Transcript Slide 1

A Review of Gastric Bypass:
Implications for Pharmacotherapy and
Disease State Management
David G. Fuentes, PharmD BCPP CGP
Assistant Professor
Pacific University of Oregon
School of Pharmacy
Educational Outline
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Describing Gastric Bypass (GB)
Risk factors associated with a need for GB
Common system co-morbidities in patients undergoing GB
Clinical evaluation and monitoring parameters before and after
GB
Post-GB changes in metabolism and absorption
Review of the literature regarding GB
Implications on drug therapy
Case scenarios and concept application
Gastric Bypass (GB)
• Terminology
– Weight loss surgery (WLS) 1, 2
– Open surgery 1
– Laparoscopy adjustable gastric banding (LAGB) 1, 5-7
– Bariatric surgery 3, 4
– Gastric banding 3
– Roux-en-Y gastric bypass (RYGB) 4, 6, 8
– Hand-assisted laparoscopic Roux-en-Y gastric
bypass (HALGB) 9
Major General Approaches to GB
• Adult patients: emerging increase in laparscopic
adjustable banding approach 5
– Review of approx. 31,300 surgeries (2004 – 2007)
• Adjustable banding: 7%  23%
• Gastric bypass (GB): 53  66%
• Pediatric patients: greater use of RYGB and
LAGB (non-FDA approved) 6, 10
• Medication and adjustable gastric banding
(AGB) 7
– Adding orlistat prescription dose
The Impact of GB in the US
• Increasing trends 2
– Example: Wisconsin inpatient hospital
• Approx. 50 procedures (1990 – 1992)
• Approx. 1880 procedures (2000 – 2002)
• Health policy and financial implications 1, 3, 11
– Funding available based on conditions
• Accreditation in WLS, use of multi-disciplinary care
• Emerging Benefits 1, 4, 12
– Reduction in weight correlating with improvements
in chronic conditions
Common Co-morbid Systems in GB Patients
• Systems: Cardiac, endocrine, gastrointestinal,
neuro-psychiatric, fetal-reproductive, vascular
• Degrees of obesity 9, 11-13
– Morbidly obese: Body mass index (BMI) > 40 kg/m2
– Super obese: BMI > 50 kg/m2
Evaluation Prior to GB
• Approaching GB pre-assessment as a patientspecific process 7, 8, 14-19
– Holistic patient evaluation
• Socioeconomic, access to care, age, chronic diseases,
ongoing risk factors, baseline physical measures and
objective data, ongoing stressors and mental health
• Importance of gauging general health, cognitive
and physical abilities, specific expectations and
co-morbidities 8, 11, 13, 15, 17
Pharmacological Considerations after GB
• Inter-patient variability is common
– Lab values and deficits can clinically stabilize and
improve within 2 yrs 20, 21
– Higher baseline BMI, diabetes and on multi-drug
regimens experienced excessive weight loss (EWL)
21, 22
– Electrolytes may be severely affected and
monitoring may be necessary 21, 23
• May complicate medication options and increase
monitoring burdens
Changes in Absorption after GB
• Digestion and absorption of fats was reduced in patients
depending on the procedure 16, 24
• Reported shift in the GI micro-flora affecting digestion and
absorption 25
• General absorption is diminished greatly status-post (s/p)
bariatric surgery 26, 27
• Case reports involve jejuno-ileal bypass, gastric
bypass/gastroplasty and bilio-pancreatic diversion 26
Changes in Metabolism after GB
• Altered medication absorption and metabolism
are reported as drug-specific 26
• Altered properties affecting medications’
physical properties, pharmacokinetics and
dynamics 26, 28
– Medication dissolution
– Medications absorption
– Handling of lipophilic agents
– Enterohepatic recirculation
Impact of GB on Pharmacotherapy
and Disease State Management
• Implicated in improvement of chronic conditions
– Weight reduction, cost savings, improved chronic health conditions, and
reduced all-cause mortality 1, 2, 8, 12, 29-36
– Gastro-esophageal reflux disease (GERD) 4, 37-38
– Generally improved quality of life (QOL) 38-39
– Prevention of complications associated with pregnancy 40
– Does not consistently affect conception or fetal development in a
negative manner 41-43
• Negative conditions s/p GB
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Chronic anemia secondary to reduced intestinal absorption 44
Delayed hyperinsulinemic - hypoglycemic response after RYGB 45
Reduced GI motility after gastric banding 46
Gallstone and renal stone formation 1, 5, 6, 14, 45
Specific Implications for Drug-Therapy
• Medications requiring narrow therapeutic
