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obesity and opioids pharmacokinetics

Frédéric Aubrun, Noël Zahr, Olivier Langeron, Nicolas Boccheciampe, Nathalie Cozic, Lisa Belin, Jean-Sebastien Hulot, Frederic Khiami, Bruno Riou
BACKGROUND: Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics...
February 22, 2018: European Journal of Anaesthesiology
Vidya Chidambaran, Anurag Tewari, Mohamed Mahmoud
PURPOSE: Anesthetic management of obese pediatric patients is challenging. With increasing prevalence of childhood obesity, more severely obese children with comorbidities present for surgery every day. The purpose of this review is to provide an up-to-date comprehensive narrative review on the impact of pathophysiological changes imposed by pediatric obesity on the perioperative management of obese children, especially drug dosing. This knowledge is necessary to provide safe delivery of anesthesia for severely obese children...
March 2018: Journal of Clinical Anesthesia
Nicholas M Dalesio, Craig W Hendrix, Douglas Hale McMichael, Carol B Thompson, Carlton K K Lee, Huy Pho, Rafael S Arias, Rachael Rzasa Lynn, Jeffrey Galinkin, Myron Yaster, Robert H Brown, Alan R Schwartz
BACKGROUND: Obesity causes multiorgan dysfunction, specifically metabolic abnormalities in the liver. Obese patients are opioid-sensitive and have high rates of respiratory complications after surgery. Obesity also has been shown to cause resistance to leptin, an adipose-derived hormone that is key in regulating hunger, metabolism, and respiratory stimulation. We hypothesized that obesity and leptin deficiency impair opioid pharmacokinetics (PK) independently of one another. METHODS: Morphine PK were characterized in C57BL/6J wild-type (WT), diet-induced obese (DIO), and leptin-deficient (ob/ob) mice, and in ob/ob mice given leptin-replacement (LR) therapy...
December 2016: Anesthesia and Analgesia
Magnus Strømmen, Arne Helland, Bård Kulseng, Olav Spigset
OBJECTIVE: Morbidly obese patients on opioid-replacement therapy may be at risk for treatment refusal with regard to bariatric surgery. However, patients on opioid replacement may have the personal skills to facilitate the lifestyle changes required for successful outcomes after bariatric surgery. This planned case observation assessed the effects of sleeve gastrectomy on the pharmacokinetic properties of methadone. METHODS: A white woman in her 40s on methadone maintenance therapy and with morbid obesity was referred for bariatric surgery...
June 2016: Clinical Therapeutics
(no author information available yet)
Weight loss and its long-term maintenance are mainly based on dietary measures and regular physical activity. There are currently no weight-loss medications with a favourable harm-benefit balance. Bupropion is chemically related to certain amphetamines, while naltrexone is an opioid receptor antagonist. A fixed-dose combination of these two drugs has received marketing authorisation in the European Union for obese patients and for over-weight patients with other cardiovascular risk factors. In five placebo-controlled, randomised, double-blind trials, the patients, weighing on average between 100 kg and 105 kg (average body mass index 36 kg/m2), the naltrexone + bupropion combination was associated with an average weight loss of a few additional kilograms compared with placebo, after 6 months or one year of treatment...
October 2015: Prescrire International
Jennifer G Kendrick, Roxane R Carr, Mary H H Ensom
PURPOSE: Clinicians are increasingly likely to have under their care obese children with diseases requiring pharmacotherapy. Optimal drug dosing for this population is unclear. Excess weight likely leads to alterations in pharmacokinetics. The purpose of this article was to describe the pharmacokinetics and pharmacodynamics in overweight and obese children and, where possible, provide recommendations for drug dosing. METHODS: EMBASE (1980-May 2015), MEDLINE (1950-May 2015), and International Pharmaceutical Abstracts (1970-May 2015) databases were searched by using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, pharmacodynamics, drug, dose, drug levels, pediatric, and child...
September 1, 2015: Clinical Therapeutics
Riku Aantaa, Peter Tonner, Giorgio Conti, Dan Longrois, Jean Mantz, Jan P Mulier
BACKGROUND: We offer some perspectives and commentary on the sedation of obese patients in the intensive care unit (ICU). DISCUSSION: Sedation in morbidly obese patients should conform to the same broad principles now current in ICU practice. These include a general presumption against benzodiazepines as first-line agents. Opioids should be avoided in any situation where spontaneous breathing is required. Remifentanil is the preferred agent where continuous stable opioid levels using an infusion are required, because of its lack of context-sensitive accumulation...
