Orthopedics

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Pharmacology Update 

Medication Use in Bariatric Surgery Patients: What Orthopedists Need to Know

April D. Miller, PharmD; Kelly M. Smith, PharmD

Abstract

By understanding bariatric surgery procedures performed and the need for additional medication management, optimal outcomes can be achieved in these patients.

Obesity, defined as a body mass index (BMI) >30, affects approximately 50 million Americans.1 In recent years, there has been an increase in the number of bariatric surgeries performed annually. According to the American Society for Bariatric Surgery, in the early 1990s, approximately 16,000 procedures were performed annually and in 2003 approximately 103,000 procedures were performed. The increase means that orthopedists are more likely to encounter these patients and manage issues related to medication use in this population.

The two major categories of bariatric surgery are restrictive procedures and combination restrictive/malabsorptive procedures.2-4 Restrictive procedures include vertical banded gastroplasty and adjustable gastric banding. These restrictive procedures partition a small pouch at the top of the stomach, restricting the quantity of food patients can consume at a time. A small 1-cm hole is created at the bottom to retain food in the pouch and maintain a sensation of fullness for a prolonged period.2-4

Combination restrictive/malabsorptive procedures ordinarily performed include biliopancreatic diversion and the Roux-En-Y gastric bypass. The Roux-En-Y procedure is the most commonly performed bariatric surgery procedure in the United States.2-4 The restrictive portion of these procedures creates a pouch at the top of the stomach to restrict intake and create a sensation of fullness. The malabsorptive portion reconnects the small intestine to the stomach, bypassing a portion. With a less functional intestine, patients absorb fewer calories ingested. Biliopancreatic diversion bypasses more of the small intestine and places patients at increased risk for malnutrition. It is generally reserved for the extremely obese patient with a BMI of >50.

Drug characteristics and the surface area for absorption influence the absorption and bioavailability of drugs. When drugs are given in tablet or capsule form, they must dissolve before absorption occurs.5 Drug solubility affects absorption and is influenced by the pH. The pouch formed at the top of the stomach in bariatric surgery procedures produces much less hydrochloric acid than the stomach as a whole. Drugs dependent on acidic pH for absorption will have reduced absorption, and therefore, reduced efficacy in patients who have had bariatric surgery.

In combination restrictive/malabsorptive procedures, major portions of the small intestine are bypassed to reduce caloric absorption. This also affects the available surface area for drug absorption and can theoretically affect all drugs administered in these patients. Because these procedures bypass the duodenum, medications absorbed in the duodenum are likely to exhibit decreased bioavailability. Extended or sustained-release dosage forms with prolonged absorptive phases are likely to exhibit reduced bioavailability.

Physiologic changes in the gastrointestinal tract place bariatric surgery patients at risk for malnutrition and necessitate nutrient replacement. Deficiencies are less common with restrictive procedures, but have been reported.6 After combination restrictive/malabsorptive procedures, patients are especially prone to deficiencies of the fat soluble vitamins (A, D, E, and K) and calcium.6,7 Deficiencies in iron, vitamin B12, and folate make anemia a common postoperative problem. This is especially important to consider in orthopedic patients preoperatively, where further work-up of deficiencies may be necessary in patients with low hemoglobin and hematocrit. In addition, it is recommended that gastric bypass patients receive a daily multivitamin indefinitely.6,7

The specifics of nutrient deficiencies in the bariatric surgery population are discussed elsewhere and this article focuses on the importance of formulation selection in these patients.6,7 As previously discussed, bariatric surgery patients produce very little gastric acid. Iron and some calcium salts are dependent on acid for absorption, and these problems can be overcome by formulation changes and manipulating gastric pH.6-8 A study of calcium bioavailability…

By understanding bariatric surgery procedures performed and the need for additional medication management, optimal outcomes can be achieved in these patients.

Obesity, defined as a body mass index (BMI) >30, affects approximately 50 million Americans.1 In recent years, there has been an increase in the number of bariatric surgeries performed annually. According to the American Society for Bariatric Surgery, in the early 1990s, approximately 16,000 procedures were performed annually and in 2003 approximately 103,000 procedures were performed. The increase means that orthopedists are more likely to encounter these patients and manage issues related to medication use in this population.

Bariatric Surgery Procedures

The two major categories of bariatric surgery are restrictive procedures and combination restrictive/malabsorptive procedures.2-4 Restrictive procedures include vertical banded gastroplasty and adjustable gastric banding. These restrictive procedures partition a small pouch at the top of the stomach, restricting the quantity of food patients can consume at a time. A small 1-cm hole is created at the bottom to retain food in the pouch and maintain a sensation of fullness for a prolonged period.2-4

Combination restrictive/malabsorptive procedures ordinarily performed include biliopancreatic diversion and the Roux-En-Y gastric bypass. The Roux-En-Y procedure is the most commonly performed bariatric surgery procedure in the United States.2-4 The restrictive portion of these procedures creates a pouch at the top of the stomach to restrict intake and create a sensation of fullness. The malabsorptive portion reconnects the small intestine to the stomach, bypassing a portion. With a less functional intestine, patients absorb fewer calories ingested. Biliopancreatic diversion bypasses more of the small intestine and places patients at increased risk for malnutrition. It is generally reserved for the extremely obese patient with a BMI of >50.

