BARIATRIC SURGERY: A PHARMACY PERSPECTIVE

Hassan Hammoud, PharmD Candidate 2012Thomas Jefferson University

Preceptor: Sarah Nordbeck, PharmD, BCNSPNutrition Support Services

ObjectivesBy the end of this session, audience members will be

able to:

Explain the place in therapy of bariatric surgery Understand the anatomical and physiological changes

post bariatric surgery Describe nutrient deficiencies related to bariatric

surgery Recognize medication malabsorption issues as a result

of bariatric surgery Understand the role of a pharmacist post bariatric

surgery

Background – Obesity Obesity has reached

epidemic proportions globally (WHO) At least 2.6 million

deaths each year as a result of obesity

Was associated with high-income countries in the past now also prevalent in low/middle-income countries

Relation between mortality and BMI

Data from Lew, EA. Ann Intern Med 1985; 103:1024.

Background – Obesity Huge economic burden in the US (CDC)

Direct health costs attributable to obesity estimated at $52 billion in 1995 and $75 billion in 2003

Associated with many health risks Prevention is key Many approaches to treatment available

Dietary therapy, exercise, behavior modification, drug therapy, liposuction, surgery

Roux-en-Y Gastric BypassDescription

-Small pouch is created from a section of the stomach

-Section of stomach is attached directly to the small intestine

-Large part of the stomach and duodenum are bypassed

Rationale

-New stomach pouch is too small to hold large amounts of food

-Skipping the duodenum, fat absorption is substantially reduced

Image from: http://bakerbariatrics.com/procedure.htm#roux

Roux-en-Y Gastric Bypass

Image from: http://agajournals.files.wordpress.com/2011/09/ahima_bypass_figure.jpg

Pancreatic enzymes and bile acids come in contact with food at the Y-site

Bariatric Surgery – Indications Reserved for patients with a BMI >40 kg/m2

OR BMI >35 kg/m2 and 1 or more significant co-

morbid conditions When less invasive methods of weight loss have

failed and the patient is at high risk for obesity-associated morbidity and mortality

Pentin PL et. al. J Fam Pract. 2005;54:633.

Bariatric Surgery

Significant weight loss Improvement of co-

morbid conditions Resolution of Type II

Diabetes Improved

psychological function Improved QOL

Nutrient deficiencies

Protein malnutrition

Surgical complications

Dumping syndrome

Benefits Complications

Shikora SA, et al. Nutr Clin Pract. 2007;22(1):29-40.

IronFolic AcidCyanocobalaminThiamin

Part I – Nutrient Deficiencies

Sites of Nutrient Absorption - Stomach

Role in nutrient absorption Water Ethyl Alcohol Copper Iodide Fluoride Molybdenum Intrinsic Factor

Shikora SA, et al. Nutr Clin Pract. 2007;22(1):29-40. Image from : www.symptomsofstomachulcer.org

Sites of Absorption – Small Intestine

Calcium, Iron, Phosphorus, Magnesium, Copper, Selenium, Thiamin, Riboflavin

B-Vitamins, Vit C, Vit A, D, E,K, Ca, Phos, Mg, Zn, Iron, Chromium, Manganese,

Molybdenum, Amino Acids

Vit C, Folate, Vit B12, Vit D, Vit K, Magnesium, Bile salts/acids

Shikora SA, et al. Nutr Clin Pract. 2007;22(1):29-40.

Iron Mechanism of deficiency

Iron absorption is facilitated by gastric acid Predominantly absorbed in the duodenum and

proximal jejunum Secondary to the nutrient restriction

Manifestations Iron deficiency anemia

Prevention Multivitamin with iron and vitamin C

Treatment Ferrous sulfate 300 mg/d with vitamin C

Fe B12 B1B9

Heber D et al. J ClinEndocrinolMetab. 2010 ;95(11):4823-43

Cyanocobalamin Mechanism of deficiency

B12 absorbed in terminal ileum, but requires intrinsic factor

Intrinsic factor is produced in the parietal cells of stomach

Impaired formation of intrinsic factor-vitamin B12 complexes required for absorption

Manifestations Macrocytic anemia, megaloblastosis of the bone

marrow, leukopenia, thrombocytopenia, glossitis, or neurologic derangements

Ponsky TA, et al. J Am Coll Surg. 2005;201:125.

Fe B12 B1B9

Cyanocobalamin Prevention/Treatment

300-500 mcg PO Daily 1000 mcg IM monthly

Alternate option:1000 mcg IM initially, followed by 100-500mcg Q 2-4wks

500 mcg/wk nasal spray

Fe B12 B1B9

Ponsky TA, et al. J Am Coll Surg. 2005;201:125.Image from: www.empr.com/calomist/drugproduct/43/

Folic Acid Mechanism of deficiency

Vitamin B12 acts as a coenzyme in converting methyltetrahydrofolate to tetrahydrofolate

Folate absorption facilitated by HCl Occurs primarily in the upper one-third of the small intestine Restrictive diet post surgery drastic reduction in dietary folate

Manifestations Macrocytic anemia, leukopenia, thrombocytopenia, glossitis, or

megaloblastic marrow Prevention

Multivitamin with 1mg of folate Treatment

Folate 1 mg/d

Fe B12 B1B9

Ponsky TA, et al. J Am Coll Surg. 2005;201:125.

Thiamin Mechanism of deficiency

Thiamin preferably absorbed in the proximal portion of the small intestine

Loss of absorptive area leads to deficiency Restrictive diet post surgery drastic reduction in

dietary thiamin Manifestations

Wernicke’s encephalopathy Prevention

Multivitamin with thiamin Treatment

50 -100mg IV thiamin

Fe B12 B1B9

Decker GA et al. Am J Gastroenterol. 2007;102:2571.

