A363

مصطلحات موضوعية: Plasma clearance, medicine.medical_specialty, Anesthesiology and Pain Medicine, Endocrinology, business.industry, Internal medicine, medicine, Vasodilation, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::8b7b5a7f6f229b309a0a88f481db1e42Test
https://doi.org/10.1097/00000542-199209001-00363Test

المؤلفون: George A. Gregory, Donald R. Stanski, Dennis M. Fisher, Roy Cronnelly, C. O Keeffe, R. D. Miller

المصدر: Anesthesiology. 57(3)

مصطلحات موضوعية: Adult, Aging, Adolescent, Nitrous Oxide, Tubocurarine, Halothane anesthesia, Pharmacology, Anesthesia, General, Models, Biological, Pharmacokinetics, medicine, Paralysis, Humans, Child, Plasma clearance, business.industry, Electromyography, Infant, Newborn, Half-life, Infant, D-Tubocurarine, Kinetics, Anesthesiology and Pain Medicine, Anesthesia, Pharmacodynamics, Child, Preschool, Halothane, medicine.symptom, business, medicine.drug, Half-Life

الوصف: The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n = 9), and adults (12-30 years, n = 8) during 70% nitrous oxide, 0.58 MAC halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained, and the EMG of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurs (Cpss(50)) was 0.18 +/- 0.09 micrograms/ml in neonates, and 0.27 +/- 0.06 micrograms/ml in infants, both significantly lower than the values of 0.42 +/- 0.14 and 0.53 +/- 0.14 micrograms/ml for children and adults, respectively. The steady-state distribution volume (Vdss) was 0.74 +/- 0.33 l/kg in neonates, significantly greater than the values of 0.52 +/- 0.22, 0.41 +/- 0.12, and 0.30 +/- 0.10 l/kg in infants, children, and adults, respectively. The elimination half-life (t beta 1/2) was 174 +/- 60 min in neonates, significantly longer than the values of 90 +/- 23 and 89 +/- 18 min in children and adults, respectively. Plasma clearance did not differ with age. We also determined D50, the product of Vdss and Cpss(50). D50, the quantity of drug present at steady-state to produce 50% paralysis, did not differ between groups. The authors conclude that during comparable nitrous oxide-halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by CPss(50). However, because of the larger Vdss in younger patients, dose size should not differ with age. In addition, because of the longer t beta 1/2 in neonates, second and subsequent doses should be required at less frequent intervals.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3a67275ccf74cc3c75210810997bebaTest
https://pubmed.ncbi.nlm.nih.gov/7114542Test

المؤلفون: F. Chaux, M. Farinotti, C. Salvadori, G. Pandele, P. Duvaldestin

المصدر: Anesthesiology. 59(2)

مصطلحات موضوعية: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Metabolic Clearance Rate, Renal function, Gastroenterology, Pharmacokinetics, Liver Cirrhosis, Alcoholic, Internal medicine, medicine, Humans, In patient, Thiopental, Aged, Volume of distribution, Plasma clearance, business.industry, Blood Proteins, Middle Aged, medicine.disease, Normal group, Kinetics, Anesthesiology and Pain Medicine, Free fraction, Female, business, Half-Life, Protein Binding

الوصف: The effect of cirrhosis on the pharmacokinetics and plasma protein binding of thiopental was studied in eight patients with cirrhosis, aged (mean +/- SD) 42 +/- 11 yr, and nine patients with normal hepatic and renal function, aged 48 +/- 12 yr, undergoing elective abdominal or orthopedic surgery. The total apparent volume of distribution at steady state was of 2.3 +/- 0.5 1 X kg-1 in the controls and of 3.5 +/- 1.9 1 X kg-1 in the patients with cirrhosis. Thiopental plasma clearance based upon total drug concentrations was 3.9 +/- 1.2 ml X min-1 X kg-1 in the normal group and did not differ significantly in the patients with cirrhosis: 4.4 +/- 2.2 ml X min-1 X kg-1. The elimination half-life was of 529 +/- 97 min in the controls and of 714 +/- 252 min in the patients with cirrhosis. The thiopental free fraction was 14.5 +/- 3.4% in the controls and was increased significantly to 25.2 +/- 3.9% in the patients with cirrhosis. Thiopental intrinsic clearance was decreased insignificantly (P = 0.06) from 28.3 +/- 9.0 ml X min-1 X kg-1 in the controls to 18.2 +/- 10.5 ml X min-1 X kg-1 in those with cirrhosis, suggesting that these patients may have a decreased capacity for thiopental metabolism. These results suggest that the risk of a prolonged effect following thiopental administration appears unlikely in patients with cirrhosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f08611e2f7b9d536084a6a7778b8f4fTest
https://pubmed.ncbi.nlm.nih.gov/6869869Test

المؤلفون: C. J. DiFazio, J. C. Moscicki, C. A. DiFazio

المصدر: Anesthesiology. 57:A188-A188

مصطلحات موضوعية: Plasma clearance, Anesthesiology and Pain Medicine, Lidocaine, business.industry, Anesthesia, Medicine, Cimetidine, business, medicine.drug

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::008eec692bec40f06ec113fc3a5ebe4fTest
https://doi.org/10.1097/00000542-198209001-00188Test