Gastroesophageal Reflux Disease

Elizabeth Y. Tan, RPh MS Pharm

Faculty, Department of Pharmacy
University of San Carlos Cebu City, Philippines

DEFINITION
Gastroesophageal reflux disease (GERD) is a common
medical disorder.
It refers to symptoms or mucosal damage that results
from abnormal reflux of the stomach contents into the
esophagus.
When the esophagus is repeatedly exposed to refluxed
material for prolonged periods of time, inflammation of
the esophagus (reflux esophagitis) occurs, and in some
cases, it can progress to erosion of the squamous
epithelium of the esophagus (erosive esophagitis).

PATHOPHYSIOLOGY
abnormal reflux of gastric contents
from the stomach into the esophagus.
defective lower esophageal sphincter
(LES) pressure or function related to:
(a) spontaneous transient LES
relaxations,
(b) transient increases in
intraabdominal pressure, or
(c) an atonic LES

Lower Esophageal Sphincter

GERD may also be caused by the following:

Anatomic factors
Patients with hypotensive LES pressures and large
hiatal hernias are more likely to experience
gastroesophageal reflux following abrupt increases in
intraabdominal pressure compared to patients with a
hypotensive LES and no hiatal hernia.

Esophageal Clearance
Delayed gastric emptying

Complications that may occur with GERD:

Barretts esophagus - refers to an abnormal change in
the cells of the lower portion of theesophagus. It is characterized
by the replacement of the normalstratified squamous
epitheliumlining of the esophagus by simple columnar epithelium
withgoblet cells(which are usually found lower in
thegastrointestinal tract).

Esophageal Adenocarcinoma

Clinical Presentation

Evaluation of Therapeutic Outcomes

relieving symptoms
healing the injured mucosa
preventing complications

Treatment Goals
alleviate or eliminate the patients symptoms
decrease the frequency or recurrence and
duration of gastroesophageal reflux
promote healing of the injured mucosa
prevent the development of complications

Therapeutic Approach
Patient Presentation

Recommended Treatment Regimen

Intermittent, mild heartburn

Lifestyle modification + antacid

Symptomatic relief of GERD

Lifestyle modification + alginatecontaining preparations

C. Scarpignato, G. Gimbo (Parma)

Healing of erosive esophagitis or tx

of px presenting w/ moderate
severe symptoms or complications

An 8-week course of PPIs is the therapy

of choice for symptom relief and
healing of erosive esophagitis. There
are no major differences in efficacy
between the different PPIs. (Strong
recommendation, high level of
evidence)
ACG Guidelines 2013

Interventional therapies

Antireflux surgery or endoscopic

therapies

GERD Treatment Guidelines 2013

Area

Recommendation (Strength/Evidence)

Treatment

Therapy for GERD other than acid suppression, including prokinetic

therapy and/or baclofen, should not be used in GERD patients
without diagnostic evaluation. (Conditional recommendation,
moderate level of evidence)
Bedtime H RA therapy can be added to daytime PPI therapy in
selected patients with objective evidence of night-time reflux if
needed, but may be associated with the development of
tachyphlaxis after several weeks of use. (Conditional
recommendation, low level of evidence)
Maintenance PPI therapy should be administered for GERD patients
who continue to have symptoms after PPI is discontinued, and in
patients with complications including erosive esophagitis and
Barretts esophagus. (Strong recommendation, moderate level of
evidence).

GERD Treatment Guidelines 2013

Area

Recommendation (Strength/Evidence)

Dosing

Traditional delayed release PPIs should be administered 30

60 min before meal for maximal pH control. (Strong
recommendation, moderate level of evidence).
Newer PPIs may offer dosing flexibility relative to meal
timing. (Conditional recommendation, moderate level of
evidence)
PPI therapy should be initiated at once a day dosing,
before the first meal of the day. (Strong recommendation,
moderate level of evidence).
For patients with partial response to once daily therapy,
tailored therapy with adjustment of dose timing and/or
twice daily dosing should be considered in patients with
night-time symptoms, variable schedules, and/or sleep
disturbance. (Strong recommendation, low level of
evidence).
In patients with partial response to PPI therapy, increasing
the dose to twice daily therapy or switching to a different
PPI may provide additional symptom relief. (Conditional
recommendation, low level evidence).