Other Nutritional Deficiencies Amino acids Fat soluble vitamins (A,D,E & K) Calcium Zinc Magnesium Selenium

Heber D et al. J ClinEndocrinolMetab. 2010 ;95(11):4823-43

Monitoring Parameters Post Bariatric Surgery

Heber D et al. J ClinEndocrinolMetab. 2010 ;95(11):4823-43

Lipitor (Atorvastatin)Glucophage (Metformin)Zoloft (Sertraline)

Part II – Medication Malabsorption

Mechanisms of Medication Malabsorption

Surface area reduction for drug absorption

Decreased length of intestine and drug transit time

Changes in pH Drug dissolution in acidic vs. alkaline

environment Locations of drug transporters bypassed

Smith A et al. Am J Health Syst Pharm. 2011;68:2241.

Medication Strategies Drug Pharmacokinetics may be altered

due to anatomical change Selection of appropriate nutrient salts can

improve nutrient replacement Changes in dosage forms can improve

bioavailability Avoid extended release formulations Use liquid formulations if possible

Drug delivery systems that bypass GI absorption TD, IV, SL, nasal etc…

Lipitor® (Atorvastatin) Pharmacokinetic profile

Presystemic clearance via intestinal CYP 3A4 (low bioavailability 12%)

P-glycoprotein substrate Pharmacokinetic alteration post surgery

↑AUC, ↑Cmax, ↑tmax Mechanism of malabsorption

Intestinal CYP3A4 bypassed decreased presystemic metabolism increased bioavailability

Management Monitor lipids Monitor LFTs for toxicity Proper dose adjustment or use other agentsEdwards A, Ensom MH. Ann Pharmacother. 2012 ;46:130.

Glucophage® (Metformin) Pharmacokinetic profile

Absorption – slowly and incompletely absorbed in duodenum

Substrate for plasma membrane monoamine transporters Pharmacokinetic alteration post surgery

↑ bioavailability, ↑Vd Mechanism of malabsorption

Primary sites of absorption bypassed active transporters up-regulated leading to increased absorption

Management Increased monitoring of blood glucose recommended Drug requirements can decrease as weight loss occurs

Miller AD, Smith KM. Am J Health Syst Pharm. 2006;63:1852.Edwards A, Ensom MH. Ann Pharmacother. 2012;46:130.

Zoloft® (Sertraline) Pharmacokinetic profile

Metabolized by intestinal CYP3A4 Pharmacokinetic alteration post surgery

↓ AUC, ↓Cmax Mechanism of malabsorption

Loss of absorptive surface area greater impact vs. decreased presystemic metabolism

Management Close monitoring for psychiatric symptoms

Edwards A, Ensom MH. Ann Pharmacother. 2012;46:130.

Beaumont Practices Beaumont Bariatric Surgery Program

Began in 2001 Level 1 Accredited Bariatric Center (RO) certified by the American

College of Surgeons Number of surgeries annually

~300 at Beaumont >200,000 nationally

Multidisciplinary approach Surgeons, physicians, nurses, dieticians, psychiatrists & pharmacists

Post-surgery nutritional and exercise educational programs medical follow-up psychological counseling support groups cooking and nutrition classes

The Pharmacist’s Role/Clinical Pearls

Review patient’s medication regimen for appropriateness Check Prescribing Information for

medication use post bariatric surgery Recommend alternate routes of

administration Monitor for toxicity and therapeutic

efficacy Recommend appropriate nutritional

supplements Communicate closely with other

healthcare professionals

Conclusion Bariatric surgery is the most effective

treatment for long-term reduction of body weight

Nutritional and metabolic complications are likely after bariatric surgery Proper counseling, monitoring, and supplementation

become essential for prevention Drug Pharmacokinetics may be altered post

surgery Not predictable Close monitoring for efficacy/toxicity is necessary

Questions

References Heber D, Greenway FL, Kaplan LM, et al. Endocrine and nutritional management of the

post-bariatric surgery patient: an Endocrine Society Clinical Practice Guideline.J ClinEndocrinolMetab. 2010 Nov;95(11):4823-43.

Miller AD, Smith KM. Medication and nutrient administration considerations after bariatric surgery.Am J Health Syst Pharm. 2006 Oct 1;63(19):1852-7.

Smith A, Henriksen B, Cohen A. Pharmacokinetic considerations in Roux-en-Y gastric bypass patients.Am J Health Syst Pharm. 2011 Dec 1;68(23):2241-7

Malone M. Recommended nutritional supplements for bariatric surgery patients. Ann Pharmacother. 2008 Dec;42(12):1851-8. Epub 2008 Nov 18.

Edwards A, Ensom MH. Pharmacokinetic effects of bariatric surgery. Ann Pharmacother. 2012 Jan;46(1):130-6. Epub 2011 Dec 20.

Decker GA, Swain JM, Crowell MD, et al. Gastrointestinal and nutritional complications after bariatric surgery. Am J Gastroenterol. 2007 Nov;102(11):2571-80; quiz 2581. Epub 2007 Jul 19.

Shikora SA, Kim JJ, Tarnoff ME. Nutrition and gastrointestinal complications of bariatric surgery. Nutr Clin Pract. 2007 Feb;22(1):29-40. Review.

Ponsky TA, Brody F, Pucci E. Alterations in gastrointestinal physiology after Roux-en-Y gastric bypass. J Am Coll Surg. 2005 Jul;201(1):125-31.

10 facts on obesity. World Health Organization.www.who.int/features/factfiles/obesity/en/. Published 2010. Accessed March 17, 2012.

Facts About Obesity in the United States. Centers for Disease Control and Prevention. http://www.cdc.gov/obesity/. Accessed March 17, 2012.