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Management of the Morbidly Obese Sarah Nelson, Pharm.D.  Pharmacy Practice Resident
Objectives <ul><li>Describe the proposed origins of obesity </li></ul><ul><li>Discriminate between current treatment optio...
Definition of Obesity <ul><li>An imbalance between energy intake and energy expenditure </li></ul><ul><li>Consumption of c...
Classification of Body Weight Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analy...
Background <ul><li>Obesity recognized as a marker for mortality in the 1960’s </li></ul><ul><ul><li>Analysis of life insur...
Prevalence of Weight Disorders <ul><li>1.6 billion individuals are overweight </li></ul><ul><ul><li>Highest in United Stat...
Effects of Weight Disorders <ul><li>Major cause of preventable death </li></ul><ul><ul><li>>100,000 deaths per year </li><...
In a Decade . . .  http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm
Effects of Obesity <ul><li>Increase in prevalence of co-morbidities </li></ul><ul><ul><li>Diabetes Mellitus Type 2 </li></...
Obesity and Diabetes <ul><li>Increase in circulating free fatty acids competes with circulating glucose    elevated insul...
Origins of Obesity
Origins of Obesity <ul><li>Genetic </li></ul><ul><li>Environmental/Behavioral </li></ul>
Regulation of Energy Balance Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
Genetic Effects <ul><li>Gene deletions/mutations </li></ul><ul><ul><li>Leptin deficiency/leptin receptor modification </li...
Genetic Effects <ul><li>Syndromic association  </li></ul><ul><ul><li>>20 syndromes caused by genetic defects or chromosome...
Genetic Effects <ul><li>Genetics of common obesity </li></ul><ul><ul><li>1977 NHLBI Twin Study    familial obesity due to...
Environmental <ul><li>Location </li></ul><ul><ul><li>Access to walk paths, recreational facilities, etc. </li></ul></ul><u...
Environmental <ul><li>Results from the Ontario Heart Health Surveys (OHHS) demonstrate an increase in obesity with: </li><...
Treatment Options for Obesity
Treatment Options for Obesity <ul><li>Diet Therapy </li></ul><ul><li>Pharmaceutical Agents </li></ul><ul><ul><li>Sibutrami...
Sibutramine (Meridia ® ) <ul><li>MOA: inhibits norepinephrine (NE) and serotonin (5-HT 2 ) neuronal uptake    enhances sa...
Sibutramine (Meridia ® ) <ul><li>Bray et al. (1999) </li></ul>Bray G, Blackburn G, Ferguson J et al. Sibutramine produces ...
STORM Trial <ul><li>Randomized, double-blind, placebo controlled trial </li></ul><ul><li>Effect of weight maintenance afte...
STORM Trial James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight  loss: a randomise...
Sibutramine (Meridia ® )   <ul><li>Use with caution in patients on concurrent serotonergic medications </li></ul><ul><ul><...
Bupropion <ul><li>MOA: inhibits NE and DA neuronal uptake    enhances satiety </li></ul><ul><li>Dose: 300 to 400 mg daily...
Bupropion <ul><li>Anderson et al. (2002) </li></ul><ul><li>24 week RDBPC parallel-group study </li></ul><ul><li>Compared p...
Bupropion Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-co...
Orlistat (Alli ® , Xenical ® ) <ul><li>MOA: reversible inhibitor of gastric and pancreatic lipases    decreases dietary f...
<ul><li>Davidson et al. (1999) </li></ul><ul><li>2-year DBRPC study </li></ul><ul><li>Diet modified to ensure adequate fat...
Orlistat (Alli®, Xenical®) Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese s...
<ul><li>Concerns with orlistat: </li></ul><ul><ul><li>  in fat-soluble vitamin deficiency </li></ul></ul><ul><ul><li>Gast...
Other Medications <ul><li>Metformin </li></ul><ul><ul><li>1700 mg daily    300 kcal intake reduction/30-minute eating per...
Future Pharmacologic Agents <ul><li>Recombinant human leptin </li></ul><ul><li>Neuropeptide Y antagonists </li></ul><ul><l...
Rimonabant <ul><li>MOA: CB 1  receptor antagonist </li></ul><ul><li>Dose: 20 mg daily </li></ul><ul><li>Adverse Effects: s...
