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Pharmacokinetics in Obese Patients: Drug Absorption and Distribution01:25

Pharmacokinetics in Obese Patients: Drug Absorption and Distribution

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Obesity significantly alters the pharmacokinetic processes of drug absorption and distribution, presenting unique challenges in medical treatment. The increased fat tissue and decreased lean muscle in obese individuals can significantly affect how drugs are absorbed into the body and distributed across different tissues. This alteration can lead to variances in the effectiveness and safety of medications, necessitating adjustments in dosing or drug selection for obese patients.One notable...
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Drug Dosing: Obese Patients01:21

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In the United States, obesity is a prominent concern. It is linked to heightened mortality rates due to increased occurrences of conditions such as hypertension, atherosclerosis, coronary artery disease, and diabetes compared to nonobese individuals. A patient is classified as obese if their actual body weight surpasses the ideal or desirable body weight by 20%, based on Metropolitan Life Insurance Company data. Ideal body weights consider average weights and heights for males and females...
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Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion01:20

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Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
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Obesity01:24

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The Body Mass Index (BMI) is a numerical value derived from a person's weight and height, used to categorize individuals into weight ranges. It is calculated using the formula: weight in kilograms divided by height in meters squared. Obesity is a health condition characterized by excessive accumulation of adipose tissue that poses health risks, often diagnosed with a BMI ≥ 30. This excess fat storage occurs when surplus dietary calories are converted into triglycerides and stored in...
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Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
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Glucagon-like Receptor Agonists01:24

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Multidisciplinary Approach to Obesity Management: A Case Report
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Obesity medications in development.

Candida J Rebello1, Frank L Greenway1

  • 1Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.

Expert Opinion on Investigational Drugs
|December 19, 2019
PubMed
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Developing new obesity pharmacotherapies is critical due to neurobiological resistance to weight loss. Combining drugs targeting multiple pathways, including peripheral ones, may enhance efficacy and minimize side effects for effective obesity treatment.

Keywords:
DGAT-1DiabetesFGF-21IncretinMetAP2 AgonistsMetabolic SyndromeSGLT-2Sirt-1/AMPKneurotransmitter reuptake inhibitors

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Area of Science:

  • Pharmacology
  • Endocrinology
  • Neurobiology

Background:

  • Obesity presents a significant challenge due to complex neurobiological factors that impede weight loss.
  • Dysregulation of energy homeostasis necessitates the development of targeted pharmacotherapies.

Purpose of the Study:

  • To review clinical trial evidence for pharmacologic obesity treatments, including unapproved medications.
  • To provide expert opinion on the future of anti-obesity drug development.
  • To examine mechanisms of action for various drug classes, including GLP-1 agonists and CNS-acting agents.

Main Methods:

  • Literature search of PubMed and ClinicalTrials.gov using terms 'Obesity AND Medications'.
  • Inclusion of clinical trials reported in English.
  • Focus on medications evaluated in clinical trials, including those not yet FDA-approved.

Main Results:

  • Review of clinical trial outcomes for various anti-obesity medications.
  • Analysis of mechanisms including glucagon-like peptide-1 (GLP-1) agonists, co-agonists, and CNS/peripheral agents.
  • Identification of potential therapeutic strategies for obesity pharmacotherapy.

Conclusions:

  • The primary goal of anti-obesity therapy is to achieve efficacy with minimal side effects.
  • Combining pharmacotherapies that target multiple redundant pathways driving obesity can increase effectiveness.
  • Targeting peripheral mechanisms may be crucial to overcome limitations of centrally acting drugs in obesity treatment.