Allen - Evaluation and Treatment of Obesity
Transcription
Allen - Evaluation and Treatment of Obesity
6/21/2016 Presented by Evaluation and Treatment of Obesity Robert F. Allen, MD July 1‐3, 2016 Sandestin Golf & Beach Resort Neurology Evaluations, PC Evaluation and Treatment of Obesity 1 6/21/2016 Robert F. Allen, MD Weight Management Clinic ( A division of Neuro-Eval, P.C. ) 105 N. Pontiac Ave, Suite 1 Dothan, AL 36303-3959 rfa7255 @ hotmail.com Our Prescribing Seminar includes Obesity Management because: 1) Obesity is a major health issue 2) Numerous risks & co-morbidities 3) Anorexiants are Schedule III-IV 4) FDA / DEA laws and guidelines 5) Alabama Board Medical Examiners “Rules for Prescribing Anorexiants” (540-X-17), in force January, 2012 2 6/21/2016 OUTLINE OF TOPICS ------------------------------------------------------------------------ 1) Definitions 2) Measurements 3) Demographics 4) Contributors 5) Adipose Cells 6) Comorbidities 7) Mortality risks 8) Evaluations 9) Treatments 10) Anorexiants 11) ABME Rules 12) Limitations I. OBESITY DEFINITIONS 3 6/21/2016 June 18, 2013 ”Obesity is a disease state with multiple pathophysiology aspects, requiring a range of interventions to advance treatment and prevention.” MY BEST DEFINITION: Obesity is a multi-factorial complex disease state which encompasses genetic, environmental, metabolic, physiological, behavioral, psychological, social & cultural factors … 4 6/21/2016 … and is associated with increased risks of numerous medical conditions: diabetes mellitus type II, dyslipidemias, hypertension, coronary artery disease, TIA/stroke, renal disorders, cancers, obstructive sleep apnea, asthma, gall bladder diseases and surgery, arthritis, gout, DJD spine/hips/knees, PCOS, reproductive disorders, etc. II. OBESITY MEASUREMENTS 5 6/21/2016 Underwater Weighing Skinfold Calipers Dual-Energy X-ray Absorpitometry (DXA / DEXA) Bio-Impedance Analysis (BIA) Near-Infrared Reflectance (NIR) Body Mass Index (BMI) Abdominal Girth Measurement Waist-to-Hip Ratio (W:HR) Underwater Weighing Hydrostatic testing Basis: Fatty tissue floats Lean tissue sinks This is the gold standard for “Body Fat Percentage” in clinical obesity research. But: Clearly, not practical in a clinical office setting. 6 6/21/2016 Skinfold Calipers Measure skin-fold thickness over several (9 to 24) areas. Measurements are entered in tables or formulas to yield a body fat analysis. Limitations of calipers: 1) Time-consuming (measures & data entry); 2) Subject to human variability in technique; 3) Wide range of values (>90 formulas). DXA (Dual-Energy X-ray Absorpitometry) A direct measure of minerals and thus, primarily a bone density study (osteopenia). Also measures lean mass. Fat tissue mass is obtained by calculation: Total mass - mineral and lean mass = body fat mass (An accurate but expensive method) 7 6/21/2016 Near-Infrared Reflectance A fiberoptic probe sends an Infrared light signal through a muscle. The light is reflected off the underlying bone and back to the signal detector. Reflectance is proportional to the degree of underlying fat content. Sources of error in NIR: 1) edema; 2) dehydration; 3) skin color; 4) patients in the higher obesity range; 5) technician’s applied pressure on the probe. Bio-Impedance Analysis (BIA) Painless electrical current passes through grounded body. 1) Lean tissues (skin, muscles, bone) conduct the current. 2) Fatty tissues act as insulation, do not conduct the current. Yield= BODY FAT PERCENT Operator-independent, safe and easy to use. Floor models are affordable ($1,800-2,500); hand-held models less reliable. 8 6/21/2016 Body Mass Index (BMI) A calculation: total body weight (TBW) ___________________________________________________________________ body surface area (BSA) BSA is estimated by the square of the height. BMI is based on TBW, and cannot distinguish fatty tissue from lean tissue. Calculating the BMI National Institutes of Health, Consensus Conference, 1991 Metric: BMI = Wt (Kg) / Ht (M2) English: BMI = Wt (Lb) x 704 / Ht (In2) Example: A 5’6” female weighs 196 pounds. BMI = 196 pounds x 704 66” x 66” = 136,788 / 4,356 = 31.6 9 6/21/2016 BMI Chart National Institutes of Health, Consensus Conference, 1991 CALCULATED BMI > 40.0 35.0 – 39.9 30.0 – 34.9 27.0 – 29.9 25.0 – 26.9 18.5 – 24.9 < 18.5 CLASSIFICATION Obese III Obese II Obese I Overweight II Overweight I Normal Underweight Advantages of BMI over other obesity rating methods: Inexpensive (requires no special equipment) Anyone can perform (you only need the patient’s weight, height, and a calculator) Convenient (many scales are equipped to perform the BMI calculation at weigh-in) Patient progress easily followed over time Correlates closely with body fat (vs. underwater weighing) in ~92% of people 10 6/21/2016 Inaccuracies in BMI BMI may over-estimate body fat when: NUMERATOR (total body weight) is larger but non-fat: Athletes / body builders extra weight from muscle Edematous states extra weight is from fluid Pregnancy extra weight of fetus, placenta, fluid DENOMINATOR (height ²) is smaller < 5’2” (female) or < 5’5” (male) BMI may under-estimate body fat in: Sarcopenic obesity – increase in abdominal fat, coupled with a loss of muscle mass in the limbs (a condition especially common in the elderly) 11 6/21/2016 Abdominal Girth Measurement BMI alone cannot determine unhealthy central fat content. The largest girth of the abdomen gives a good estimate of intra-abdominal fat. BE CONSISTENT: I always measure with the patient in a seated position, to avoid “holding in.” DANGER LEVELS: NIH Expert Panel Report, Am J Clin Nutr 1998; 68:899-917 Females: >35” Males: >40” Waist-to-Hip Ratio (W:HR) “apple” “pear” or android (male-like) Males > 1.0 0.96 – 1.0 < 0.95 or gynoid (female-like) Health Risks Based Solely on W:HR Higher Risks Moderate Risks Lower Risks