RIO Trials <ul><li>Efficacy </li></ul><ul><ul><li>Decreased body weight (-6.6 kg) </li></ul></ul><ul><ul><li>Decreased wai...
Leptin <ul><li>Peptide that acts on the hypothalamus to modulate body weight, intake and fat stores </li></ul><ul><li>Lept...
Bariatric Surgery <ul><li>Only option for treatment of morbidly obese </li></ul><ul><li>20-fold increase in procedures in ...
Gastric Bypass <ul><li>Restrictive and malabsorptive </li></ul><ul><ul><li>Causes early satiety and incomplete nutrient di...
Gastric Bypass <ul><li>Complications </li></ul><ul><ul><li>Mortality rate: 0.5% </li></ul></ul><ul><ul><li>Early complicat...
Gastric Banding <ul><li>Restrictive procedure </li></ul><ul><li>Implantation of inflatable silicone band around the upper ...
Gastric Banding <ul><li>Complications </li></ul><ul><ul><li>Safest bariatric procedure available  </li></ul></ul><ul><ul><...
Banding vs. Bypass Tice J, Karliner L, Walsh J et al. Gastric banding or bypass? A systematic review comparing  the two mo...
Biliopancreatic diversion <ul><li>Restrictive and malabsorptive properties </li></ul><ul><ul><li>Limited gastrectomy </li>...
Complications of Bariatric Surgery <ul><li>Unexpected reoperation </li></ul><ul><ul><li>Wound dehiscence </li></ul></ul><u...
Short Bowel Syndrome (SBS) <ul><li>Definition: intestinal remnant <180 cm AND malabsorption </li></ul><ul><li>Complication...
Outcomes in the Bariatric Patient
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Fi...
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Fi...
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Fi...
Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Fi...
Results from Bariatric Surgery <ul><li>Co-morbidities resolve as weight  ↓ </li></ul><ul><li>Hospitalization rate increase...
In the mean time . . .
Dosing Controversies in Obesity <ul><li>Weight  </li></ul><ul><ul><li>IBW vs. ABW vs. Adjusted body weight </li></ul></ul>...
Conclusions <ul><li>Obesity is becoming more prevalent </li></ul><ul><li>Genetic make-up may predispose pts to obesity </l...
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Management Of The Morbidly Obese

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Management Of The Morbidly Obese

  1. 1. Management of the Morbidly Obese Sarah Nelson, Pharm.D. Pharmacy Practice Resident
  2. 2. Objectives <ul><li>Describe the proposed origins of obesity </li></ul><ul><li>Discriminate between current treatment options for obesity </li></ul><ul><li>Examine the effects following bariatric surgery </li></ul><ul><li>Distinguish dynamic and kinetic differences in obese patients </li></ul>
  3. 3. Definition of Obesity <ul><li>An imbalance between energy intake and energy expenditure </li></ul><ul><li>Consumption of calories which exceeds that required for the resting metabolic rate and active energy expenditure </li></ul><ul><li>Energy equation: </li></ul><ul><ul><li>Intake (food) = expenditure + storage </li></ul></ul>Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.
  4. 4. Classification of Body Weight Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737 Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6 th edition. 63-81. Class III Obesity ≥ 40 Class II Obesity 35.0-39.9 Class I Obesity 30.0-34.9 Overweight 25.0-29.9 Normal weight 18.5-24.9 Underweight <18.5 Weight Category BMI (kg/m 2 )
  5. 5. Background <ul><li>Obesity recognized as a marker for mortality in the 1960’s </li></ul><ul><ul><li>Analysis of life insurance redemption </li></ul></ul><ul><ul><ul><li>Mortality lowest when BMI 20-25 </li></ul></ul></ul><ul><ul><ul><li>Mortality dramatically increased when BMI >35 </li></ul></ul></ul><ul><ul><ul><li>Mortality also increased when BMI <20 </li></ul></ul></ul><ul><li>In 2000, WHO declared obesity as the greatest health threat facing the West </li></ul>Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S.