window maintenance for safety and efficacy
• Example in an RYGB patient 47
– Patient using phenytoin and previously controlled
x30 years
Specific Implications for Drug-Therapy
• Review of medication absorption s/p GB
procedure finds diminishing levels and possibly
related reduced efficacy 26
– Cyclosporine
– Levothyroxine
– Phenytoin
– Rifampin
– Antibiotics
Specific Implications for Drug-Therapy
• Treatment of malignancy was suspected to
adversely affect temozolomide levels 48
• A time for investigation
– Patients exhibiting treatment failure were tested for
medication levels
– Concentrations were not different between GB and
non-GB patients
• Authors of this report and other investigations
concluded that drug kinetics must be evaluated
on “drug-by-drug basis” 48-50
Specific Implications for Drug-Therapy
• A case report highlights possible warfarin
resistance thought to be linked to recent total
gastrectomy with a Roux-en-Y esophagojejunostomy procedure 51
– Previously stabilized 71-year old woman with
chronic atrial fibrillation on approx. 5 mg/day
– Patient underwent surgery and was bridged to
outpatient afterwards to INR 2.0-3.0
– Months later she required up to 20 mg/day of
warfarin for INR 2.0 – 3.0
Specific Implications for Drug-Therapy
• Starting drug therapy sooner to preserve bone
health and integrity? 23, 27
– Younger GB patients may be requiring more
calcium supplements and vitamin D therapy
– Hormonal therapy may be indicated sooner for
females at risk
Specific Implications for Drug-Therapy
• Control of Parkinson’s disease reported 52
– Patients were controlled previously with chronic
levodopa therapy
– Evidence reviewed showed that having frequent “on
and off” fluctuations were correlated to the
pharmacokinetics related to the GI system and
absorption (reduced gastric emptying)
– Patients s/p GB did much better on intravenous
trials of levodopa ethyl-ester injections which
bypass the GI
Specific Implications for Drug-Therapy
• Additional supplementation and s/p GB
medications 27, 42, 53-54
– Major elements considered to be missing include: calcium,
vitamins A, D, E and K, multiple vitamins, iron, folate, and
cyanocobalamin 53
– Ursodeoxycholic acid after GB to prevent gallstones 14, 45
– Babies born to mothers s/p GB may require monitoring and
supplementation of B12
– Pregnant women should adhere to folic acid
supplementation 16-17, 55
– Vitamin excess should be avoided and patient-specific
needs should be targeted 56-57
Case 1
• JK is a 38 year old patient using fluoxetine,
olanzapine, lithium, “as needed” zolpidem,
nightly temazepam, lisinopril, metoprolol
tartrate, enteric coated aspirin, “as needed”
ibuprofen
• He drinks alcohol when his depression is
worsened. He thinks his medications are losing
their efficacy due to his GB (surgery done
RYGB 1.5 years ago)
Case 2
• BC is a 35 year old female wanting to seek help
for her depression. She has “tried it all” and is
open to using anything.
• She is also complaining about her chronic pain
becoming worse. She has been using
oxycodone 80 mg PO TID, “as needed”
oxycodone/acetaminophen, gabapentin, and
twice-daily cyclobenzaprine.
Emerging and Difficult Issues
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Procedure failure 8
Pediatrics: childhood obesity 6
Alternative surgical procedures 3, 6
Good weight loss vs. EWL 21
Lack of data specific to drug dissolution disposition in
BMI > 40 kg/m2 and s/p GB 28, 49
• The impact of vitamin D depletion on HTN control 43
• Greater sensitivity to drug-induced ulceration 42
• Immediate and longitudinal follow-up 4, 6, 9
Desired Data and Information Sets
• Specific information on dosing in special
populations
• Targets of knowledge and clinical research
– Starting doses and variation in release forms/salts
– Active metabolites and elimination
– Chronic maintenance doses
• Should the drug dose change as the disease changes?
– Possible changes in adherence patterns
– Educating pharmacists on signs of medication
treatment failure
Conclusion
• Much more information and practice pearls are
necessary as they pertain to medication dosing,
use and efficacy after GB procedures
• GB procedures are becoming extremely
common in various populations
• Long-term nutritional deficits will need to be
investigated and effectively treated in this
population
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