Drug Characteristics & Physiologic Issues Related to Absorption in Bariatric Surgery Patients

Drug characteristics and the surface area for absorption influence the absorption and bioavailability of drugs. When drugs are given in tablet or capsule form, they must dissolve before absorption occurs.5 Drug solubility affects absorption and is influenced by the pH. The pouch formed at the top of the stomach in bariatric surgery procedures produces much less hydrochloric acid than the stomach as a whole. Drugs dependent on acidic pH for absorption will have reduced absorption, and therefore, reduced efficacy in patients who have had bariatric surgery.

In combination restrictive/malabsorptive procedures, major portions of the small intestine are bypassed to reduce caloric absorption. This also affects the available surface area for drug absorption and can theoretically affect all drugs administered in these patients. Because these procedures bypass the duodenum, medications absorbed in the duodenum are likely to exhibit decreased bioavailability. Extended or sustained-release dosage forms with prolonged absorptive phases are likely to exhibit reduced bioavailability.

Considerations In Nutrient Replacement

Physiologic changes in the gastrointestinal tract place bariatric surgery patients at risk for malnutrition and necessitate nutrient replacement. Deficiencies are less common with restrictive procedures, but have been reported.6 After combination restrictive/malabsorptive procedures, patients are especially prone to deficiencies of the fat soluble vitamins (A, D, E, and K) and calcium.6,7 Deficiencies in iron, vitamin B12, and folate make anemia a common postoperative problem. This is especially important to consider in orthopedic patients preoperatively, where further work-up of deficiencies may be necessary in patients with low hemoglobin and hematocrit. In addition, it is recommended that gastric bypass patients receive a daily multivitamin indefinitely.6,7

The specifics of nutrient deficiencies in the bariatric surgery population are discussed elsewhere and this article focuses on the importance of formulation selection in these patients.6,7 As previously discussed, bariatric surgery patients produce very little gastric acid. Iron and some calcium salts are dependent on acid for absorption, and these problems can be overcome by formulation changes and manipulating gastric pH.6-8 A study of calcium bioavailability in achlorhydric patients found calcium carbonate bioavailability to be 4% and calcium citrate to be 45%.9 Although more expensive, a specific recommendation for calcium citrate supplementation is appropriate in gastric bypass patients.

The Roux-En-Y procedure bypasses the duodenum, which is the principal site for iron absorption, leaving patients at risk for deficiency. The acid environment of the normal stomach converts iron from the normal dietary form (ferric) to the absorbable ferrous form. To facilitate the absorption of iron products in gastric bypass patients, they can be combined with ascorbic acid (Vitamin C) to acidify the stomach environment.8,10

Vitamin B12 or cobalamin depends on the presence of intrinsic factor from the stomach for its absorption and gastric bypass patients are subject to deficiencies.11 While monthly injections are effective, supplementation with 1000 mcg by mouth daily is also appropriate.12

General Medication Considerations

Some general guidelines on medication considerations in the bariatric surgery population can be postulated. While little documented evidence exists, bariatric surgery centers recommend avoiding nonsteroidal anti-inflammatory drug (NSAID) use due to an increased risk of ulceration and bleeding from reduced pouch size.13-15 Given the similarities to NSAIDs salicylates, they also should be avoided in this population.

Pharmacologic alternatives for chronic pain control in these patients are limited to acetaminophen, opioids, and tramadol. Tramadol is a centrally acting analgesic affecting opioid receptors with a low abuse potential. Oral bisphosphonates used in the treatment of osteoporosis also have an increased potential for gastrointestinal ulceration.16 Other options to increase bone density in these patients include calcitonin salmon nasal spray, teriparatide (synthetic parathyroid hormone), and raloxifene in women.

While no specific data exists on gastric surgery patients, the nausea, vomiting, and epigastric discomfort associated with glucosamine could occur more frequently in this population. Additional patient monitoring for these side effects is appropriate. Since chondroitin does not carry the same risk of these side effects, gastric bypass patients are likely to tolerate therapy well. Methotrexate is not specifically contraindicated, however reduced oral absorption could lead to decreased efficacy. Warfarin, another common agent in the orthopedic population, is not specifically contraindicated, however, decreased absorption may mean that patients require larger doses to achieve therapeutic International Normalized Ratios (INRs). These dose adjustments should only be made after normal doses fail to bring a patient’s INR into the desired range.

Patients who have undergone bypass procedures are more susceptible to difficulties with drug absorption due to reduced functional intestine length. Extended, sustained, and delayed release formulations are passed through the gastrointestinal tract before complete absorption can occur. This is also a potential problem with enteric-coated forms of drugs. Immediate-release formulations should be substituted in these patients. It is important to ensure that the dose of extended-release formulations is converted to an equivalent immediate-release formulation.