  6. 6. Prevalence of Weight Disorders <ul><li>1.6 billion individuals are overweight </li></ul><ul><ul><li>Highest in United States </li></ul></ul><ul><li>2 out of 3 Americans are overweight </li></ul><ul><ul><li>½ of all overweight Americans are obese </li></ul></ul><ul><ul><li>BMI ≥ 35 kg/m 2 : 23 million Americans </li></ul></ul><ul><ul><li>BMI ≥ 40 kg/m 2 : 8 million Americans </li></ul></ul>Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737
  7. 7. Effects of Weight Disorders <ul><li>Major cause of preventable death </li></ul><ul><ul><li>>100,000 deaths per year </li></ul></ul><ul><ul><li>$70 billion health care dollars per year </li></ul></ul><ul><ul><li>10% of national healthcare expenditure </li></ul></ul>Pieracci F, Barie P, Pomp A. Critical care of the bariatric patient. Crit Care Med. 2006;34: 1796-1804
  8. 8. In a Decade . . . http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm
  9. 9. Effects of Obesity <ul><li>Increase in prevalence of co-morbidities </li></ul><ul><ul><li>Diabetes Mellitus Type 2 </li></ul></ul><ul><ul><li>Heart Disease (HTN, XOL, stroke) </li></ul></ul><ul><ul><li>Obstructive sleep apnea </li></ul></ul><ul><ul><li>Weight-bearing degenerative disorders </li></ul></ul><ul><ul><li>Depression </li></ul></ul><ul><ul><li>Cancer </li></ul></ul><ul><li>Decreased life expectancy </li></ul>Buchwald H, Avidor Y, Braunwald et al. Bariatric Surgery: A Systematic Review and Meta-analysis. JAMA 2004. 292: 1724-1737
  10. 10. Obesity and Diabetes <ul><li>Increase in circulating free fatty acids competes with circulating glucose  elevated insulin secretion and resistance </li></ul><ul><li>Resistin, adiponectin, and TNF- α interact with insulin to generate insulin resistance </li></ul>Speakman, J. Obesity: the integrated roles of environment and genetics. J Nutr. 2004;134: 2090S-2105S. http://www.nature.com/nrm/journal/v9/n5/images/nrm2391-f2.jpg
  11. 11. Origins of Obesity
  12. 12. Origins of Obesity <ul><li>Genetic </li></ul><ul><li>Environmental/Behavioral </li></ul>
  13. 13. Regulation of Energy Balance Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
  14. 14. Genetic Effects <ul><li>Gene deletions/mutations </li></ul><ul><ul><li>Leptin deficiency/leptin receptor modification </li></ul></ul><ul><ul><li>MC4R deficiency </li></ul></ul><ul><ul><ul><li>Most common monogenic disorder to date </li></ul></ul></ul><ul><ul><ul><li>Present in 1-6% of obese individuals </li></ul></ul></ul><ul><ul><li>GAD65 over-expression </li></ul></ul><ul><ul><ul><li>Increases production of GABA  increased food intake </li></ul></ul></ul>Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
  15. 15. Genetic Effects <ul><li>Syndromic association </li></ul><ul><ul><li>>20 syndromes caused by genetic defects or chromosome abnormalities are characterized by obesity </li></ul></ul><ul><ul><ul><li>Most are in the setting of mental retardation </li></ul></ul></ul><ul><ul><ul><li>Prader-Willi syndrome </li></ul></ul></ul><ul><ul><ul><li>Pseudohypoparathyroidism type 1A </li></ul></ul></ul><ul><ul><ul><li>Bardet-Biedl syndrome </li></ul></ul></ul>Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29.
  16. 16. Genetic Effects <ul><li>Genetics of common obesity </li></ul><ul><ul><li>1977 NHLBI Twin Study  familial obesity due to genetic factors rather than environment </li></ul></ul><ul><ul><ul><li>Estimated heritability value of 0.81 upon 25 year follow up </li></ul></ul></ul><ul><ul><li>Adoption Studies </li></ul></ul><ul><ul><ul><li>Adopted children have body sizes more similar to biologic parents rather than adopted parents </li></ul></ul></ul>Bell C, Walley A, Froguel, P. The genetics of human obesity. Nature Reviews. 2005;6:221-29. Stunkard A, Sorenson T, Hanis C, et al. An adoption study of human obesity. JAMA. 1986;314:193-198.
  17. 17. Environmental <ul><li>Location </li></ul><ul><ul><li>Access to walk paths, recreational facilities, etc. </li></ul></ul><ul><ul><li>Access to fast food restaurants, supermarkets, health-related stores </li></ul></ul><ul><li>Socioeconomic status (SES) </li></ul><ul><ul><li>Inverse relationship between individual and area-level SES and weight </li></ul></ul>Harrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.
