Lecture 3 Endocrine and Metabolic Disorders “Obesity” University of Nizwa College of Pharmacy and Nursing School of Pharmacy PHARMACOTHERAPY II PHCY 410 Lecture 3 Endocrine and Metabolic Disorders “Obesity” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

Course Outcomes Upon completion of this lecture the students will be able to Describe etiology and diagnostic parameters of obesity. Develop skills to monitor drug therapy obese patients. Develop pharmaceutical care plan for managing patients with obesity.

Obesity is a complex disorder that places individuals at increased risk for health problems from excess body fat. Body mass index defines people as overweight (pre-obese) when their BMI is between 25 kg/m2 and 30 kg/m2, and obese when it is greater than 30 kg/m2. Waist circumference is another measure of abdominal obesity, in which values exceeding 102 cm in men and 88 cm in women, are markers of increased cardiometabolic risk. Strategies for Obesity Treatment There is currently no “cure” for obesity, so there should be a long-term “coping” strategy that allows the patient to reduce their body weight and prevent weight regain.

ETIOLOGY Multifactorial-and related to varying contributions from genetic, environmental, and physiologic factors. Environmental factors include reduced physical activity or work; abundant and readily available food supply; increased fat intake; increased consumption of refined simple sugars; and decreased ingestion of vegetables and fruits. Weight gain can be caused by medical conditions (e.g., hypothyroidism, Cushing’s syndrome, hypothalamic lesion) or genetic syndromes. Medications associated with weight gain include insulin, sulfonylureas, and thiazolidinediones for diabetes, some antidepressants, antipsychotics, and several anticonvulsants.

Phase 1: Induction of weight loss Weight loss requires caloric restriction, and a negative energy balance of 500 kcal/day results in weight loss of 1 to 2 kg per month. Caloric restriction should continue until the patient achieves the weight-loss plateau (3-6 months), at which time phase 2 starts. Phase 2: Prevention of weight regain The induction of weight loss results in complex hormonal and neurobehavioural changes toward restoring body weight again. So, the patient should continue restricting his energy intake and do some lifestyle changes like increasing his physical activity.

Investigations 1) Weight history: - Previous attempts at weight loss. - Contributing factors (e.g., steroids, antihyperglycemic, anticonvulsant or antipsychotic medications). - Lifestyle (diet and activity). 2) Family history of obesity and comorbidities 3) Physical examination: - Weight, height, and waist circumference, calculate BMI - Vital signs 4) Laboratory tests - Screening for hypertension, diabetes mellitus, dyslipidemia, and gout.

Therapeutic Choices Nonpharmacologic Choices 1) Nutrition Planning and Diet Composition Regular eating (3 meals, 3 snacks), and discourage prolonged fasting and skipping of meals. Carbohydrate intake should be ≥ 100 g/day (400 kcal/day) to avoid protein breakdown and muscle wasting. Protein intake should be ≥1 g/kg/day of mixed proteins to maintain lean body mass and essential body functions. Fat intake should not exceed 30 to 35% of total calories.

2) Physical Activity Encourage all patients to spend ≥30 minutes of continuous or intermittent exercises at least 5 days/week. The initial goal is to increase energy expenditure by 700 kcal/week or about 100 kcal daily. Exercise coupled with a proper caloric-deficit meal plan accelerates fat loss while maintaining lean body mass, and helps sustain weight loss over the long term. Physical activity would also enhance the patient's sense of well-being, improves insulin resistance and reduces the loss of bone mineral density that is associated with weight loss. However, exercise alone is not effective for weight loss.

Pharmacologic Choices Discontinuation of anti-obesity drugs results in weight regain, and so, it should be continued for as long as there is a benefit. 1) Appetite Suppressants Bupropion is a sympathomimetic drug that has a mild appetite-suppressant effect and can be used for short-term weight loss. 2) Satiety Enhancers Sibutramine, a serotonin and norepinephrine reuptake inhibitor (SNRI), primarily acts by increasing the sense of satiety after meals, thereby allowing patients to reduce portion size and avoid snacking between meals.

3) Lipase Inhibitors Orlistat is a pancreatic and gastric lipase inhibitor that reduces dietary fat absorption by 30%. A high fat intake is poorly tolerated during orlistat therapy because of an increased incidence of bloating, steatorrhea and oily discharge, however, orlistat is less effective in patients on low-fat diets. Orlistat is approved for use in obese patients with type 2 diabetes mellitus, in whom it improves glycemic and metabolic control.

EVALUATION OF THERAPEUTIC OUTCOMES Requires careful clinical, biochemical, and, if necessary, psychological evaluation. Progress should be assessed in a healthcare setting once or twice monthly for the first 1 to 2 months, then monthly. Document weight, WC, BMI, blood pressure, medical history, and tolerability of drug therapy on each encounter. Medication therapy should be discontinued after 3 to 4 months if the patient has failed to demonstrate weight loss or maintenance of prior weight. Diabetic patients require more intense medical monitoring and self monitoring of blood glucose. Some anorectic agents have direct effects that improve glucose tolerance.