All agents have the potential for decreased absorption in gastric bypass patients, but changes in dose or product formulation are not always necessary. Since reduced absorption means less drug efficacy, increased patient monitoring for therapeutic effects of prescribed agents is appropriate. If patients are not experiencing the desired effect from prescribed agents, some changes could improve efficacy. Using liquid product formulations could enhance absorption by eliminating the need for drug dissolution. Other routes, including rectally, vaginally, and transdermally could also be considered, if available. By working with patients, these small changes can improve patient outcomes. The table outlines common oral medications for orthopedic patients and relevant medication concerns.

Table

Conclusion

As the number of bariatric surgeries performed annually continues to increase, orthopedists are more likely to encounter medication concerns in these patients. By understanding the procedures performed and the need for additional medication management, optimal outcomes can be achieved in these patients.

The Bottom Line

  • Patients post-bariatric surgery require special consideration when prescribing oral medications
  • Calcium should be supplemented in this population with the citrate salt because of improved bioavailability.
  • NSAIDs, salicylates, and bisphosphonates should be avoided due to increased risk of gastrointestinal ulceration.
  • Drugs with prolonged absorption times (extended-release, sustained release, and enteric coated) and drugs absorbed in the duodenum demonstrate reduced bioavailability in bariatric surgery patients (see table).
  • Liquid product formulations and other routes of administration can improve medication outcomes in bariatric surgery patients.

References

  1. Buchwald H, Avidor Y, Braunwald E et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004; 292:1724-1737.
  2. Fussy SA. The skinny on gastric bypass. US Pharm. Available at: http://www.uspharmacist.com/index.asp?show=article&page=8_1438.htm. Accessed October 11, 2005.
  3. Hydock CM. A brief overview of bariatric surgical procedures currently being used to treat the obese patient. Crit Care Nurs Q. 2005; 28:217-226.
  4. O’Brien PE, Brown WA, Dixon JB. Obesity, weight loss and bariatric surgery. Med J Aust. 2005; 183:310-314.
  5. Benet LZ, Kroetz DL, Sheiner LB. Pharmacokinetics: the dynamics of drug absorption, distribution and elimination. In: Gilman GG, Limbird LE, Molinoff PB, Raymond RW, eds. Goodman and Gilman’s: the Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1995:3-27.
  6. Brolin RE. Metabolic deficiencies and supplements following bariatric operations. In: Martin LF, ed. Obesity surgery. 1st ed. New York, NY: The McGraw-Hill Co; 2004:275-299.
  7. Ponsky TA, Brody F, Pucci E. Alterations in gastrointestinal physiology after Roux-En-Y gastric bypass. J Am Coll Surg. 2005; 201:125-131.
  8. Rhode BM, Shustik C, Christou NV, MacLean LD. Iron absorption and therapy after gastric bypass. Obes Surg. 1999; 9:17-21.
  9. Recker RR. Calcium absorption and achlorhydria. N Eng J Med. 1985; 313:70-73.
  10. Harju E. Clinical pharmacokinetics of iron preparations. Clin Pharmacokinet. 1989; 17:69-89.
  11. Behrns KE, Smith CD, Sarr MG. Prospective evaluation of gastric acid secretion and cobalamin absorption following gastric bypass for clinically severe obesity. Dig Dis Sci. 1994; 39:315-320.
  12. Smith CD, Herkes SB, Behrns KE. Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity. Ann Surg. 1993; 218:91-96.
  13. Bielefeldt K. Not just an ulcer. Case-based learning in gastroenterology and hepatology: esophageal disorders. Available at: http://www.vh.org/adult/provider/internalmedicine/GICases/Esophageal/Ulcer/Ulcer.html Accessed October 11, 2005.
  14. Sapala JA, Wood MH, Sapala MA, Flake TM. Marginal ulcer after gastric bypass: a prospective 3-year study of 173 patients. Obes Surg. 1998; 8:505-516.
  15. Northwest Center for Weight Management. Frequently asked questions. Available at: https://www.fhshealth.org/bariatric/faq.asp#medsAvoid. Accessed October 11, 2005.
  16. Fosamax (package insert). Whitehouse Station, NJ: Merck & Co, Inc. 2005.
  17. Franklin MR, Franz DN. Drug absorption, action, and disposition. In: Gennaro AR, ed. Remington: the Science and Practice of Pharmacy. 20th ed. Baltimore, Md: Lippincott, Williams, and Wilkins; 2000:1098-1126.
  18. Pinchiera JC, Prince RA, Mason EE. Effect of bariatric surgery on erythromycin absorption. Am J Hosp Pharm. 1981; 38:232.

Authors

Drs Miller and Smith are from the University of Kentucky College of Pharmacy, Chandler Medical Center, Lexington, Ky.

Reprint requests: Kelly M. Smith, PharmD, University of Kentucky College of Pharmacy, 800 Rose St, C-117, Lexington, KY 40536-0293.

10.3928/01477447-20060201-09

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