US Pharm. 2012;37(9):HS-12-HS-16.
Obesity continues to be an epidemic affecting a staggering proportion
of the U.S. population. The latest CDC data reveal that, in 2009–2010,
almost 41 million women and more than 37 million men aged 20 years and
older were obese—more than 35% of the population.1
Individuals who are overweight or obese have an increased risk of
all-cause mortality and a much greater risk of various health
conditions, including coronary heart disease, hypertension, type 2
diabetes, dyslipidemia, stroke, gallbladder disease, osteoarthritis,
sleep apnea and respiratory problems, and endometrial, breast, prostate,
and colon cancers, among others.2,3 Additionally, women may
be significantly affected by other obesity-associated diseases, such as
gynecologic abnormalities (i.e., problems with menses and fertility), as
well as disorders such as stress incontinence. Among obesity-related
conditions, heart disease, cancer, stroke, and diabetes are among the
top 10 causes of death in women.4 Clearly, treating obesity is essential to women’s health.
Bariatric surgery is an obesity treatment that has been performed
over the years with a variety of approaches, and the number of
procedures performed has increased as the struggle with this epidemic
continues. The American Society for Metabolic and Bariatric Surgery
estimates that the number of bariatric procedures in the U.S. increased
from 13,365 in 1998 to 150,000 in 2005, and to around 200,000 in 2007.5
Given the large percentage of the population affected by obesity, these
numbers will probably continue to rise. As the number of patients who
have had bariatric surgery increases, the pharmacist can play a crucial
role in determining needed medication adjustments to optimize medication
therapy in these patients.
BARIATRIC SURGERY: QUALIFICATIONS AND TYPES OF PROCEDURES
In order to determine which patients are possible candidates for
bariatric surgery, further classification of obesity is needed. The
National Institutes of Health’s clinical guidelines on identifying and
treating obesity define obesity as a BMI ≥30 kg/m2.2
Severity of obesity is further categorized into classes I, II, and III,
with some sources going beyond class III to subcategorize obesity
severity. Class I is defined as a BMI of 30.0 to 34.9, class II is a BMI
of 35.0 to 39.9, and class III (extreme obesity) is a BMI of ≥40 kg/m2.
Further breakdown of obesity prevalence data from CDC 2007–2008
statistics reveals specifics as to what proportion of the U.S.
population falls into classes II and III: In 2007–2008, 14.3% of adults
aged 20 years or older had a BMI of ≥35 kg/m2, and 5.7% had a BMI ≥40 kg/m2.6
The aforementioned clinical guidelines on obesity, as well as other
publications on bariatric surgery for severe obesity, provide guidance
as to which patients may be candidates for this treatment.2,7 Bariatric surgery may be an option in patients with a BMI ≥40 kg/m2 and in those with a BMI ≥35 kg/m2
who have comorbid conditions, so both class II and class III patients
are potential candidates. Patients must also have tried and failed
traditional, less invasive means of weight loss; have acceptable
operative risks; and be able to participate in treatment and follow-up,
as well as understand the surgical procedure and what practices they
must follow in the long term.
Types of Bariatric Procedures
To fully understand the potential impact of bariatric surgery on drug
therapy and other considerations, the various types of procedures must
be examined. Bariatric procedures generally either use gastric
restriction to stimulate weight loss by limiting food intake and causing
an early feeling of satiation or are a hybrid of gastric restriction
and induction of some type of malabsorption in the gastrointestinal (GI)
tract.5 Procedures that involve gastric restriction alone
include laparoscopic adjustable gastric banding, vertical banded
gastroplasty, and sleeve gastrectomy. Procedures that combine gastric
restriction and malabsorption include Roux-en-Y gastric bypass and
biliopancreatic diversion with duodenal switch. One of the early
procedures designed for weight loss, jejunoileal bypass, was a purely
malabsorptive procedure in which the stomach was kept intact, but most
of the intestines were bypassed.8 Owing to the significant
complications that patients experienced with this type of procedure,
however, this type of surgery is no longer recommended.