Females > 0.85 0.81 – 0.85 < 0.80 12 6/21/2016 The Take-Home Message on Measurements “ BMI’s and Belly Size ” It should take about one (1) minute to: a) obtain the weight and height, b) calculate the BMI (body mass index), c) measure the abdomen and hips, d) calculate W:HR (waist-to-hip ratio), e) enter these values in the record. When used together, BMI, abdominal girth and W:HR are the best predictors of future health complications resulting from excess central (abdominal) fat. III. OBESITY DEMOGRAPHICS 13 6/21/2016 South Pacific Islands Actual Postcards for Sale 14 6/21/2016 Highest Obesity Rates on Earth Global Obesity Rates Russia and Former SSR’s Iceland UK Canada 32% → USA Mexico Cuba Central America South Pacific Islands Ireland Spain Portugal Eastern Europe Middle Dominica Caribbean Iran East Barbados Venezuela South Pacific Islands Maldives Ecuador Seychelles Australia Chile Uruguay Argentina Republic of South Africa New Zealand OBESITY (BMI>30) RATES South Pacific Islands Middle East United States & Mexico 55-75% > 60% > 32% 15 6/21/2016 World Population Milestones Population 1 billion 2 billion 3 billion 4 billion 5 billion 6 billion 7 billion 8 billion 9 billion 10 billion Year 1804 1927 1959 1974 1987 1999 2011 est. 2024 est. 2037 est. 2050 Interval dawn of humans 123 years later 32 years later 15 years later 13 years later 12 years later 12 years later 13 years later 13 years later 13 years later As of July 2, 2016 World Population: 30% Overweight: 13% Obese: USA Population: 7,463,000,000 2,230,000,000 970,000,000 324,500,000 68% Overweight: 220,000,000 32% Obese: 104,000,000 16 6/21/2016 USA Obesity Prevalence - 2016 >20% >25% >30% 2002 2004 2006 *47.6% * * ** * * * 2008 2010 2012 17 6/21/2016 Obesity Rate by County, 2012 IV. CONTRIBUTORS to OBESITY 18 6/21/2016 Contributors to Weight Gain DIETARY FACTORS Consuming more calories than used Larger portions (restaurants, fast food, home) Eating with friends / family who overeat Reliance on “low fat” yet high-calorie foods Inadequate dietary fiber (= “not full”) Sugary sodas, sports drinks, beers, cocktails Eating too fast (belly brain = 20 min) Skipping meals during the active hours, only to overeat at the end of the work day Contributors to Weight Gain LIFESTYLE FACTORS Entrenchment in a sedentary lifestyle (sitting: work, desk, computer, TV, traffic) Lack of daily cardiovascular exercise Marriage, moving, marital discord, divorce Stopping smoking (avg gain 4-30 pounds) Longer work hours, overtime, 2+ jobs Shift work, sleep irregularities Going on vacation (dietary changes?) Paying for meals with credit cards 19 6/21/2016 Contributors to Weight Gain MEDICAL FACTORS Genetics (obese parents, other family) Overweight or obese as a child or young teen (prepubertal obesity leads to an increase in number and size of fat cells) Low BMR (basal metabolic rate) which decreases ~1% per year after 30 Hypothyroidism (up to 10% of women) Life stressors, anxiety, depression Cushing’s syndrome (cortisol effect) Sleep apnea or other insufficient sleep Contributors to Weight Gain MEDICAL FACTORS Polycystic ovarian syndrome (PCOS) Menopause (+5-15 pounds, low abdominal) Essential fatty acid deficiencies Renal or hepatic insufficiency Hysterectomy, especially with bilateral oophorectomy, > with hormonal therapy Fibromyalgia (and associated conditions) Rare syndromes (Prader-Willi, Bardet-Biehl, Cohen, Albright, Fragile X, Carpenter) 20 6/21/2016 Drugs Weight Gain Hormones – Depo-Provera®, estrogens, OCP’s Antidepressants – all Tricyclics, all MAOI’s, most SSRI’s (Paxil, Zoloft, Celexa, Lexapro, Luvox), Cymbalta, Lithium carbonate, Desyrel (trazodone), Sinequan (doxepin), Effexor, Pristiq, Remeron Proton Pump Inhibitors (PPI’s) – (Prilosec, Nexium, Prevacid, Aciphex, Protonix, Zegerid) Beta-blockers – propanolol, atenolol, metoprolol Medications for Diabetes – all insulins; > sulfonylureas: Glucotrol (glipizide), Amaryl (glimeperide) > glyburides: (DiaBeta and Glynase) > thiazolidindiones: (Actos, Avandia, Regulin) Weight Change in Antidiabetic Therapy Weight change (kg) Insulin 7 6 5 Sulfonylurea Glyburides 4 3 2 Diet alone 1 Metformin 0 Invokana® -1 2 4 6 8 10 Years of treatment 21 6/21/2016 Drugs Weight Gain Anticonvulsants – (Depakote, Neurontin, Tegretol, Carbatrol, Trileptal, Lyrica, Vigabatrin) Calcium-channel blockers – verapamil Anti-Allergy meds – (mainly with chronic use) – Periactrin, Claritin, Allegra, diphenhydramine Antineoplastics – tamoxifen, aromatase inhib’s, methotrexate, cyclophosphamide, 5-fluorouracil Antiretrovirals – Protease inhibitors (all) Antipsychotics – Clozaril, Zyprexa, Thorazine, Stelazine, Mellaril, Navane, Seroquel, Risperdal, Haldol, Abilify, Permitil, Geodon) 22 6/21/2016 Drugs Weight Reduction Metformin (Glucophage®): diabetes mellitus type II, PCOS; ADA Metformin can prevent clinical DM II if BMI > 35. SGLT2 inhibitors – (Invokana®, Farxiga® and Jardiance®); glycosurics for treatment of diabetes mellitus type II. Exentanide (Byetta ®) and Liraglutide (Victoza®): DM-II; delayed gastric emptying, stomach fullness, nausea. Buproprion (Wellbutrin®): depression, (Zyban®): smoking; Choice antidepressant in obese; 100, 150, 200, 300mg. Do not combine with dopaminergic anorexiant Tenuate®. Fluoxetine (Prozac®): anxiety, (Sarafem®): pre-menstrual; 20-60 mg daily if taken alone; 10-40 mg daily if combined with anorexiant, preferably Tenuate® (diethylproprion). Topiramate (Topamax®): migraine prophylaxis, epilepsy; weight reduction dose 50-100 mg daily; CNS side-effects. Zonisamide (Zonegran®): anticonvulsant, anti-migraine; weight loss often with preventive doses 100-200 mg daily. V. FAT CELLS FUNCTIONS 23 6/21/2016 A Fat Cell – Classic View ___ 24 6/21/2016 In 1950, there arose a mutant strain of mice with excess eating, weight gain and diabetes, suggesting the existence of a hunger-reducing