Pharmacology: Obesity PDF NMT200 Case Study

PHARMACOLOGY: OBESITY Dr. Adam Gratton NMT200 MSc ND September 11, 2023 LECTURE COMPETENCIES 1. Compare and contrast the mechanisms of action, indications, and adverse effects of drugs to treat obesity a. Incretin mimetics – semaglutide, liraglutide b. Appetite suppressants...

PHARMACOLOGY: OBESITY Dr. Adam Gratton NMT200 MSc ND September 11, 2023 LECTURE COMPETENCIES 1. Compare and contrast the mechanisms of action, indications, and adverse effects of drugs to treat obesity a. Incretin mimetics – semaglutide, liraglutide b. Appetite suppressants - bupropion c. Lipase inhibitors - orlistat 2. Recall commonly used medications that are known to cause weight gain as an adverse effect 3. Appraise and describe key details of published evidence regarding the use of incretin mimetics for weight loss RESOURCES Two course resources Golan’s Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy 4th Edition - Available through the LRC website – LWW Health Library Canadian Pharmacists’ Association CPS: Therapeutic Choices 2021 - Available through the LRC website – CPS Full Access INTRODUCTION Complex chronic condition and no single management strategy works for every patient Psychosocial, emotional, or physical barriers make it difficult for patients to engage in various management strategies There is no cure Until recently, there were no medications specifically indicated for obesity GOALS OF THERAPY The overall aim is to reduce excess body fat for health and not for cosmetic reasons; reducing weight by 5–10% can result in important health benefits At a minimum, the goal is to stabilize and prevent further weight gain Prevent weight regain Prevent and treat obesity-related comorbidities and complications TREATMENT PHASES Induction of weight loss – achieved through caloric restriction Prevention of weight regain – countering the neurobehavioural changes that seek to restore body weight to its original level DRUGS ASSOCIATED WITH WEIGHT GAIN Antidepressants - Particularly tricyclic antidepressants - E.g., amitriptyline associated with approximately 1.8 kg weight gain during the first three months of therapy with slower increases thereafter Antipsychotics - Both first and second generations - between 9 and 12 kg Corticosteroids - E.g., prednisone – an average of 2 kg during a 6-month daily course of therapy DRUGS ASSOCIATED WITH WEIGHT GAIN Antihyperglycemic drugs - E.g., sulfonylureas, meglitinides, thiazolidinediones – up to 5 kg during 3 – 12 months of treatment - E.g., insulin – up to 8 kg during intensive 3-month course of therapy Lithium - Used to treat mania – 10 kg or more in 6 – 10 years of therapy PHARMACOLOGIC CHOICES Lifestyle modification and anti-obesity therapy is superior to lifestyle modification alone in achieving a target weight loss of 5 – 10 % over the long term Discontinuation of anti-obesity medication generally results in weight regain APPETITE SUPPRESSANTS Bupropion alone or in combination with naltrexone are the only options approved in Canada Bupropion is a sympathomimetic drug and is given as a sustained- release formula and used as an antidepressant and smoking cessation aid According to evidence, 300 mg for 24 weeks is associated with a net weight loss of 2.2%; 400 mg with 5.1% Weight loss was maintained for 48 weeks APPETITE SUPPRESSANTS Bupropion/naltrexone Indicated for weight management alongside diet and exercise for those with a BMI of 30 or higher (27 if weight-related comorbidity present) Mediates hormones involved in appetite and reward Net weight loss of 4.2% over 48 weeks ADVERSE EFFECTS - BUPROPION Dry mouth, constipation, agitation, insomnia, anxiety Can cause seizures in rare instances with higher doses Caution in patients with hepatic impairment ADVERSE EFFECTS - COMBINATION Nausea, vomiting, constipation, headache, dizziness, insomnia, dry mouth Contraindicated with concurrent opioid therapy (due to precipitation of opioid withdrawal) Patients must be opioid free for 7 days prior to initiation of treatment CAUTIONS Avoid concurrent use of drugs that lower the seizure threshold. Minimize or avoid alcohol consumption. Avoid consumption with a high-fat meal. Avoid in patients with uncontrolled hypertension, seizure disorder, severe hepatic impairment, or end-stage renal failure. LIPASE INHIBITORS Orlistat Pancreatic and gastric lipase inhibitor that reduces dietary fat absorption by 30% For an average diet of 60 g of fat per day, results in 180 kcal/d reduction Compared to placebo: 2.9% additional weight loss over 1 year ORLISTAT – ADVERSE EFFECTS Oily spotting, flatus with discharge, fecal urgency. Decreased absorption of fat-soluble vitamins Contraindicated in patients with chronic malabsorption syndrome or cholestasis. ORLISTAT - CAUTIONS Advise patients to take a multivitamin daily ≥2 h before or after orlistat or at bedtime A high fat intake is poorly tolerated Less effective in patients on low-fat diets and is difficult to take for individuals with irregular eating patterns INCRETIN MIMETICS The two major incretin hormones in humans are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) They are responsible for most of the glucose-induced insulin secretory response following glucose ingestion Both are metabolized by the enzyme dipeptidyl peptidase 4 (DPP4) INCRETIN MIMETICS GLP-1 is also responsible for the reduction of food intake and appetite, increased satiety, and decreased gastric emptying GLP-1 also affects reward-related systems in the brain GIP has less effect on other organs, but also delays gastric emptying and seems to play a role in fat deposition LIRAGLUTIDE GLP-1 agonist Administered by subcutaneous injection Originally approved for type 2 diabetes and then rebranded for obesity 3 mg SC can induce 8 kg of weight loss over 2 years of therapy in conjunction with lifestyle measures ADVERSE EFFECTS Nausea, vomiting, constipation, and diarrhea are most common Gastrointestinal side effects can be minimized by a slow titration. Can cause pancreatitis in rare instances Severe hypoglycemia observed in patients with type 2 diabetes; adjustment of diabetes medications may be required CAUTIONS Caution in patients with heart rhythm disturbances, hepatic insufficiency, and severe renal impairment. Should not be used in inflammatory bowel disease. Contraindicated in pregnancy, breastfeeding, personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2). Discontinue after 12 weeks if body weight loss