Gastric Restriction: Laparoscopic adjustable gastric banding
involves wrapping an inflatable band around a small portion of the
upper stomach, creating a small area where food can enter and a narrow
opening to the rest of the stomach.9 The band is connected
via tubing to a subcutaneous reservoir to allow saline to be injected to
control the degree of gastric restriction. In this procedure, the
stomach is not removed and the intestines are not bypassed. Sleeve gastrectomy is another restrictive procedure in which most of the stomach is removed, leaving a sleeve- or cylinder-shaped stomach. Vertical banded gastroplasty
involves stomach stapling to partition off a small part of the stomach
for the esophagus to empty into, and also uses a band to create a narrow
opening to the rest of the stomach.10
Combined Gastric Restriction and Malabsorption: In Roux-en-Y gastric bypass, a small pouch is created from the upper part of the stomach and separated from the remainder of the stomach.9
The small intestine is then separated into two limbs at the middle part
of the jejunum (bypassing rest of stomach and duodenum), and the lower
portion (alimentary/Roux limb) is connected via anastomosis to the newly
created gastric pouch. The lower part of the stomach and the upper
small intestine (biliopancreatic limb) are then reconnected via
anastomosis further down the jejunum, creating a “Y” configuration.
There are variations in how long these limbs are made and how far down
the biliopancreatic limb is reconnected, which can affect absorption
significantly, since a shorter common channel below the reconnection can
limit contact with biliary and pancreatic secretions.5,9
Biliopancreatic diversion with duodenal switch involves less
gastric restriction than Roux-en-Y gastric bypass, but a large portion
of the stomach is removed using the sleeve gastrectomy procedure
described above. For the malabsorptive component of biliopancreatic
diversion, the portion of intestine that is bypassed is much longer than
with Roux-en-Y.11 The duodenum is cut about 2 cm from the
stomach, and the lower part of the small intestine (latter part of
ileum, about 50-100 cm from colon) is reconnected where the duodenum was
cut. The bypassed limb that was severed from the stomach is reconnected
to the lower part of the small intestine to create a small common
channel to the colon in a fashion similar to the Roux-en-Y procedure.
Variations: Of the available bariatric surgery
procedures, Roux-en-Y gastric bypass and laparoscopic adjustable gastric
banding are the types most commonly performed.12 These
procedures therefore are the ones pharmacists are most likely to
encounter in patients, but they are not the only available options, and
they are also subject to a number of surgical variations; additionally,
in some patients, multiple or combination procedures may have been
performed. It is important to keep the specific patient and procedure(s)
in mind when considering potential drug therapy implications.
POTENTIAL DRUG CONSIDERATIONS
There are multiple factors for a pharmacist to consider in the
postoperative medication management of a bariatric surgery patient.
These include how the procedure relates to the drug’s mode of
absorption; how the drug is released; other properties of the drug and
how they will impact a patient who has had surgical resection or
GI-tract alteration; how the drug’s properties relate to a patient
struggling with obesity; how drug distribution is affected overall by
obesity; and changes in patient medication needs as weight loss occurs.
There are multiple steps in the process of medication absorption, as
well as a number of complex factors to consider. When a medication is
given orally versus IV, the processes that a medication goes through to
be absorbed and the medication’s bioavailability must be taken into
account. When medications are given in a solid dosage form (e.g., tablet
or capsule), disintegration, dissolution, and solubility are key.13,14
The stomach is the primary site for drug disintegration; the mixing
involves a combination of saliva, gastric acid, and movement to break
down the dosage form and allow for smaller particle sizes that are more
easily absorbed in the GI tract. This action could be substantially
reduced in the case of any bariatric procedure involving gastric
restriction because of the limited potential for this to occur in a
smaller area of stomach.