hormone (Leptin). Obese mouse, (ob-ob) unable to produce Leptin Normal mouse, able to produce adequate Leptin 1994: the ob gene was isolated to mouse Chromosome 6 and human Chromosome 7q. Obese humans DO NOT have leptin deficiency. Obese humans show desensitization of leptin receptors in the arcuate nucleus of the hypothalamus. Leptin is the most important hormone produced by adipose cells, with a major role in regulating hunger, appetite, eating behavior, and energy expenditure. Leptin acts on receptors in the arcuate nucleus of the hypothalamus (the “satiety center”) to decrease appetite, meal size and frequency. Counteracts the hunger-producing effects of: ghrelin (the “hunger hormone”) from the gut neuropeptide-Y from hypothalamus and gut Aids metabolism and energy expenditure by stimulating leptin receptors in the periphery 25 6/21/2016 INCREASED BODY FAT Effects of Fat Mass Distant Effects of Fat Obstructive apnea Fatty liver diseases Added weight/inch² on feet, ankles, knees, hips, SIJ’s DJD (weight-bearing joints) Protrusion of the center of gravity Low back pain/strain Diabetes type II Endothelial diseases: CAD, MI, TIA, stroke Hyperlipidemias Solid cancers Inflammatory arthritis (NWBJ’s) and gout Adult asthma PCOS, infertility 26 6/21/2016 ADIPOSOPATHY (“sick fat syndrome”) Products of fat cells contribute to: Hunger, appetite, caloric intake and satiety Glucose regulation, transport and storage Insulin regulation, sensitivity and resistance Lipid absorption, metabolism and storage Hypertension, vasoconstriction, vasodilation Thirst, salt regulation and renal function Inflammatory processes in many tissues Endothelial malfunctions and CAD/CVD/PVD Brain and nervous system malfunctions Excessive Body Fat Alters the body’s response to insulin Potentially leads to insulin resistance Is widely present among diabetics: 77% of women and 64% of men with DM type II are overweight or obese Creates a pro-thrombotic state Associated with CAD, MI, stroke, TIA, PAD Creates a pro-inflammatory state Associated with asthma, osteoarthritis, gout 27 6/21/2016 Metabolic Syndrome Central adiposity: belly circumference Dyslipidemia: triglycerides >150 Hypertension: Hyperglycemia: Hyperinsulinemia: Insulin resistance: Diabetes type II: Males >40 inch Females >35 inch HDL <40 HDL <50 pressure >135/85, or taking bp med fasting glucose >110 or A1C > 7.0 fasting insulin >15 abnormal GTT end-organ diseases VI. COMORBIDITIES of OBESITY 28 6/21/2016 Obesity and Diabetes type II Risk in Women (Nurses’ Study) 100 115,195 women, studied for 14 years 93.2 75 54.0 50 40.3 27.6 25 15.8 4.3 5.0 8.1 1.0 2.9 <22 2222.9 2323.9 2424.9 2526.9 0 27- 2928.9 30.9 3132.9 3334.9 35+ BMI (kg/m2) Colditz et al. Ann Intern Med 1995; 122: 481-6 Diabetes by county, (2008) ___________________ Obesity by county, (2008) 29 6/21/2016 Comorbidities of Obesity ENDOCRINOLOGY Diabetes mellitus type II Polycystic ovarian syndrome Menstrual disorders Infertility (female and male) Intrauterine fetal death Increased birth defects risks (anencephaly, hydrocephaly, spina bifida, heart defects, cleft palate, cleft lip) Pregnancy / delivery complications (C-section) Comorbidities of Obesity CARDIOVASCULAR Hypertension Coronary ischemic disease Congestive heart failure Atrial fibrillation / arrhythmias Cardiomyopathy of obesity (adipositas cordis) Elevation of triglycerides and cholesterol, abnormal fractions Elevation of serum triglycerides Deep venous thrombosis Pulmonary embolism 30 6/21/2016 Comorbidities of Obesity NEUROLOGY Stroke and TIA Intracranial hypertension (pseudotumor cerebri) Nerve compressions: Carpal tunnel syndrome (wrist) Meralgia paresthetica (thigh) Tarsal tunnel syndrome (ankle) Multiple sclerosis (esp in obese adolescents) Migraines (esp the chronic daily form in females) Dementia (increase of 42-80%) Johns Hopkins Univ, Sch Pub Health “ Obesity Can Increase Dementia Risk By Up To 80 Percent,” Study, (May 7, 2008). Comorbidities of Obesity Obstructive sleep PULMONOLOGY apnea (OSA) Adult asthma Cor pulmonale Hypoventilation (CO2 retention) Respiratory failure 2° Pulmonary hypertension Complications during general anesthesia 31 6/21/2016 Comorbidities of Obesity GASTROENTEROLOGY Gastro-Esophageal Reflux Disease (GERD) Non-Alcoholic Steato-Hepatitis (NASH) Non-Alcoholic Fatty Liver Disease (NAFLD) Gall bladder disease (stones, cholestasis, cholecystitis) Increased incidence and earlier age of cholecystectomy Gallstone-induced pancreatitis Gastrointestinal cancers: Liver, gall bladder, colon and anorectal Comorbidities of Obesity RHEUMATOLOGY Marked increase in gout and osteoarthritis in general Earlier onset DJD in weight-bearing joints (feet, ankles, knees, hips, sacroiliac joints) Lumbar degenerative discs Low back pain: protuberant abdomen results in forward shift of the center of gravity with compensatory lumbar muscle strain Myofascial pain syndrome (formerly fibromyalgia) 32 6/21/2016 Comorbidities of Obesity ORTHOPÆDICS Total hip replacement: Increased need, earlier intervention (up to 10 years sooner if BMI ≥ 35) Longer surgery/rehab, or worse outcome Total knee replacement: Increased need, earlier intervention (risk ratio of 6.6 if the BMI ≥35) Longer surgery, 2x infections, longer rehab Impaired mobility and falls Devices (cane, walker, wheelchair, scooter) Obese pediatric population: Malalignment in legs, increased fracture risk Comorbidities of Obesity GENITOUROLOGY Chronic renal failure (CRF) Renal stones (♀ > ♂) Urinary incontinence Renal cell carcinoma Diseases of the prostate (prostatitis and pain) Prostate cancer (57% increase in incidence, more aggressive tumors, increased morbidity, earlier mortality when BMI>35) Secondary male hypogonadism / hypotestosteronism, erectile and/or ejaculatory dysfunctions 33 6/21/2016 Comorbidities of Obesity PSYCHIATRY Altered self-image low self-esteem, shame