  18. 18. Environmental <ul><li>Results from the Ontario Heart Health Surveys (OHHS) demonstrate an increase in obesity with: </li></ul><ul><ul><li>Increased age (females>males) </li></ul></ul><ul><ul><li>Absence of high school education </li></ul></ul><ul><ul><li>Adoption of a sedentary lifestyle </li></ul></ul><ul><li>Nicotine consumption was a negative risk factor for obesity in the OHHS population </li></ul>Harrington D, Elliott S. Weighing the importance of a neighborhood: a multilevel exploration of the determinants of overweight and obesity. Social Science & Medicine. 2009;68:593-600.
  19. 19. Treatment Options for Obesity
  20. 20. Treatment Options for Obesity <ul><li>Diet Therapy </li></ul><ul><li>Pharmaceutical Agents </li></ul><ul><ul><li>Sibutramine </li></ul></ul><ul><ul><li>Orlistat </li></ul></ul><ul><ul><li>Bupropion </li></ul></ul><ul><ul><li>Potential targets </li></ul></ul><ul><li>Surgical Therapy </li></ul><ul><ul><li>Gastric Banding </li></ul></ul><ul><ul><li>Gastric Bypass </li></ul></ul><ul><ul><li>Biliopancreatic diversion </li></ul></ul>
  21. 21. Sibutramine (Meridia ® ) <ul><li>MOA: inhibits norepinephrine (NE) and serotonin (5-HT 2 ) neuronal uptake  enhances satiety </li></ul><ul><li>Dose: 10 mg PO once daily x 4 wks, then may  to 15 mg daily x 100 wks </li></ul><ul><li>Adverse Effects (>10%) </li></ul><ul><ul><li>Headache </li></ul></ul><ul><ul><li>Insomnia </li></ul></ul><ul><ul><li>Xerostomia </li></ul></ul><ul><ul><li>Constipation </li></ul></ul>Chaput JP, Tremblay A. Current and novel approaches to the drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.
  22. 22. Sibutramine (Meridia ® ) <ul><li>Bray et al. (1999) </li></ul>Bray G, Blackburn G, Ferguson J et al. Sibutramine produces dose-related weight loss. Obes Res. 1999;7:189-98 . 46.5* 77.2* 9.0 30 101 36.5* 71.9* 8.2 20 96 34.7* 67.3* 7.0 15 98 17.2* 59.6* 5.7 10 99 12.1* 37.4 Ұ 3.7 5 107 10.5 Ұ 25.3 2.4 1 95 0 19.5 1.3 Placebo 87 >10% wt loss (%) >5% wt loss (%) Mean wt reduction (kg) Dose (mg) n
  23. 23. STORM Trial <ul><li>Randomized, double-blind, placebo controlled trial </li></ul><ul><li>Effect of weight maintenance after weight loss </li></ul><ul><li>All patients on a 600 kcal/day deficit diet </li></ul>James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.
  24. 24. STORM Trial James W, Astryp A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356:2119-25.
  25. 25. Sibutramine (Meridia ® ) <ul><li>Use with caution in patients on concurrent serotonergic medications </li></ul><ul><ul><li> risk of serotonin syndrome </li></ul></ul><ul><ul><li>Previous black box warning </li></ul></ul><ul><li>Use with caution in patients with uncontrolled hypertension </li></ul><ul><ul><li>12.5% patients   in BP by 15 mmHg </li></ul></ul>Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  26. 26. Bupropion <ul><li>MOA: inhibits NE and DA neuronal uptake  enhances satiety </li></ul><ul><li>Dose: 300 to 400 mg daily </li></ul><ul><li>Non-FDA approved indication </li></ul><ul><li>Contraindicated in patients with seizure disorders </li></ul>Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
  27. 27. Bupropion <ul><li>Anderson et al. (2002) </li></ul><ul><li>24 week RDBPC parallel-group study </li></ul><ul><li>Compared placebo, 300 mg, & 400 mg daily </li></ul><ul><li>Calorie restricted diet & lifestyle intervention program initiated </li></ul>Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
  28. 28. Bupropion Anderson J, Greenway F, Fujioka K, et. al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obesity Research. 2002;10:633-41.
