obesity and opioids pharmacokinetics

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...

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...

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...

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...

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...

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)...

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...

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...

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...

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)...

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...

Morphine is an analgesic drug used to treat acute and chronic pain. Obesity is frequently associated with pain of various origins (e.g. arthritis, fibromyalgia, cancer), which increases the need for analgesic drugs. Obesity changes drug pharmacokinetics, and for certain drugs, specific modalities of prescription have been proposed for obese patients. However, scant data are available regarding the pharmacokinetics and pharmacodynamics of morphine in obesity. Prescription of morphine depends on pain relief but the occurrence of respiratory adverse effects correlates with obesity, and is not currently taken into account...

Remifentanil (Ultiva), a fentanyl derivative, is an ultra-short acting, nonspecific esterase-metabolised, selective mu-opioid receptor agonist, with a pharmacodynamic profile typical of opioid analgesic agents. Notably, the esterase linkage in remifentanil results in a unique and favourable pharmacokinetic profile for this class of agent. Adjunctive intravenous remifentanil during general anaesthesia is an effective and generally well tolerated opioid analgesic in a broad spectrum of patients, including adults and paediatric patients, undergoing several types of surgical procedures in both the inpatient and outpatient setting...

BACKGROUND: We previously proposed dosing weights for fentanyl, termed 'pharmacokinetic mass', that span the total body weight (TBW) range from 40 to 210 kg. In this study, we examined the relationships among fentanyl doses needed to achieve postoperative analgesia, corresponding plasma fentanyl concentrations, and pharmacokinetic mass in lean and obese patients undergoing abdominal surgery. METHODS: A total of 69 patients were studied, with TBW ranging from 48 to 181 kg...

The prevalence of obesity has increased 15% up to 20% and represents an important challenge for the anesthesiologist in drug-dosing management. The aim of this work is to provide an overview on physiological changes and pharmacokinetic implications of obesity for the anesthesiologist. Obesity increases both fat and lean masses; however, the percentage of fat tissue increases more than does the lean mass, affecting the apparent volume of distribution of anesthetic drugs according to their lipid solubility. Benzodiazepine loading doses should be adjusted on actual weight, and maintenance doses should be adjusted on ideal body weight...

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The profound segmental antinociception that epidural opioids offer has increased their use over the last 2 decades. Though side effects may accompany the use of epidural opioids, clinicians have found that the advantages far outweigh the disadvantages. The following case report outlines a patient's postoperative course in which she experienced respiratory depression while receiving epidural opioids. The pharmacokinetics of lipophilic vs hydrophilic opioids in relation to the occurrence of respiratory depression is discussed...

OBJECTIVE: To derive recommendations for the dosing of commonly used medications in the morbidly obese patient in the ICU. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: All studies involving the pharmacokinetics or pharmacodynamics of medications in obese subjects or patients. DATA EXTRACTION: The emphasis was on studies involving morbidly obese patients but, in the absence of such data, investigations involving lesser forms of obesity were extracted...

BACKGROUND: Because obesity might affect pharmacokinetic parameters, the authors evaluated the accuracy of target-controlled sufentanil infusion in morbidly obese patients using a pharmacokinetic model usually applied to a normal-weight population. METHODS: Target-controlled propofol and sufentanil coinfusions were administered to 11 morbidly obese patients (body mass index: 45.0 +/- 6.5 kg/m2 ) undergoing laparoscopic gastroplasty. The target plasma propofol concentration was 3 micro g/ml...

Obesity is a worldwide problem, with major health, social and economic implications. The adaptation of drug dosages to obese patients is a subject of concern, particularly for drugs with a narrow therapeutic index. The main factors that affect the tissue distribution of drugs are body composition, regional blood flow and the affinity of the drug for plasma proteins and/or tissue components. Obese people have larger absolute lean body masses as well as fat masses than non-obese individuals of the same age, gender and height...