Embarrassment social isolation/seclusion Anxiety related to body size/image may paradoxically lead to binge-eating Depression is more common among the obese …but suicide attempts are less common Adverse effects on relationships (marital, family, work, social) and academic achievement Obesity stigma (present at any age, but often most severe in obese children) Teasing, name-calling, bullying (and retribution) Comorbidities of Obesity ONCOLOGY (Relative risks, as compared with persons with BMI <25) Solid Cancers Liver Endometrium Esophagus Renal cell Colorectal Gallbladder Stomach Pancreas Prostate Breast (post-menopausal) BMI >25 BMI >30 1.5 2.0 2.0 1.5 1.5 1.5 1.5 1.3 1.3 1.3 4.0 3.5 3.0 2.5 2.0 2.0 2.0 1.7 1.6 1.5 34 6/21/2016 Comorbidities of Obesity DERMATOLOGY Striae Psoriasis Cellulitis Lymphedema Hirsutism Intertrigo Acanthosis Hyperkeratosis Consequences of Obesity HEALTH CARE BIAS Obese patients who experience stigma in health-care settings may forego or delay essential preventive care, including age-appropriate screenings for breast, cervical and colorectal cancer. Wee CC, et.al. Screening for cervical and breast cancer: Is obesity a barrier to preventive care? Ann Intern Med 2000; 132: 699–704. When asked about specific reasons for delay of care, women reported disrespectful treatment and negative attitudes from providers, embarrassment about being weighed, receiving unsolicited advice to lose weight, and chairs, gowns and exam tables, etc., too small to be functional. These concerns increased as BMI increased. Amy NK, Aalborg A, Lyons P, Keranen L. Barriers to routine gynecological cancer screening for White and African-American obese women. Int J Obes 2006; 30: 147–155. NOTE! Providers, please increase your awareness of the complex nature of obesity, and be more supportive. 35 6/21/2016 VII. OBESITY MORTALITY All passengers and crew on both planes are killed ! Total dead: 1,000 This is what OBESITY is doing in America every day. 36 6/21/2016 435 365 98 75 60 52 42 26 24 Relative Risk Relative Risk of Mortality ofbyMortality BMI by BMI 37 6/21/2016 Years of Life Lost (YLL) as a Function of BMI Weight Class BMI Years Lost ________________________________________________________ __________________ ______________________________________________ <19 19-25 >27 >30 >35 >40 >50 Variable Reference 2-3 years 4-5 years 6-7 years 8-9 years 12-16 years Underweight Normal Overweight Obese I Obese II Obese III Extreme Obesity VIII. OBESITY EVALUATIONS 38 6/21/2016 Medical History Items of Importance in Obesity Weight Gain History, Onset, Pattern Previous Weight Loss History and How? Dietary History (what & how much) Exercise History (how active & how often) Past Medical / Psychiatric History Pregnancies (and weight gain during…) Habits, Addictions, Bulimia, Anorexia Current and Previous Medications Family (Obesity and Comorbidities) Evaluation of Obesity PHYSICAL EXAM WEIGHT, BMI, BODY FAT % (for classification) VITAL SIGNS (hypertension, tachycardia) HEENT Facial redness/puffiness Cushing’s disease Hirsutism PCOS, Cushing’s Periorbital edema, thinning of lateral eyebrows, scalloped tongue hypothyroidism Erosion of dental enamel, swollen parotid glands consider bulimia nervosa Vertical nystagmus low magnesium NECK Circumference > 17”M, > 16” F (sleep apnea) Enlarged thyroid/masses/nodules Buffalo hump Cushing’s disease, steroids 39 6/21/2016 Evaluation of Obesity PHYSICAL EXAM HEART Rhythm abnormalities, murmurs ABDOMEN Girth measurement (abnormal > 40” M, > 35” F Waist:Hip ratio (high risk: > 1.0 M, > 0.85 F Tenderness, ascites, umbilical hernia EXTREMITIES AND SKIN Edema from CHF, renal insufficiency, liver disease Muscle weakness myasthenia gravis, Cushing’s Dry, cracked heels diabetes, hypothyroidism, essential fatty acid deficiency (linoleic, α-linoleic) Deep Tendon Reflexes Delayed relaxation phase hypothyroidism Hyperactive low magnesium Evaluation of Obesity LABORATORY TESTING Basic Laboratory Work-Up Metabolic panel Lipid profile CBC w auto diff Vitamin D level T3, T4, TSH Urinalysis Other Tests when Indicated EKG/Cardiac testing Polysomnography Hormone levels Hgb A1c, GTT Uric acid Serum Mg++ Other Considerations of Relevance in Obesity Insulin resistance Pre-diabetes Diabetes type II Metabolic syndrome Hyperlipidemia Hypothyroidism Vitamin D def. Cushing’s synd. Fatty liver Cancers PCOS Low Mg++ 40 6/21/2016 IX. OBESITY TREATMENTS 41 6/21/2016 Dietary Guidelines RCD (reduced calorie diets) – Most of the successful weight loss diets include a reduction in calories, a marked reduction in carbohydrates (SugarBusters, Atkins, Weight Watchers, South Beach, The Zone, Mediterranean, American Diabetic Association, etc.), elimination of saturated fats, modest reduction in unsaturated fats; maintain adequate intake of protein, fiber, water, antioxidants, and essential vitamins. LCD (low calorie diets, ≤ 1200 Cal/day) include meal replacements (shakes, cookies, chips, soups) plus one limited-calorie, low carb meal per day. VLCD (very low calorie diets, ≤ 600 Cal/day) include meal replacements (protein shakes). VLCD requires weekly visits / labs; vitamin / electrolyte supplements. These are best left to physicians with VLCD training. Activity Guidelines Weight maintenance in an adult requires at least 150 minutes of cardiovascular (aerobic) exercise per week ( = 22 minutes/day, 30 minutes 5 days/wk, or 50 minutes 3 days/week. EASY: While watching an hour of TV, stand and “march-in-place” only during commercials. Equals 22 minutes of cardio exercise. For faster loss, increase to 225-300 min/week. Moderate weight-lifting limits muscle loss. Gym memberships and group classes, although not required, often aid in exercise compliance. In order to avoid injury in the markedly obese, concentrate first on dietary change (with or without medications), add exercise later as tolerated. 