Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propofol, the recently marketed intravenous induction agent for anaesthesia, is chemically unrelated to earlier anaesthetic drugs. This highly lipophilic agent has a fast onset and short, predictable duration of action due to its rapid penetration of the blood-brain barrier and distribution to the CNS, followed by redistribution to inactive tissue depots such as muscle and fat. On the basis of pharmacokinetic-pharmacodynamic modelling, a mean blood-brain equilibration half-life of only 2.9 minutes has been calculated. In most studies, the blood concentration curve of propofol has been best fitted to a 3-compartment open model, although in some patients only 2 exponential phases can be defined. The first exponential phase half-life of 2 to 3 minutes mirrors the rapid onset of action, the second (34 to 56 minutes) that of the high metabolic clearance, whereas the long third exponential phase half-life of 184 to 480 minutes describes the slow elimination of a small proportion of the drug remaining in poorly perfused tissues. Thus, after both a single intravenous injection and a continuous intravenous infusion, the blood concentrations rapidly decrease below those necessary to maintain sleep (around 1 mg/L), based on both the rapid distribution, redistribution and metabolism during the first and second exponential phases (more than 70% of the drug is eliminated during these 2 phases). During long term intravenous infusions cumulative drug concentrations and effects might be expected, but even then the recovery times do not appear to be much delayed. The liver is probably the main eliminating organ, and renal clearance appears to play little part in the total clearance of propofol. On the other hand, because the total body clearance may exceed liver blood flow, an extrahepatic metabolism or extrarenal elimination (e.g. via the lungs) has been suggested. Approximately 60% of a radiolabelled dose of propofol is excreted in the urine as 1- and 4-glucuronide and 4-sulphate conjugates of 2.6-diisopropyl 1,4-quinol, and the remainder consists of the propofol glucuronide. Thus for hepatic and renal diseases, co-medication, surgical procedure, gender and obesity do not appear to cause clinically significant changes in the pharmacokinetic profile of propofol, but the decrease in the clearance value in the elderly might produce higher concentrations during a long term infusion, with an increased drug effect. In addition, the lower induction dose observed in relation to increased age might be partly explained by a smaller central volume of distribution.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetic implications for the clinical use of propofol. 268 71

Total intravenous anaesthesia (TIVA) with short-acting drugs is a standard procedure for day case surgery and is increasingly used for neurosurgical, cardiac surgical and paediatric surgical operations. The combination of propofol with alfentanil or remifentanil is frequently applied due to its favourable pharmacological properties. Propofol is characterized by a large volume of distribution at steady state and a relatively long elimination half time (t1/2 beta). Because of a high metabolic clearance, the clinical effects of propofol decline rapidly even after prolonged intravenous drug infusion. In patients with increased age, obesity or liver or renal failure, decreased doses of propofol for induction of anaesthesia are recommended. The short-acting opioids alfentanil and remifentanil provide small volumes of distribution at steady state, a short blood-brain equilibration time and decreased t1/2 beta. Remifentanil has unique pharmacological properties due to an ester binding and its elimination via extrahepatic hydrolysis by non-specific blood and tissue esterases. The context sensitive half time of remifentanil is significantly shorter than that of other opioids. Its analgetic potency is equal to fentanyl and 20 to 30 times higher than alfentanil. The advantages of total intravenous anaesthesia include fewer haemodynamic side-effects, a decreased incidence of postoperative nausea and vomiting and less neurohumoral stress response to surgery. Adequate pain therapy is mandatory after total intravenous anaesthesia with short-acting drugs. Continuous infusion of remifentanil for postoperative analgesia or supplementation of regional anaesthesia requires careful monitoring of vital functions. The economic aspects of TIVA remain to be determined.
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PMID:[Perioperative management with short-acting intravenous anesthetics]. 1119 82

Propofol use may lead to hypotension in trauma patients intubated in the emergency department. In this study, predictors of hypotension were identified. We hypothesized that demographic variables could be associated with hypotension. Hypotension occurred in 33 of 200 patients. In the multivariate analysis, hypotension was associated with patient age greater than 55 years (odds ratios [OR], 3.61; 95% confidence interval [CI], 1.32-9.86; P = .012), obesity (OR, 2.66; 95% CI, 1.08-6.55; P = .034), and lower baseline blood pressure (OR, 1.59 [per 10-mm Hg decrease]; 95% CI, 1.29-1.96; P = .000). Age greater than 55 years, obesity, and lower baseline systolic blood pressure are associated with a higher risk of propofol-induced hypotension in trauma patients.
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PMID:Predictors of hypotension associated with propofol in trauma patients. 2439 12