  29. 29. Orlistat (Alli ® , Xenical ® ) <ul><li>MOA: reversible inhibitor of gastric and pancreatic lipases  decreases dietary fat absorption </li></ul><ul><li>Only FDA approved drug that directly alters metabolism </li></ul><ul><li>Dose: 120 mg TID with meals </li></ul>
  30. 30. <ul><li>Davidson et al. (1999) </li></ul><ul><li>2-year DBRPC study </li></ul><ul><li>Diet modified to ensure adequate fat intake </li></ul>Orlistat (Alli®, Xenical®) Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.
  31. 31. Orlistat (Alli®, Xenical®) Davidson M, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999;281:235-242.
  32. 32. <ul><li>Concerns with orlistat: </li></ul><ul><ul><li> in fat-soluble vitamin deficiency </li></ul></ul><ul><ul><li>Gastrointestinal adverse effects common </li></ul></ul><ul><ul><ul><li>Fatty/oily stool (20%) </li></ul></ul></ul><ul><ul><ul><li>Oily spotting (26.6%) </li></ul></ul></ul><ul><ul><ul><li>Fecal incontinence (7.7%) </li></ul></ul></ul><ul><ul><ul><li>Fecal urgency (22.1%) </li></ul></ul></ul><ul><ul><ul><li>Flatulence with discharge (23.9%) </li></ul></ul></ul>Orlistat (Alli®, Xenical®) Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  33. 33. Other Medications <ul><li>Metformin </li></ul><ul><ul><li>1700 mg daily  300 kcal intake reduction/30-minute eating period </li></ul></ul><ul><ul><li> hunger ratings </li></ul></ul><ul><li>Topiramate </li></ul><ul><ul><li>65.2% of patients had weight loss of 0.5 kg to 19.5 kg in migraine study </li></ul></ul><ul><ul><li>200 mg daily  average body weight  5.9 kg </li></ul></ul>Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  34. 34. Future Pharmacologic Agents <ul><li>Recombinant human leptin </li></ul><ul><li>Neuropeptide Y antagonists </li></ul><ul><li>GLP-1 </li></ul><ul><li>Ghrelin antagonists </li></ul><ul><li>Endocannabinoid receptor antagonists </li></ul>Schurgin S, Siegel R. Pharmacotherapy of obesity: an update. Nutrition in Clinical Care. 2003;6:27-37.
  35. 35. Rimonabant <ul><li>MOA: CB 1 receptor antagonist </li></ul><ul><li>Dose: 20 mg daily </li></ul><ul><li>Adverse Effects: suicidal ideation, anxiety, depression </li></ul><ul><li>Not available in US </li></ul><ul><ul><li>NDA withdrawn </li></ul></ul>
  36. 36. RIO Trials <ul><li>Efficacy </li></ul><ul><ul><li>Decreased body weight (-6.6 kg) </li></ul></ul><ul><ul><li>Decreased waist circumference (-3.9 cm) </li></ul></ul><ul><ul><li>Decreased BP (-1.8 mmHg SBP) </li></ul></ul><ul><ul><li>Decreased A1c (0.7%) </li></ul></ul><ul><ul><li>No decrease in LDL, total cholesterol </li></ul></ul><ul><li>Safety </li></ul><ul><ul><li>RR 1.9 for any psychiatric disorder </li></ul></ul><ul><ul><li>2.5x more likely to discontinue medication due to depression </li></ul></ul>Idelevich E, Kirch W, Schlinder C. Current pharmacotherapeutic concepts for the treatment of obesity in adults. Therapeutic Advances in Cardiovascular disease. 2009;3:75-90.
  37. 37. Leptin <ul><li>Peptide that acts on the hypothalamus to modulate body weight, intake and fat stores </li></ul><ul><li>Leptin deficiency  early onset obesity </li></ul><ul><li>Treatment options: </li></ul><ul><ul><li>Leptin analogues > native leptin </li></ul></ul><ul><ul><li>Leptin gene promoters </li></ul></ul><ul><li>CNTF may also potentiate leptin-like effects </li></ul>Chaput J, Tremblay A. Current and novel approaches to drug therapy of obesity. Eur J Clin Pharmacol. 2006;62:793-803.
  38. 38. Bariatric Surgery <ul><li>Only option for treatment of morbidly obese </li></ul><ul><li>20-fold increase in procedures in last 10 years </li></ul><ul><li>Types of surgery </li></ul><ul><ul><li>Restrictive </li></ul></ul><ul><ul><li>Malabsorptive </li></ul></ul><ul><ul><li>Combination </li></ul></ul>Steinbrook R. Surgery for severe obesity. NEJM. 2004;350:1075-79. Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200.