42 6/21/2016 Activity Guidelines Calories Used in 22 Minutes Running Swimming Bicycling Aerobics Stairs Weights Walking Sitting 250 220 200 225 200 165 150 20 Lifestyle Guidelines Set a realistic weight loss goal for each interval: -4% @ week 5, -7% @ week 10, -10% @ week 15… Adhere to a grocery list and snack list. Pay close attention to ingredients and food preparation. Use smaller plates, bowls, spoons, glasses, bites. Keep a diary of intake and exercise (phone app’s). Limit meals that are consumed away from home. Ensure adequate sleep (at least 7 hours per 24). Commercial weight-loss programs (Weight Watchers, NutriSystem, Jenny Craig, Slim-Fast, Biggest Loser). Formal behavioral modification therapy may be useful for binge eating disorder, nocturnal eating syndrome, or prior history of anorexia or bulimia. 43 6/21/2016 NIH. www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf Common Obesity Surgeries 44 6/21/2016 X. OBESITY ANOREXIANTS GENERIC Methamphetamine Phenmetrazine Phendimetrazine Phentermine Diethylproprion Benzphetamine Phenylpropanolamine Fenfluramine Mazindol Chlorphentermine Dexfenfluramine Sibutramine Orlistat Phentermine-topiramate Lorcaserin Naltrexone-buproprion Liraglutide BRAND(s) DEA YR Desoxyn®, Hydrin® Preludin® Bontril®, Anorex® Adipex®, Ionamin® Tenuate®, Tepanol® Didrex®, Regimex® Dexatrim®, Accutrim® Pondimin® Sanorex®, Mazanor® Presate® Redux® Meridia® Xenical®, Alli® Qsymia® Belviq® Contrave® Saxenda® II II III IV IV III OTC IV IV IV IV IV Rx IV IV Rx Rx 1947 1954 1959 1959 1959 1960 1960 1973 1973 1973 1996 1996 1999 2012 2012 2014 2014 P W W W W W W W 45 6/21/2016 Anorexiants approved by FDA and ABME for use in Alabama Medication DEA Year Phentermine Diethylproprion Phendimetrazine Benzphetamine Qsymia® Belviq® Contrave® Saxenda ® Class IV Class IV Class III Class III Class IV Class IV Rx only Rx only 1959 1959 1959 1960 2012 2012 2014 2014 Phentermine ©IV 2-methyl-1-phenylpropan-2-amine The most frequently prescribed anorexiant 46 6/21/2016 CLINICAL PROPERTIES: 1) Anorexiant - Primary Noradrenergic effect: stimulates receptors in the hypothalamus to produce and release norepinephrine, leading to a catecholamine-induced “fight or flight” phenomenon that includes hunger reduction. 2) Metabolic – An Adrenergic effect: binds to β3 receptors (ADRβ3) on adipose cells to stimulate lipolysis (metabolism of stored fat). 3) Satiation - Weakly Serotonergic which leads to a sense of fullness with less food intake. 4) Thermogenic – Also an Adrenergic effect, stimulates peripheral receptors to produce increased calorie usage in skeletal muscle. Brands available: Adipex-P® 37.5 mg scored tab often dosed as 1/2 tab BID 37.5 mg capsule Ionamin® phentermine resin 30 mg, 15 mg cap Suprenza® oral-disintegrating unscored tablets 15, 30, 37.5 mg Several generics: Scored tab 37.5 mg (often dosed ½ tab BID) Capsule 37.5 mg Capsule 30 mg Capsule 15 mg Adult dosing (≥ 16 yrs of age). Lowest dose is 15 mg/ day. Frequent starting dose of 18.75 mg BID. Advance as needed to 30 mg AM, 15 mg afternoon, 30 mg BID (rarely 37.5 mg BID) 47 6/21/2016 Phendimetrazine ©III (Five decades as Bontril-SR® 105 mg capsules and Bontril-PDM® 35 mg tablets) The first non-Class II drug (1959) Mixed CNS effects (NE, 5HT, DA) O Now available in generics only. 105 mg sustained-release capsule to be taken once daily after first meal (acid-sensitive) 35 mg scored tablet, take TID before meals Sometimes SR 105 mg AM, 35 mg afternoon NOTE: The SR capsule is usually ineffective in persons after gastric bypass surgery due to poor absorption of the capsule. Benzphetamine ©III Highest anorexiant potency Noradrenergic (stimulates release of hypothalamic norepinephrine) Never a first-line anorexiant Available in brands: Didrex® 50 mg scored tablet Also available in generic: 50 mg scored tablet Regimex® 25 mg scored tab Always begin with 25 mg BID, titrate upward to a maximum 50 mg TID, taken 30 min prior to meals 48 6/21/2016 Diethylproprion ©IV (Tenuate Dospan® 75 mg, Tenuate® 25 mg Structurally similar to the antidepressant Buproprion Di-ethyl group Butyl group Tenuate ©IV diethylproprion Primary effect: dopamine release Blocks reuptake of norepinephrine Increases brain leptin (satiety) Reduces brain neuropeptide-Y levels (reduces hunger) Brands and quality generics available: Tenuate® 25 mg (immediate release tabs, TID before meals) Tenuate Dospan® 75 mg sustained-release tablet, taken once daily after the first meal Unique: Fully renal excretion Avoid: Using with buproprion Okay: With SSRI’s (no crossover) Okay: ≥12 years age (2002 PDR) Safest: With HTN - CAD - CVD 49 6/21/2016 Potential Adverse Effects of Older Anorexiants Tachycardia (1% ≥ 110 bpm) BP increase (avg ≤ 5 mm) Chest pain (rare) Dysuria, hesitation, frequency Low libido, anorgasmia (<2%) IOP (closed-angle glaucoma) Dry eyes (common) Dry mouth (common) Dry gut (constipation) Metallic aftertaste Sleeplessness Nervousness Tremulousness Irritability Mood changes Depression Pain/headache Body aches Sweating Thinning hair Long-Term Pharmacotherapy in the Management of Obesity National Task Force on the Prevention and Treatment of Obesity. JAMA 276(23): 1907-15 (Dec 1996). 