Dissolution of solid dosage forms also may be impaired because of
restriction, and solubility can be altered, particularly in cases in
which the pH of the stomach environment has changed.13,14 In
procedures such as Roux-en-Y gastric bypass, vertical-banded
gastroplasty, and those involving sleeve gastrectomy (in which part of
the stomach is partitioned off or removed), drugs no longer pass through
the majority of the stomach, where most of the acid-producing cells are
housed. This creates a more alkaline environment that can affect the
disintegration, dissolution, and solubility of some medications.
Oral-solution formulations would be expected to be less impacted by
changes in these processes since the drug particles are already
dissolved. Therefore, dosage-form options should be taken into
consideration for bariatric surgery patients postoperatively.13,14
The discussed changes are important considerations in cases of
restrictive procedures, but patients who have had their intestines
altered require further examination of the potential impact of their
bariatric procedure owing to the great amount of drug absorption that
occurs in the small intestine.
The small intestine is a complex organ with a vast surface area
because of villi and other features; a multitude of cell types; and
neural and vascular innervation that allow for multiple mechanisms
affecting absorption.15 Some of the factors that should be
considered include passive diffusion of medications across the
epithelium of the GI tract; the effect of transport functions (efflux
and uptake) on medication absorption; presystemic metabolism, in which
prodrugs require transformation into their active form; medications that
rely on mixing with bile acids and enterohepatic circulations for
maximum absorption; and the overall effect on site, timing, and extent
of absorption, since GI length and mucosal exposure are being
Recommending Medication Adjustments
A key area where pharmacists can make recommendations for medication
adjustments is dosage form. The pharmacist should consider recommending
formulations that do not rely heavily on the stomach for disintegration
and dissolution (e.g., liquid forms, orally disintegrating tablets,
nonoral forms); he or she should also contemplate switching the patient
to immediate-release formulations, since extended-release and
sustained-release formulations generally have slow dissolution and an
extended absorption period that could cause the medication not to be
absorbed in cases when part of the intestine is bypassed and the length
of the intestine is reduced.13,14,16,17
Other drug properties that should be considered in post–bariatric
surgery patients include the propensity of a medication to irritate the
GI tract and the tendency of certain drugs to promote weight gain and
increase appetite.13,14,16,17 Data are limited regarding
pharmacokinetics in patients who are obese and those who have undergone
bariatric surgery; however, attention should be paid to how drug
distribution and absorption are affected by obesity, given how
hydrophilic or lipophilic the drug is, what types of tissues it
subsequently distributes into (lean body mass or fatty tissue), and the
effect of obesity on medication clearance.18
All this should be kept in mind while recognizing that a key strategy
involves dosing and monitoring based on therapeutic outcome.18
It is important to remember that medication needs can change in the
post–bariatric surgery patient as weight loss occurs and chronic
conditions improve.18 These conditions include—but are not
limited to—many of the obesity-related conditions previously mentioned,
such as heart disease and related disorders (diabetes, hypertension,
dyslipidemia, etc.), respiratory problems, and osteoarthritis.
SELECTED ISSUES AFFECTING WOMEN’S HEALTH
The discussed considerations are applicable to both women and men who
have undergone bariatric surgery, but some key areas are worth
examining in terms of women’s health given the obesity-related
conditions that women face and the medications used to treat these and
other conditions in women.
In women, fertility problems can be related to obesity.2,3
Although data on the effect of bariatric surgery on fertility is
limited, it is well established that weight loss can improve fertility,
and increased fertility after surgery is suggested in the bariatric
population as well.19-21 It is estimated that almost half of
bariatric procedures are performed in women aged 18 to 45 years, so it
is crucial to consider the impact on fertility in this patient
Since oral contraceptives (OCs) may be subject to extensive
first-pass metabolism and enterohepatic circulation, absorption and
efficacy may be reduced in bariatric surgery patients, especially
considering the low hormonal dosages used in OCs.13,20,21
Given the potential for increased fertility and decreased OC efficacy
and the paucity of clinical data, the pharmacist may consider
recommending other forms of contraception to patients, including barrier
methods and non-OCs such as intrauterine devices, vaginal rings, and
injectable contraceptives, keeping in mind the potential effects of
obesity on volume of distribution and drug concentrations in the plasma.20,21
Another issue not specifically related to contraception but important
in post–bariatric surgery in women of reproductive age is that,
according to guidelines, iron supplementation may be needed to prevent
nutritional anemias, especially in menstruating women.5 The
guidelines also contain information regarding giving vitamin C with iron
to increase absorption given the need for an acidic environment.