2015: Multidisciplinary Respiratory Medicine
David Alexander Sclar
INTRODUCTION: Remifentanil has a rapid onset and short duration of action, predictable pharmacokinetic/pharmacodynamic profile, and unlike fentanyl, does not accumulate with repeated or prolonged administration. This study evaluated predictors of remifentanil use in surgical patients with renal or hepatic impairment, or obesity in the United States who received remifentanil, fentanyl, or the combination. METHODS: Data (2010) from the US Healthcare National Inpatient Database, State Inpatient Database, State Ambulatory Surgery Database, and private hospital and Medicaid databases were used in this analysis...
January 2015: Clinical Drug Investigation
Célia Lloret-Linares, Déborah Hirt, Christophe Bardin, Jean-Luc Bouillot, Jean-Michel Oppert, Christine Poitou, François Chast, Stéphane Mouly, Jean-Michel Scherrmann, Jean-François Bergmann, Xavier Declèves
BACKGROUND AND OBJECTIVES: Obesity and opioid use for chronic pain in obese individuals are both important public health concerns. The pharmacokinetics of oral morphine after Roux-en-Y gastric bypass (RYGB) are unknown. Therefore, we aimed to study the pharmacokinetics of oral morphine in morbidly obese patients before and after RYGB surgery, to identify the effects of RYGB and the subsequent reversal of morbid obesity on the pharmacokinetic parameters of morphine. METHODS: The pharmacokinetics of oral morphine (30 mg) were studied in 30 obese patients before (Visit 1) and then 7-15 days (Visit 2) and 6 months (Visit 3) after RYGB...
October 2014: Clinical Pharmacokinetics
C Lloret-Linares, A Lopes, X Declèves, A Serrie, S Mouly, J-F Bergmann, S Perrot
An increasing number of obese patients are undergoing surgery, particularly bariatric and orthopaedic surgery. The physiological differences between obese and normal-weight subjects may modify not only anaesthetic requirements during surgery but also post-operative analgesic management, raising a number of challenges in a critical period. In this review, we analyse studies of post-operative pain management with opioids in obese subjects. We discuss the genetic factors common to pain and obesity and the factors potentially modifying opioid pharmacokinetics and pharmacodynamics in obese patients, and we analyse the overall efficacy and safety of opioids for pain management during the post-operative period in obese patients...
September 2013: Obesity Surgery
John K Triantafillidis, Emmanuel Merikas, Dimitrios Nikolakis, Apostolos E Papalois
Diagnostic and therapeutic endoscopy can successfully be performed by applying moderate (conscious) sedation. Moderate sedation, using midazolam and an opioid, is the standard method of sedation, although propofol is increasingly being used in many countries because the satisfaction of endoscopists with propofol sedation is greater compared with their satisfaction with conventional sedation. Moreover, the use of propofol is currently preferred for the endoscopic sedation of patients with advanced liver disease due to its short biologic half-life and, consequently, its low risk of inducing hepatic encephalopathy...
January 28, 2013: World Journal of Gastroenterology: WJG
H Ziauddeen, S R Chamberlain, P J Nathan, A Koch, K Maltby, M Bush, W X Tao, A Napolitano, A L Skeggs, A C Brooke, L Cheke, N S Clayton, I Sadaf Farooqi, S O'Rahilly, D Waterworth, K Song, L Hosking, D B Richards, P C Fletcher, E T Bullmore
The opioid system is implicated in the hedonic and motivational processing of food, and in binge eating, a behaviour strongly linked to obesity. The aim of this study was to evaluate the effects of 4 weeks of treatment with the mu-opioid receptor antagonist GSK1521498 on eating behaviour in binge-eating obese subjects. Adults with body mass index ≥ 30 kg m(-2) and binge eating scale scores ≥ 19 received 1-week single-blind placebo run-in, and were then randomized to 28 days with either 2 mg day(-1) GSK1521498, 5 mg day(-1) GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design...
December 2013: Molecular Psychiatry
Jennifer G Kendrick, Roxane R Carr, Mary H H Ensom
OBJECTIVES: To review pharmacokinetics in obese children and to provide medication dosing recommendations. METHODS: EMBASE, MEDLINE, AND INTERNATIONAL PHARMACEUTICAL ABSTRACTS DATABASES WERE SEARCHED USING THE FOLLOWING TERMS: obesity, morbid obesity, overweight, pharmacokinetics, drug, dose, kidney function test, creatinine, pediatric, and child. RESULTS: We identified 10 studies in which the authors examined drug dosing or pharmacokinetics for obese children...