60’s: FDA approved anorexiants for “short-term” use. 70’s: FDA requirements for longer-term therapy. Obesity is a chronic condition with long-term effects. Obesity responds poorly to short-term therapy. Anorexiant treatment for ≥ 24 weeks is more likely to produce a weight loss of ≥ 10% from baseline. Medication-induced weight loss plateaus ~6 months. Weight remains below baseline during active treatment with anorexiants for ≥ 2 years. Reported adverse effects, if any, are mild and self-limited; serious adverse events are rare. 50 6/21/2016 Long-Term Pharmacotherapy in the Management of Obesity Position Statement: “Pharmacotherapy, when combined with appropriate dietary change and physical activity, helps some obese and overweight patients lose more weight and maintain the weight loss better than with dietary, activity and behavioral modifications alone.” National Task Force on the Prevention and Treatment of Obesity. JAMA 276(23): 1907-15 (Dec 1996). Qsymia® ©IV (Low-dose Phentermine + Topiramate ER) FDA-approved in 2012 for chronic therapy as an adjunct to diet and exercise in patients with: Obesity: BMI over 30 kg/m² Overweight: BMI over 27 kg/m² plus at least one weight-related co-morbidity (hypertension, diabetes type II, hyperlipidemia, etc) ______________________________________________________________________________ Qsymia is available in 4 fixed-ratio combinations: Phentermine (mg) 3.75 Topiramate ER (mg) 23 7.5 46 11.25 69 15 92 Can be Rx’ed by PA’s / CRNP’s in Alabama (2015). 51 6/21/2016 Phentermine/Topiramate ER combination (SEQUEL trial) Mean (95% CI) percentage weight loss from baseline to week 108. ©2012 by American Society for Nutrition Garvey W T et al. Am J Clin Nutr 2011;95:297-308 Qsymia® Adverse Effects Pregnancy category X (cleft lip, palate, et.al.). Both phentermine and topiramate cross blood-milk barrier, so do not take if breast-feeding. Topiramate causes metabolic acidosis: Paresthesias in the face, lips, hands and feet Increases the risk of forming renal stones Impaired memory, concentration, speech Phentermine may cause anxiety, panic, aggression Most common were anticholinergic effects (dry mouth, dry eyes, constipation), sinus infections, and URI’s. REMS is available from the manufacturer, VIVUS. 52 6/21/2016 Belviq® (lorcaserin) Belviq® FDA-approved in 2012 for chronic therapy ► Obesity: BMI over 30 kg/m² ► Overweight: BMI over 27 kg/m² plus at least one weight-related co-morbidity (eg, HTN, DM, Lipids) _________________________________________________________________________________________________________ Available as 10 mg film-coated tablet. Recommended to begin with 10 mg once daily for up to 2 weeks. An increase to 10 mg BID yields better weight reduction and maintenance at one year. Eisai provides REMS. _________________________________________________________________________________________________________ Potential adverse effects (mostly serotonergic): Headache, dizziness, fatigue, nausea, constipation, dry mouth Low blood sugar Bradycardia Hallucinations Inattention, memory impairment Serotonin syndrome Neuroleptic malignant syndrome Painful erections Reduction in RBC or WBC counts Belviq® (lorcaserin) ► Selectively activates 5-HT2C receptors in the brain ► Increases the production of Hypothalamic POMC (pro-opiomelanocortin), leads to earlier satiety ► Has both serotonergic and anorectic properties Arena: Patients must lose 5% of TBW in 12 weeks to continue. 53 6/21/2016 Contrave® (naltrexone/buproprion) Contrave® FDA-approved in 2014 chronic therapy: ► Obesity: BMI over 30 kg/m² ► Overweight: BMI over 27 kg/m² plus 1+ weightrelated co-morbidity (eg, HTN, DM-2, hyperlipidemia) ► Available as a single fixed-dose combination: Naltrexone (mg) 8 mg In bottles of Buproprion ER (mg) 90 mg 120 tablets Sites of action: hypothalamus and mesial limbic system, leading to regulation of appetite, intake and satiety. Contrave® clinical studies used two tablets BID. Risks include seizure, nausea, headache, constipation, hepatotoxicity, hypertension, tachycardia, suicidal thoughts and behaviors, mania, or opiate withdrawal. Prescription only, non-controlled, no DEA scheduling. Saxenda® (liraglutide injection) Saxenda® FDA-approved in 2014 chronic therapy: ► Obesity: BMI over 30 kg/m² ► Overweight: BMI over 27 kg/m² plus at least one weight-related co-morbidity (eg, HTN, DM, Lipids) Weekly subcutaneous injection, with dosing determined by an escalating schedule: Mode of action: Agonist of the Glucagon-like-peptide-1 receptor: Stimulates insulin secretion and sensitivity in α-cells and β-cells; inhibits gastric acid secretion and gastric motility; decreases food intake by aiding brain satiety. Adverse effects and risks include nausea, tachycardia at rest, pancreatitis, gallstones, hypertriglyceridemia, thyroid tumors and medullary cancer, hypoglycemia, renal failure, depression. Non-controlled, no DEA regulation. Tread very carefully. 54 6/21/2016 XI. Alabama Board of Medical Examiners RULES FOR PRESCRIBING ANOREXIANTS Alabama Board of Medical Examiners Rules for the Prescribing of Anorexiants 540-X-17 written by an ad hoc committee of two ABME Members and several weight-loss physicians In Effect since January, 2012 55 6/21/2016 The evaluation before prescribing: 1) The prescribing physician (MD,DO) will take and document an appropriate medical history (illnesses, medications, surgeries, dietary, exercise) and perform a physical examination; 2) Obtain ancillary testing (labs, cardiac, urine) based on the history and physical, when medically indicated for weight management; 3) Discuss with the patient the risks, benefits and relative contraindications to anorexiants; 4) Assess freedom from drug or alcohol abuse; 5) Make medical referrals when indicated. DEA Scheduled Class II medications are NOT to be prescribed or dispensed in Alabama for the treatment of obesity, weight reduction or weight control. Such drugs include d-amphetamine (Dexedrine®), methamphetamine (Desoxyn®, Hydrin®), and any other Schedule II sympathomimetics (Adderall®, Ritalin®, Concerta®, ProCentra®), or any preparations that are equivalent to Class II stimulants. [ This position on Class II drugs is endorsed by the Obesity Medicine Association. ] Vyvanse® ©II, is FDA-approved for binge-eating disorder, a diagnosis distinctly different from exogenous obesity. 