Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the in vitro effects of increasing concentrations of propofol (5-70 micrograms ml-1), ketamine (10(-6)-10(-3) mol litre-1) and thiopentone (10(-5)-8 x 10(-4) mol litre-1) on the release of preformed histamine and de novo synthesized mediators (peptide leukotriene C4 (LTC4) or prostaglandin D2 (PGD2] from human basophils and mast cells isolated from lung parenchyma and skin tissue and from heart fragments. Propofol, ketamine and thiopentone failed to induce the release of histamine and de novo synthesis of LTC4 from basophils. Propofol induced histamine release from lung (mean 8.6 (SEM 1.6)%) and skin mast cells (3.8 (1.5)%), but not from heart mast cells. Ketamine caused release of histamine from lung (6.2 (0.9)%) and skin mast cells (2.5 (1.5)%). Thiopentone caused a small amount of histamine release from lung mast cells (3.1 (1.2)%). Propofol, ketamine and thiopentone did not induce de novo synthesis of PGD2 and LTC4 from lung and skin mast cells. These results demonstrate that general anaesthetics induce only histamine release selectively from human mast cells.
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PMID:General anaesthetics induce only histamine release selectively from human mast cells. 172 91

The objectives of this study were to assess midazolam and propofol as sedative agents for outpatient gastrointestinal endoscopy, with particular reference to recovery profile, amnesic effects, and haemodynamic state and oxygenation during the procedure. Forty consecutive patients were allocated randomly to two groups. Patients in group I (n = 19) received midazolam 81 (SEM 32) micrograms kg-1; those in group II (n = 21) received propofol 950 (400) micrograms kg-1. Both agents were administered as single injections to similar end-points of sedation. Psychomotor function was assessed using the digit symbol substitution test (DSST). Amnesia was measured with a visual memory test and subjective questionnaire. Patients in group I had a lower DSST score than those in group II (P less than 0.01), indicating a hangover effect from midazolam. Amnesia was similar in the two groups up to the time of removal of the endoscope. More patients in group II remembered removal of the endoscope (P less than 0.001). Oxygen desaturation from baseline was similar in both groups (P less than 0.01). An increase in heart rate and decrease in mean arterial pressure were noted in both groups. Propofol provided more rapid recovery compared with midazolam, but was associated with pain on injection, a short amnesia span, and reduced patient acceptance.
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PMID:Propofol sedation for outpatient upper gastrointestinal endoscopy: comparison with midazolam. 173 54

In 40 patients, the cardiovascular effects of low- and high-dose propofol anesthesia (single bolus of 1.5 mg/kg in group A, 2.5 mg/kg in group C) were examined and compared with those of low- and high-dose thiopental (4 mg/kg in group B, 6.5 mg/kg in group D) (n = 10 patients per group). After induction of anesthesia with etomidate, all patients were ventilated with 70% nitrous oxide in oxygen. Peripheral arterial systolic blood pressure (SAP) and transesophageal echocardiographic short-axis measurements were used to calculate the end-systolic pressure-volume relationship (E) as an index of global myocardial contractility. In all groups SAP decreased significantly below baseline levels for the duration of the measurements (15 min after drug administration), except for the lower dose of thiopental, where SAP returned to baseline values within 10 min. Propofol at a dose of 1.5 mg/kg significantly decreased cardiac output (CO) (from 5.1 +/- 0.25 [mean +/- SEM] to 4.2 +/- 0.23 L/min), stroke volume (SV) (from 64 +/- 3 to 56 +/- 3.6 mL), and the slope of E (from 71 +/- 3.5 to 65 +/- 4.2 mm Hg/mL) until 4 min after drug administration. The higher dose of propofol significantly decreased CO (from 5.1 +/- 0.29 to 4.1 +/- 0.26 L/min), SV (from 64 +/- 3 to 52 +/- 4.6 mL), and the slope of E (from 71 +/- 3.6 to 62 +/- 3.7 mm Hg/mL) until 10 min after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiodynamic effects of propofol in comparison with thiopental: assessment with a transesophageal echocardiographic approach. 173 85

