Pharmacology and Obesity

Lemmens, Hendrikus J. M.; Ingrande, Jerry

doi:10.1097/aia.0b013e31829a4d56

Cited by 23 publications

(20 citation statements)

References 31 publications

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“…al . recommended that lean body mass (LBM) correlates well with cardiac output and is more suitable for weight based induction of anesthesia with propofol [62-64]. The reasoning was that since cardiac output is a determinant of the initial concentration of propofol after the administration of a short intravenous infusion, as during induction of anesthesia [62], and obesity-related increase in LBM appears to be the main determinant of cardiac output, LBM may be a better scalar for dosing propofol induction doses.…”

Section: ) Propofol Pharmacokinetics (Pk) and Pharmacodynamics (Pd) mentioning

confidence: 99%

Propofol: A Review of its Role in Pediatric Anesthesia and Sedation

2015

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Propofol is an intravenous agent used commonly for induction and maintenance of anesthesia, procedural and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially gamma-aminobutyric acid A receptor. Approved for use in the United States by the Federal Drugs and Administration (FDA) in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exist despite the FDA mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after six hours. While propofol has advantages over inhalation anesthesia like less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.

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Section: ) Propofol Pharmacokinetics (Pk) and Pharmacodynamics (Pd) mentioning

confidence: 99%

Propofol: A Review of its Role in Pediatric Anesthesia and Sedation

2015

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“…For example, maintenance doses are mostly driven by total body clearance (Cl), which is the sum of the clearances by each of the eliminating organs (primarily the liver and kidneys), and increased organ mass in obesity may influence Cl . Increased renal clearance was attributed to increased kidney mass and renal blood flow in obesity, and it may affect the elimination rate (k) . In addition, Cl estimations are influenced by the definition of weight used, with weight‐normalized Cl often correlating better with modified body weights such as LBW instead of TBW …”

Section: Body Mass Index Classificationmentioning

confidence: 99%

“…Changes in antimicrobial pharmacokinetics based on physiologic alterations in noncritically ill and critically ill obese patients . *Additional factors as commonly described in a critically ill population.…”

Section: Body Mass Index Classificationmentioning

confidence: 99%

“…4 Increased renal clearance was attributed to increased kidney mass and renal blood flow in obesity, and it may affect the elimination rate (k). 1,5 In addition, Cl estimations are influenced by the definition of weight used, with weight-normalized Cl often correlating better with modified body weights such as LBW instead of TBW. 5 Elimination half-life (t 1/2 ) is related to Vd and Cl through two equations: k = Cl/Vd and t 1/2 = 0.693/k.…”

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confidence: 99%

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Comprehensive Guidance for Antibiotic Dosing in Obese Adults

et al. 2017

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Physiologic alterations seen in obesity commonly impact the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics and may result in suboptimal dosing in this expanding but understudied population. Much of the published clinical and PK evidence to date consists of small patient populations and are retrospective with, not infrequently, heterogeneous results that in some cases are contradictory. In the last 10 years, additional antimicrobial PK/PD and clinical data encompassing prolonged infusion strategies and examination of critically ill populations have emerged to inform antimicrobial dosing in obesity. In this narrative review, we critically review literature on dosing, PK, and possible dosing strategies in obese adults. We searched PubMed, Scopus, and the Cochrane Library using Medical Subject Headings including anti-infectives, specific antimicrobial names, obese, pharmacokinetics, and others. We reviewed articles, cross-referenced select cited references, and when applicable, referenced drug databases and package inserts to develop dosing recommendations. We provide an overall critical review of the available data regarding PK and dosing issues including dosing recommendations in both critically ill and noncritically ill patients with significant obesity. We developed dosing recommendations for 34 antimicrobials based on 121 articles of the 2336 identified by the search strategy. Although 11 of these do not appear to require dose adjustment, obesity-specific dosing guidance is provided for the remaining 23 antimicrobials. Additional studies are needed to better understand and resolve discrepant published results regarding the PK of antibiotics to establish optimal dosing strategies in obese adults. Alternative dosing strategies, such as extended infusions, should be considered for time-dependent antibiotics (e.g., β-lactams) in obese patients to achieve PD targets reliably. Therapeutic drug monitoring across the spectrum of antimicrobials is of increasing importance in this and other populations to ensure optimized dosing.

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“…3 The appropriate weight scalar for these drugs is the lean-scaled weight. 2 Here we have shown that the blood volume corrected for obesity can be calculated using the product of the lean-scaled weight and the blood volume index.…”

Section: To the Editormentioning

confidence: 99%

Lean-scaled weight can be used to estimate blood volume for obese patients

Friesen

2014

Can J Anesth/J Can Anesth

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Pharmacology and Obesity

Cited by 23 publications

References 31 publications

Propofol: A Review of its Role in Pediatric Anesthesia and Sedation

Propofol: A Review of its Role in Pediatric Anesthesia and Sedation

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

Lean-scaled weight can be used to estimate blood volume for obese patients

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