56 6/21/2016 In Alabama, prescribing or dispensing of the older Class III-IV anorexiants that are not FDA-approved for chronic use (phentermine, phendimetrazine, benzphetamine, diethylproprion) is limited to: Doctors of Medicine (MD’s) and Doctors of Osteopathy (DO’s), that hold: A valid medical license (Medical Licensure Commission); An Alabama Controlled Substances Certificate (ABME). Prescribing of the newer Class IV drugs that are FDA-approved for chronic use (Qsymia® and Belviq®) is open to all prescribers: PA’s, CRNP’s, MD’s, DO’s. These two drugs are FDA-approved for long-term use, unlike the older drugs that are prescribed off-label. Contrave® and Saxenda® are not Scheduled by DEA. Patient criteria to qualify for treatment with Scheduled Class III, IV, V anorexiants: Obesity (BMI of 30 or above) - OR Overweight (BMI of 25.0-29.9) with at least one weight-related comorbidity factor - OR FEMALES MALES Abdominal girth ≥ 35 inches ≥ 40 inches - OR Body fat content ≥ 30 % ≥ 25 % 57 6/21/2016 A prescribing physician (MD/DO) must be present in the clinic at the time any Class III, IV, or V anorexiant is prescribed or dispensed. A written prescription for any of the older (1959-60) Schedule III or IV anorexiants for the purpose of weight reduction or weight maintenance must be signed by a doctor (MD or DO) on the date the prescription is provided to a patient, or that a medication is dispensed in a clinic. Prescribing or dispensing an anorexiant is limited to a maximum supply of 35 days at a time. Each patient must be re-evaluated in person every 35 days by an MD/DO, or a PA/CRNP working in collaboration with an on-premises physician. Maintain appropriate medical records (weight, BMI, BP, HR, labs / tests) during anorexiant therapy. Carefully document the presence or absence of any adverse effects of anorexiant therapy. PA’s and CRNP’s may write and sign prescriptions for Qsymia® or Belviq®, if their collaborative doctor is physically present in the clinic. PA’s and CRNP’s may write and sign prescriptions for Contrave® or Saxenda® with or without the presence of a doctor, as these drugs are not scheduled by the DEA or the ABME. Physicians will follow all the applicable laws and rules for transmission of electronic prescriptions. NO phone, fax or email prescriptions are allowed. Refills are allowed ONLY for Qsymia®, Belviq®, Contrave® or Saxenda®, up to 6 months per visit. 58 6/21/2016 Within the first 70 days of Schedule III-IV anorexiant therapy, the treated patient should show progress toward established medical goals* (* loss of weight, body fat reduction, lower W:H ratio, smaller abdominal girth, improved diabetes control, hypertension control, or improvement in serum lipids, gastric reflux, LBP, musculoskeletal symptoms, etc.) Once the established medical goals* have been met, the MD/DO should prescribe reduced dosing and/or utilize drug holidays for those patients needing to continue on maintenance medication. Longer-term therapy is permissible by ABME Rules … but is still considered off-label by FDA/DEA. All patients should be appropriately advised of the off-label nature of longer-term anorexiant therapy, with signed informed consent. SITUATIONS LEADING TO TERMINATION OF ANOREXIANT Pregnancy - or breast-feeding Substance abuse - history of drug or alcohol abuse or a propensity toward such abuse Dishonesty - making false or misleading statements to the prescribing doctor, PA, CRNP or office staff Diversion - selling or improper consumption Noncompliance - repeatedly failing to comply with the prescriber’s treatment recommendations, including dietary and exercise instructions Lack of progress - development of tolerance to the clinical effects of the medication being used 59 6/21/2016 ABME Rule Related to hCG hCG (human chorionic gonadotrophin) Injectable hCG is FDA-approved for female infertility. NO products (shots, pellets, drops, sprays) alleging hCG content are FDA-approved for weight loss. Persons who purchase these products are given a 500-calorie ketotic diet. NO evidence exists that oral hCG products aid weight loss, beyond that of the ketosis from the very low calorie diet. The FDA and FTC (on 12-06-11) issued warnings to seven companies marketing over-the-counter hCG products labeled as “homeopathic” for weight loss, warning those companies that they are in violation of federal laws by selling drugs that have not been FDA-approved and that their actions are fraudulent and illegal in the USA. The ABME Rules prohibit all Alabama practitioners from selling or promoting any oral “hCG” products for weight loss. ABME Rules Related to the Prescribing of Anorexiants Practice evidence-based medicine! One example of evidence-based medicine in reference to obesity management is the set of “Practice Guidelines” published by the Obesity Medicine Association (and referenced in the ABME Rules) www.obesitymedicine.org 60 6/21/2016 XII. ANOREXIANTS LIMITATIONS TO TREATMENT Anorexiant Concerns Obese/Overweight Type II Diabetes Patients Obese/Overweight Hypertension Patients Obese/Overweight Coronary Artery Disease Patients Obese/Overweight Cardiac Dysrhythmia Patients Obese/Overweight Migraine/Headache Patients Obese/Overweight Depressed Patients Obese/Overweight Anxiety Disorder Patients Obese/Overweight Bipolar Disorders Patients Obese/Overweight Adult Patients Treated with Medications for Attention Deficit Disorder Obese/Overweight Patients of Advancing Age 61 6/21/2016 Obese/Overweight Diabetic-II Patients Anorexiants are very useful in aiding obese or overweight adults with type II diabetes lose weight more readily. Once a type II diabetic patient begins an anorexiant, the serum glucose drops rapidly within the first few days. To help prevent inadvertent hypoglycemia, and because all insulins cause weight gain, I instruct patients to reduce the insulin dose by 1/3 on day one of anorexiant therapy. Weight, waist and glucose all decrease more rapidly with the reduced insulin dose. Patients on oral agents should