A major women’s health issue in general, osteoporosis is especially
important to consider in bariatric surgery patients, who may be at
greater risk owing to decreased intake of nutrients and the possibility
of reduced absorption of calcium and fat-soluble vitamins such as
vitamin D.16,21,22 Multivitamin supplementation including calcium and vitamin D is generally recommended following bariatric surgery.5
An important point to remember regarding patients who have undergone a
procedure involving restriction in which the acid-producing cells have
been partitioned off is that the stomach will generally have a higher
Another important consideration is the potential for absorption issues with calcium carbonate in these patients.16,22,23
The National Osteoporosis Foundation encourages patients to take
calcium supplements with food to increase stomach acid production for
optimal absorption, while pointing out that calcium citrate can be
absorbed at any time.24 Data suggest that calcium carbonate absorption is impaired when stomach acidity is decreased.16,25
Considering this information, calcium citrate is a reasonable
recommendation for pharmacists to make to bariatric patients. Absorption
and GI toxicity are issues with bisphosphonate treatment for
osteoporosis, so the use of IV formulations should be considered.5,16,21,22 Depending upon the scenario, alternative osteoporosis treatments may be kept in mind.
Extremely obese patients are more likely to have psychiatric disorders, most commonly mood disorders.5
These patients also may experience increased symptoms of depression and
other psychiatric disorders. Additionally, depression is more common in
women than in men.26 Given the large proportion of women
affected by obesity and undergoing bariatric surgery, psychiatric
disorders in this population and the medications used to treat them are
an important consideration for pharmacists. Examination of the
pharmacokinetics of various medication classes in the bariatric surgery
population has brought to light some issues with psychiatric medications
regarding site of absorption based on data for the individual agent,
bioavailability changes when the medication is administered with food,
and drug-distribution problems in obese patients.13,14,16,18
Another important consideration in the treatment of psychiatric
disorders in this population is the propensity of these medications to
cause weight gain and/or increase appetite. Since many antidepressants,
antipsychotics, and other agents used for psychiatric disorders have
this potential, medication therapy in the bariatric surgery patient
should be closely examined by the pharmacist in this regard, and any
needed changes made to optimize a patient’s therapy.16
There are a multitude of factors to consider in optimizing medication
use in patients who have undergone bariatric surgery. Pharmacists can
play a key role in identifying ways to prevent and correct problems by
taking into account each patient’s specific needs and utilizing their
knowledge of drugs. This is especially crucial in the absence of
sufficient clinical data examining potential medication issues in this
patient population. Obesity affects women in numerous ways. Although
many of the challenges seen and recommendations that can be made hold
true for both men and women, particular attention is needed in the areas
discussed, as well as other areas involving needs that are unique to
women or where women may be disproportionately affected.
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20. Merhi ZO. Challenging oral contraception after weight loss by bariatric surgery. Gynecol Obstet Invest. 2007;64:100-102.
21. Chan L-N. Drug therapy related-issues in patients who received bariatric surgery (part 2). Pract Gastroenterol. 2010;34:24-32.
22. Williams SE. Metabolic bone disease in the bariatric surgery patient. J Obes. 2011;2011:634614.
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25. Shangraw RF. Factors to consider in the selection of a calcium supplement. Public Health Rep. 1989;104(suppl):46-50.
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