We have studied the effect of i.v. anaesthesia with propofol in the emulsion (Intralipid) formulation on drug distribution and metabolism in six dogs using dual-route administration of propranolol as a model compound. Each dog was studied on two consecutive days: day 1 awake and day 2 during propofol anaesthesia (6 mg kg-1 followed by an infusion of 0.8 mg kg-1 min-1). Propofol anaesthesia was associated with reduced intrinsic clearance by 40% (P less than 0.05) but no significant difference in systemic clearance or hepatic plasma flow. Propofol produced marked changes in drug distribution; volume of distribution (Vss) of propranolol increased 54% from 82.5 (SEM 7.3) litre awake to 127.3 (27) litre during propofol anaesthesia (P less than 0.05). This change was accompanied by an increase (P less than 0.05) in the free fraction of propranolol from 8.5 (0.7) % in awake to 14.0 (0.7) % in propofol-anaesthetized dogs. The combination of the effects of both drug clearance and protein binding resulted in a 65% decrease in the intrinsic clearance of unbound drug (P less than 0.05). In contrast with the effects of propofol on drug distribution, infusion of Intralipid alone in another group of six dogs had no significant effects on drug distribution, protein binding or drug metabolism. We conclude that propofol is a modest inhibitor of drug metabolism, but has major effects on propranolol distribution, possibly by changing plasma protein binding.
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PMID:Effect of i.v. anaesthesia with propofol on drug distribution and metabolism in the dog. 199 61

The effect of pretreatment with fentanyl on the pharmacokinetics of a single bolus of propofol was studied in 17 female patients (mean age 35 yr), ASA grade I. Eight patients received fentanyl 1.5 micrograms kg-1 5 min before induction of anaesthesia. In all patients anaesthesia was induced with propofol 2.5 mg kg-1 and maintained with halothane and nitrous oxide in oxygen. Pretreatment with fentanyl resulted in prolonged apnoea in all eight patients compared with three of nine patients in the control group. The pharmacokinetic values for propofol were described by a three-compartment mammillary model with rapid distribution phases (T1/2 alpha mean (SEM) 3.1 (2.0) min and T1/2 beta 44 (9.1) min) and a slower final phase of T1/2 gamma 520 (96) min. The clearance of propofol was rapid (mean 1.6 (0.24) litre min-1). Propofol was distributed initially into a relatively large central compartment (mean 23.7 (6.6) litre) and was extensively redistributed (mean Vss 593 (157) litre). There was no difference in the pharmacokinetic profile of propofol between the two groups.
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PMID:Pharmacokinetic interaction of propofol and fentanyl: single bolus injection study. 226 45

Propofol, a phenol compound with a short elimination half-life, was compared with thiopental and isoflurane for induction and maintenance of general anesthesia in 60 consenting ASA I, II, and III patients. The study was randomized and open label in design. Hemodynamically, the propofol patients showed a mean +/- SEM decrease in systolic blood pressure in comparison with the thiopental/isoflurane group at 2 (115.1 +/- 4.9 vs. 136.6 +/- 6.0 mmHg), 3 (125.7 +/- 5.1 vs. 149.4 +/- 5.6 mmHg), and 5 min (126.6 +/- 3.8 vs. 144.4 +/- 6.1 mmHg) postinduction and at intubation (135.2 +/- 4.7 vs. 157.8 +/- 6.0 mmHg) (p less than 0.05). The heart rate was lower in the propofol group throughout the induction period (p less than 0.05). Patients who received propofol were ready for discharge from the recovery room sooner (67.9 +/- 4.0 vs. 80.0 +/- 3.6 min) than the thiopental/isoflurane-treated patients (p less than 0.05). Propofol is as safe and effective for induction and maintenance of general anesthesia as thiopental and isoflurane.
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PMID:Comparison of propofol with thiopental and isoflurane for induction and maintenance of general anesthesia. 269 40

Dispersed guinea-pig adrenal cells have been employed in the in vitro estimation of the biological potency and sites of action of drugs acting against the adrenal. The effect of 12 drugs on cortisol secretion from cells stimulated with adrenocorticotrophin (ACTH, 50 ng/L, a 95% saturating dose) has been tested. All the drugs depressed cortisol output in a dose-related fashion. The concentration of drug which inhibited secretion by 50% was (mumol/L, mean +/- SEM): etomidate 0.1 +/- 0.002; epostane 0.44 +/- 0.02: 17-ketotrilostane 0.55 +/- 0.04: trilostane 1.3 +/- 0.1: metyrapone 3.5 +/- 0.6: cyproterone acetate 4.6 +/- 0.2: megestrol acetate 11 +/- 2: danazol 22 +/- 2: aminoglutethimide 41 +/- 5: stanozolol 50 +/- 4: thiopentone 160 +/- 18: propofol 170 +/- 18. The sites of the anti-steroidogenic effect of seven of these drugs have also been established using a method based upon the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of cortisol by adrenal cells. Propofol acts between ACTH binding and pregnenolone production, trilostane, megestrol acetate and cyproterone acetate are 3 beta-hydroxysteroid dehydrogenase inhibitors whereas metyrapone, etomidate and thiopentone act at 11 beta-hydroxylase.
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PMID:On the assessment of the in vitro biopotency and site(s) of action of drugs affecting adrenal steroidogenesis. 302 52