check glucose BID for a couple of weeks. Metformin (Glucophage®, etc.) and all the SGLT-2 inhibitors often result in weight loss in type II diabetic patients. These may be preferable over other oral agents associated with weight gain. Also, some of the newer noninsulin injectable drugs (Byetta®, etc.) may be associated with weight loss. Patients with Hypertension If initial blood pressure > 140/90: Initiate antihypertensive therapy at the same time as prescribing an anorexiant, and stress the importance of taking them together. I generally start with a potassiumsparing diuretic (Maxzide or Dyazide) esp if edema is present; lisinopril 5-20 mg if heart rate is normal; or atenolol or metoprolol 25-50 mg if both the blood pressure and heart rate are elevated. If initial blood pressure > 152/96: Treat with antihypertensive therapy for 1-2 weeks, then recheck BP prior to prescribing an anorexiant. 62 6/21/2016 Patients with Coronary Artery Disease Although unpublished and somewhat arbitrary, I tend to use a “2-year rule” when treating cardiac patients with any of the adrenergic/noradrenergic anorexiants: 2 years since CABG 2 years since insertion of a stent 2 years since cardiac catheterization (if abnormal) Among the “older” anorexiants, Tenuate (diethylproprion) has a primarily dopaminergic effect and is safest among patients with coronary, cardiac or hypertensive disease. Weight reduction (in particular, abdominal fat reduction) helps cardiac patients live longer and healthier, and anorexiant benefit may outweigh risks within parameters. Patients with a Cardiac Dysrhythmia Cardiac risks clearly exceed weight loss benefits in certain situations, therefore Do Not Use Anorexiants in: • • • • • Wolff-Parkinson-White Syndrome Left Bundle Branch Block (LBBB), new Recent onset Atrial Fibrillation Chronic A-Fibrillation with RVR (>95 bpm) QTc prolongation > 0.44 sec 63 6/21/2016 Obese/Overweight Migraine Patients Both headache and obesity are common in the population, and often occur together. Although headache is listed in PDR as a potential adverse effect of anorexiants (and patients should be so warned), they rarely report a significant increase in headache frequency, severity or duration with anorexiant Rx. Topamax® (topiramate) is FDA-approved for migraine prevention, and is commonly associated with weight loss. Zonegran® (zonisamide) is used off-label for migraine prevention and is sometimes associated with weight loss. Keppra® (levetiracetam) is used off-label for migraine prevention and is weight-neutral or with small weight loss. Depakote® (valproate) is FDA-approved for prevention of migraine. Significant weight gain is very common problem with this drug, among numerous other adverse effects. Obese/Overweight Depressed Patients Phentermine when taken in conjunction with: Total <3 mo 3-6 mo >6 mo Prozac 581 209 109 263 Zoloft 111 21 28 62 Celexa 73 20 15 38 Lexapro 69 17 15 37 Paxil 13 2 5 6 Tricyclics 159 25 39 95 ~ CASES OF SEROTONIN SYNDROME: ZERO (0) ~ Tricyclic (TCA) antidepressants are virtually always associated with weight gain, dry mouth, dry eyes and constipation. Also, TCA’s bear a risk for arrhythmias. Concomitant use of a TCA with an anorexiant is an open invitation for adverse effects. 64 6/21/2016 Patients with Anxiety Disorders Persons with anxiety disorders commonly overeat, or choose fattening foods, as “treatment” during periods of anxiety. SSRI’s are widely prescribed for treatment of anxiety and panic disorder. Weight gain may be significant with these drugs, with Paxil (paroxetine) and Zoloft (sertraline) at the top of the list and Luvox (fluvoxamine) and Lexapro (escitalopram) being less associated with weight gain. Prozac (fluoxetine) is more commonly associated with weight loss than weight gain. The NRI Wellbutrin (buproprion) often aids weight loss. The SNRI’s Effexor (venlafaxine) and Pristiq (desvenlafaxine) may cause weight gain at lower doses, but are weight-neutral at higher doses due to increased norepinephrine effect. For anorexiant-induced anxiety in otherwise responding patients, a low dose of a mild anxiolytic aids tolerability of the drug. Patients with Bipolar Disorders Unfortunately, most of the medications used in the treatment of bipolar disorders are associated with or cause weight gain, Depakote® (valproate) and Lithium in particular. Avoid anorexiants in bipolar patients due to the high risks of CNS excitability, and the high potential for production of mania/hypomania. The risks far exceed any potential benefit of anorexiants in this group (!). 65 6/21/2016 Obese/Overweight Persons Treated with Medications for Attention Deficit Disorder or Other Schedule II Drugs Do Not Prescribe an Anorexiant until a person has been off a Schedule II ADD or ADHD medication for a period of at least six (6) weeks. Use the PDMP and appropriate drug testing to confirm the absence of other amphetamine-like drugs prior to prescribing. Obese/Overweight in Advancing Age Most individuals actually lose, not gain, weight as they age. Patients over 65 years of age presenting to a weight loss specialist usually do so in order to improve control of diabetes type II. Be aware that older individuals: 1) are usually already taking several daily medications; 2) have a greater potential for adverse effects of anorexiants (dry mouth, dry eyes, constipation, hypertension, glaucoma, arrhythmias, insomnia, etc.); 3) have a greater risk of drug-drug interactions between their daily medications and anorexiants. Always weigh the potential risks vs. benefits of any drug (anorexiants included) and discuss these potential risks and benefits in detail prior to prescribing. Best to have a recent EKG on the chart, and “go low and go slow.” 66 6/21/2016 Robert F. Allen, MD Weight Management Clinic 105 N. Pontiac Ave, Suite 1 Dothan, AL 36303-3959 rfa7255 @ hotmail.com 67