  39. 39. Gastric Bypass <ul><li>Restrictive and malabsorptive </li></ul><ul><ul><li>Causes early satiety and incomplete nutrient digestion and absorption </li></ul></ul><ul><li>Roux-en-Y surgery </li></ul><ul><ul><li>Creation of 15-30 cm gastric pouch </li></ul></ul><ul><ul><li>Connection of jejunum to gastric curvature </li></ul></ul><ul><ul><ul><li>Bypasses portion of stomach, duodenum, and portion of jejunum </li></ul></ul></ul><ul><li>Most common bariatric surgery </li></ul>Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  40. 40. Gastric Bypass <ul><li>Complications </li></ul><ul><ul><li>Mortality rate: 0.5% </li></ul></ul><ul><ul><li>Early complications: anastomotic leak, PE, infection </li></ul></ul><ul><ul><li>Late complications: strictures, bowel obstruction, malnutrition, dumping syndrome </li></ul></ul><ul><li>Outcomes </li></ul><ul><ul><li>62-68% excess weight loss at 2 years </li></ul></ul><ul><ul><ul><li>Initial weight loss of 70-80% excess weight </li></ul></ul></ul><ul><ul><ul><li>Regain of weight after 2 years is common </li></ul></ul></ul>Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  41. 41. Gastric Banding <ul><li>Restrictive procedure </li></ul><ul><li>Implantation of inflatable silicone band around the upper stomach </li></ul><ul><li>Band adjustments are based on individual weight loss and appetite </li></ul><ul><ul><li>Adjustments required 5-6 times in 1 st year </li></ul></ul>Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  42. 42. Gastric Banding <ul><li>Complications </li></ul><ul><ul><li>Safest bariatric procedure available </li></ul></ul><ul><ul><li>Mortality rate: 0.05-0.1% </li></ul></ul><ul><ul><li>Late complications: gastric prolapse, band erosion, port infection, tubing problems </li></ul></ul><ul><li>Outcomes </li></ul><ul><ul><li>Weight loss is gradual </li></ul></ul><ul><ul><li>57% excess weight loss after 6 years </li></ul></ul><ul><ul><ul><li>Direct correlation with motivation and follow-up </li></ul></ul></ul>Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Chan L, Downing J. Management of Patients Receiving Bariatric Surgery. Pharmacotherapy Self-Assessment Program, 6th edition. 63-81.
  43. 43. Banding vs. Bypass Tice J, Karliner L, Walsh J et al. Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures. The American Journal of Medicine. 2008;121:885-93. 14 17 Long term complication 3.3 5.2 Short term complication 75 84 Osteoarthritis 48 37 Dyslipidemia 66 56 Hypertension 72 77 Diabetes 64 34 Weight loss Gastric Bypass (n=232) Gastric Banding (n=160) Pt characteristic (%)
  44. 44. Biliopancreatic diversion <ul><li>Restrictive and malabsorptive properties </li></ul><ul><ul><li>Limited gastrectomy </li></ul></ul><ul><ul><li>Roux-en-Y reconstruction </li></ul></ul><ul><li>Patient still allowed to eat a full meal </li></ul><ul><li>Results similar initially to gastric bypass </li></ul><ul><ul><li>Continued malabsorption increases 2 nd year weight loss </li></ul></ul>Salameh J. Bariatric surgery: past and present. Am J Med Sci. 2006;331:194-200. Matrusso A, Roslin M, Kurian M et al. Bariatric surgery: an overview of obesity surgery. 2006;119:1357-62.
  45. 45. Complications of Bariatric Surgery <ul><li>Unexpected reoperation </li></ul><ul><ul><li>Wound dehiscence </li></ul></ul><ul><ul><li>Foreign body removal </li></ul></ul><ul><ul><li>laparotomy </li></ul></ul><ul><li>Splenic </li></ul><ul><ul><li>injury </li></ul></ul><ul><li>Hemorrhagic </li></ul><ul><ul><li>Intra-op hemorrhage </li></ul></ul><ul><ul><li>Post-op hematoma </li></ul></ul><ul><ul><li>Blood transfusion </li></ul></ul><ul><li>Anastomotic </li></ul><ul><ul><li>Leak </li></ul></ul><ul><ul><li>Abdominal drainage </li></ul></ul><ul><li>Wound </li></ul><ul><ul><li>Infection </li></ul></ul><ul><ul><li>Seroma </li></ul></ul><ul><ul><li>dehiscence </li></ul></ul><ul><li>Obstruction </li></ul><ul><ul><li>Small bowel obstruction </li></ul></ul>Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.