Surgical options for GERD

1. Surgical therapy is a treatment option for long-term therapy in GERD patients.
(Strong recommendation, high level of evidence)
2. Surgical therapy is generally not recommended in patients who do not respond to PPI
therapy. (Strong recommendation, high level of evidence)
3. Preoperative ambulatory pH monitoring is mandatory in patients without evidence of
erosive esophagitis. All patients should undergo preoperative manometry to rule out
achalasia or scleroderma-like esophagus. (Strong recommendation, moderate level of
evidence)
4. Surgical therapy is as effective as medical therapy for carefully selected patients
with chronic GERD when performed by an experienced surgeon. (Strong
recommendation, high level of evidence)
5. Obese patients contemplating surgical therapy for GERD should be considered for
bariatric surgery. Gastric bypass would be the preferred operation in these patients.
(Conditional recommendation, moderate level of evidence)
6. The usage of current endoscopic therapy or transoral incisionless fundoplication
cannot be recommended as an alternative to medical or traditional surgical therapy.
(Strong recommendation, moderate level of evidence)

Lifestyle Modifications
weight loss
elevation of the head of the bed
consumption of smaller meals and not
eating 3 hours prior to sleeping
smoking cessation
avoidance of alcohol

Antacids and Antacid-Alginic Acid Products

Antacids are appropriate in treating mild GERD;
effective for immediate symptomatic relief.
Maintaining the intragastric pH >4 decreases the
activation of pepsinogen topepsin, a proteolytic enzyme.
Neutralization of gastric fluid leads to increased LES
pressure.
Antacid-Alginic Acid products form a highly viscous
solution that floats on the surface of the gastric
contents. This viscous solution is thought to serve as
aprotective barrier for the esophagus against reflux of
gastric contents.

Side Effects:
It may cause gastrointestinal adverse effects
(diarrhea or constipation, depending on the product).
Alterations in mineral metabolism, and acidbase
disturbances.
Aluminum-containing antacids may bind to phosphate
in the gut and lead to bone demineralization.
Antacids have clinically significant drug interactions
with tetracycline, ferrous sulfate, isoniazid,
quinidine, sulfonylureas, and quinolone antibiotics.

H2-Receptor Antagonists
Cimetidine, Famotidine, Nizatidine, and
Ranitidine
block the action ofhistamineat thehistamine
H2receptorsof the parietal cellsin thestomach.
This decreases the production ofstomach acid.
S/E:
headache, somnolence, fatigue, dizziness, and
either constipation or diarrhea.
Cimetidine may inhibit the metabolism of
theophylline, warfarin, phenytoin, nifedipine, and
propranolol.

Proton Pump Inhibitors

superior to H2-receptor antagonists in treating patients with
moderate to severe GERD
decrease gastric acid secretion by inhibiting gastric H+/K+adenosine triphosphatase in gastric parietal cells
produces a profound, long-lasting antisecretory effect capable of
maintaining the gastric pH above 4
S/E:
headache, dizziness, somnolence, diarrhea, constipation, nausea,
and vitamin B12 deficiency
They decrease the absorption of drugs that require an acidic
medium to be absorbed.
Omeprazole has the potential to inhibit the metabolism of
warfarin, diazepam, and phenytoin while lansoprazole may
decrease theophylline concentrations.

PPI Safety Concerns

Risk of Fracture (hip, wrist, spine)
Concern for fractures should not affect decision
to use PPIs except in patients with other known
risk factors for hip fracture. (Conditional/
Moderate)
Patients with osteoporosis can remain on PPIs.
Limit dose and duration.
Ensure adequate Calcium and Vitamin D.
BMD screening if at risk for low bone mass.
Weight bearing exercise recommended.

PPI Safety Concerns

Hypomagnesemia
Re-evaluate need for PPI.
Limit dose and duration.
Consider baseline testing.
Supplementation
C. difficile associated diarrhea (Moderate/Moderate)
Re-evaluate need for PPI.
Limit dose and duration.
Have patients report diarrhea.
Short-term PPI usage may increase the risk of community-acquired pneumonia.
The risk does not appear elevated in long-term users. (Conditional
recommendation, moderate level of evidence)

Promotility Agents
Useful as an adjunct to acid suppression
therapy in patients with a known motility
defect.
Fraught with undesirable side effects and are
not generally as effective as acid suppression
therapy.
Extrapyramidal effects, sedation, and
irritability are common with bethanechol and
metoclopramide.
Cisapride and Bethanechol arent routinely
recommended.