April 2010: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
Pradeep J Nathan, Barry V O'Neill, Mark A Bush, Annelize Koch, Wenli X Tao, Kay Maltby, Antonella Napolitano, Allison C Brooke, Andrew L Skeggs, Craig S Herman, Andrew L Larkin, Diane M Ignar, Duncan B Richards, Pauline M Williams, Edward T Bullmore
Endogenous opioids and µ-opioid receptors have been linked to hedonic and rewarding aspects of palatable food intake. The authors examined the safety, pharmacokinetic, and pharmacodynamic profile of GSK1521498, a µ-opioid receptor inverse agonist that is being investigated primarily for the treatment of overeating behavior in obesity. In healthy participants, GSK1521498 oral solution and capsule formulations were well tolerated up to a dose of 100 mg. After single doses (10-150 mg), the maximum concentration (C(max)) and area under the curve (AUC) in plasma increased in a dose-proportional manner...
April 2012: Journal of Clinical Pharmacology
Andrzej Daszkiewicz, Mariusz Wyleżoł
BACKGROUND: The number of surgical interventions performed in obese patients has recently been increasing. Anaesthesia in a morbidly obese patient may be difficult, due to many pathophysiologic changes and co-morbidities, together with altered pharmacokinetics and pharmacodynamics of anaesthestic agents. We present a case of multimodal preventive analgesia in a bariatric patient with chronic renal failure. CASE REPORT: A 36-year-old, morbidly obese man (BMI 47.8 kg m-2) was scheduled for a laparoscopic adjustable gastric banding (LAGB)...
October 2010: Anestezjologia Intensywna Terapia
J Ingrande, H J M Lemmens
Anaesthesiologists must be prepared to deal with pharmacokinetic and pharmacodynamic (PD) differences in morbidly obese individuals. As drug administration based on total body weight can result in overdose, weight-based dosing scalars must be considered. Conversely, administration of drugs based on ideal body weight can result in a sub-therapeutic dose. Changes in cardiac output and alterations in body composition affect the distribution of numerous anaesthetic drugs. With the exception of neuromuscular antagonists, lean body weight is the optimal dosing scalar for most drugs used in anaesthesia including opioids and anaesthetic induction agents...
December 2010: British Journal of Anaesthesia
Hendrikus J m Lemmens
PURPOSE OF REVIEW: Morbid obesity alters drug dose requirement and time course of drug response. In addition, morbid obesity's impact on many organ systems decreases the margin of safety of anesthetic drugs. Consequently, incorrect dosing will increase the rate of perioperative complications. In this review, we will discuss factors that affect the pharmacokinetics and pharmacodynamics of anesthetic agents in the obese population, we specify certain dosing scalars, and we relate our current knowledge of obesity's effects on the clinical pharmacology of anesthetic drugs...
August 2010: Current Opinion in Anaesthesiology
Célia Lloret Linares, Aline Hajj, Christine Poitou, Guy Simoneau, Karine Clement, Jean Louis Laplanche, Jean-Pierre Lépine, Jean François Bergmann, Stéphane Mouly, Katell Peoc'h
Morbidly obese patients are at significantly elevated risk of postsurgery complications and merit closer monitoring by health care professionals after bariatric surgery. It is now recognized that genetic factors influence individual patient's response to drug used in anesthesia and analgesia. Among the many drug administered by anesthetists, we focused in this pilot study on morphine, since morphine patient-controlled anesthesia in obese patients undergoing gastric bypass surgery is frequently prescribed. We examined the allelic frequency of three polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in patients with body mass index (BMI) >40...
August 2011: Obesity Surgery
Luca La Colla, Andrea Albertin, Giorgio La Colla, Andrea Porta, Giorgio Aldegheri, Domenico Di Candia, Fausto Gigli
BACKGROUND AND OBJECTIVES: In a previous article, we showed that the pharmacokinetic set of remifentanil used for target-controlled infusion (TCI) might be biased in obese patients because it incorporates flawed equations for the calculation of lean body mass (LBM), which is a covariate of several pharmacokinetic parameters in this set. The objectives of this study were to determine the predictive performance of the original pharmacokinetic set, which incorporates the James equation for LBM calculation, and to determine the predictive performance of the pharmacokinetic set when a new method to calculate LBM was used (the Janmahasatian equations)...
2010: Clinical Pharmacokinetics
Sonia M Astle
Achieving pain control in critically ill patients is a challenging problem for the health care team, which becomes more challenging in morbidly obese patients. Obese patients may experience drug malabsorption and distribution, which may lead to either subtherapeutic or toxic drug levels. To manage pain effectively for the critically ill obese patient, nurses must have an understanding of how obesity alters a patient's physiologic response to injury and illness. In addition, nurses must be knowledgeable about physiologic pain mechanisms, types and manifestations of pain, differing patterns of drug absorption and distribution, pharmacokinetic properties of analgesic medications, and pain management strategies...
September 2009: Critical Care Nursing Clinics of North America
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