  46. 46. Short Bowel Syndrome (SBS) <ul><li>Definition: intestinal remnant <180 cm AND malabsorption </li></ul><ul><li>Complications necessitate small bowel resection </li></ul><ul><ul><li>Bowel obstruction </li></ul></ul><ul><ul><li>Internal hernias </li></ul></ul><ul><ul><li>Mesenteric thrombosis </li></ul></ul><ul><li>In a review of 265 pts with SBS </li></ul><ul><ul><li>15% due to bariatric surgery </li></ul></ul><ul><ul><ul><li>82% had Roux-en-Y gastric bypass </li></ul></ul></ul>McBride C, Petersen A, Sudan D. Short bowel syndrome following bariatric surgical procedures. American Journal of Surgery. 2006;192:828-32.
  47. 47. Outcomes in the Bariatric Patient
  48. 48. Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. -46.3 Biliopancreatic diversion -28.6 Gastric banding -43.5 Gastric bypass -8.6 Bupropion -7.6 Orilstat -10.2 Sibutramine Absolute weight change (kg) Treatment
  49. 49. Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. --- Biliopancreatic diversion --- Gastric banding --- Gastric bypass -1.73 Bupropion -0.8 Orilstat 0.1 Sibutramine Systolic BP (mmHg) Treatment
  50. 50. Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. -5.79 Biliopancreatic diversion -3.2 Gastric banding -3.4 Gastric bypass -2.71 Bupropion 1.0 Orilstat -0.8 Sibutramine Fasting glucose (mg/dL) Treatment
  51. 51. Co-morbidities following Treatment Buchwald H, Avidor Y, Braunwald E, et al. JAMA. 2004;292:1724-37. James W, Astryp A, Finer N, et al. Lancet. 2000;356:2119-25. Anderson J, Greenway F, Fujioka K, et. al. Obesity Research. 2002;10:633-41. Davidson M, Hauptman J, DiGirolamo M et al. JAMA. 1999;281:235-242. Biliopancreatic diversion Gastric banding Gastric bypass -2.95 Bupropion -20 Orilstat -0.8 Sibutramine LDL (mg/dL) Treatment
  52. 52. Results from Bariatric Surgery <ul><li>Co-morbidities resolve as weight ↓ </li></ul><ul><li>Hospitalization rate increases </li></ul><ul><ul><li>Band adjustments </li></ul></ul><ul><ul><li>Complications </li></ul></ul><ul><li>Complications exist </li></ul><ul><ul><li>Nutritional deficiencies </li></ul></ul><ul><ul><li>Medication absorption issues </li></ul></ul><ul><ul><li>Surgical complications </li></ul></ul><ul><ul><ul><li>Short bowel syndrome </li></ul></ul></ul>Santry H, Gillen D, Lauderdale D. Trends in bariatric surgical procedures. JAMA. 2005;294:1909-1917.
  53. 53. In the mean time . . .
  54. 54. Dosing Controversies in Obesity <ul><li>Weight </li></ul><ul><ul><li>IBW vs. ABW vs. Adjusted body weight </li></ul></ul><ul><li>Distribution </li></ul><ul><ul><li>Lipophilic vs. hydrophilic </li></ul></ul><ul><ul><li>Protein bound </li></ul></ul><ul><li>Clearance </li></ul><ul><li>Absorption </li></ul><ul><ul><li>Following bariatric surgery </li></ul></ul>Erstad B. Which weight for weight-based dosage regimens in obese patients? AJHP. 2002;59:2105-10.
  55. 55. Conclusions <ul><li>Obesity is becoming more prevalent </li></ul><ul><li>Genetic make-up may predispose pts to obesity </li></ul><ul><li>Pharmacological agents + diet are effective for overweight patients </li></ul><ul><li>Bariatric surgery is recommended for pts with BMI>35 </li></ul><ul><li>Bariatric surgery is most effective treatment for obesity </li></ul>

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