The effects of a bolus injection of propofol on mean intracranial pressure were studied in six adult, comatose patients who had severe head injuries. Propofol 2 mg/kg was given intravenously over 90 seconds when the mean intracranial pressure reached or exceeded 25 mmHg. Arterial blood gas values, heart rate and central venous pressure remained stable at all measurements. Arterial blood pressure decreased statistically significantly (p less than 0.05) within one minute after propofol administration. The mean (SEM) intracranial pressure decreased statistically significantly (p less than 0.05) at 30 seconds and at 1 and 2 minutes, from 25 (3) to 11 (4) mmHg. The cerebral perfusion pressure decreased statistically significantly from 92 (8) mmHg at all measurements (p less than 0.05). The lowest value at 3 minutes was 50 (7) mmHg but in four patients at that time the perfusion pressure was below 50 mmHg.
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PMID:Effect of propofol on elevated intracranial pressure. Preliminary results. 325 86

We have studied the effects of a 30-min infusion of propofol 6, 9, 12, 15, 18 and 21 mg kg-1 h-1 on cardiovascular haemodynamics, coronary circulation and myocardial metabolism in 12 mongrel dogs. Mean plasma concentrations of propofol after infusion of 6 and 21 mg kg-1 h-1 increased from 2.9 (SEM 0.3) to 11.5 (0.1) micrograms ml-1. Propofol produced a progressive decrease in arterial pressure. Heart rate tended to decrease at 15, 18 and 21 mg kg-1 h-1 and cardiac index decreased significantly at infusion rates > or = 9 mg kg-1 h-1. Systemic vascular resistance tended to increase except at 21 mg kg-1 h-1 and left ventricular systolic and diastolic function were depressed. Both coronary sinus blood flow and myocardial oxygen consumption decreased in parallel with a decrease in left ventricular minute work index without producing lactate. Propofol produced progressive decreases in coronary blood flow and myocardial oxygen consumption but did not exert adverse effects on the coronary circulation.
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PMID:Effects of graded infusion rates of propofol on cardiovascular haemodynamics, coronary circulation and myocardial metabolism in dogs. 757 91

Mild intraoperative hypothermia is common. We therefore studied the effects of mild hypothermia on propofol pharmacokinetics, hepatic blood flow, and atracurium duration of action in healthy volunteers. Six young volunteers were studied on two randomly assigned days, at either 34 degrees C or 37 degrees C. Anesthesia was induced with thiopental, 3 mg/kg, and maintained with 70% N2O and 0.6% isoflurane. Core hypothermia was induced by conductive and convective cooling. On the other study day, normothermia was maintained by a Bair Hugger (Augustine Medical, Inc., Eden Prairie, MN) forced-air warmer. Propofol, 1 mg/kg lean body mass (LBM), then was given, followed by a 4-h infusion at 5 mg.kg-1.h-1. After 2 h, atracurium 0.5 mg/kg was administered as an intravenous bolus. Indocyanine green was administered for estimation of hepatic blood flow. Arterial blood was assayed for propofol and indocyanine green concentration. Pharmacokinetic analysis was performed using NONMEM. Results are reported as means +/- SEM. Propofol blood concentrations averaged approximately 28% more at 34 degrees C than at 37 degrees C (P < 0.05). Hepatic blood flow decreased 23% +/- 11% in normothermic volunteers during the propofol infusion, and 33% +/- 11% in hypothermic volunteers (P = not significant). A three-compartment mamillary model fitted the data best. Inclusion of hepatic blood flow change from the prepropofol baseline as a covariate for total body clearance significantly improved the fit. The intercompartmental clearances were decreased in the presence of hypothermia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium. 856 56


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