GASTROESOPHAGE

AL REFLUX
DISEASE (GERD)

Summer 2013
Gastroesophageal Reflux
Disease (GERD)
Gastroesophageal reflux (GER) is defined as the
retrograde passage of gastric contents from the
stomach into the esophagus. It is primarily the result
of transient relaxation of the LES.

Gastroesophageal reflux is a normal physiologic

phenomenon experienced intermittently by most
people, particularly after a meal.
Gastroesophageal reflux disease (GERD) occurs
when the amount of gastric juice that refluxes into the
esophagus exceeds the normal limit, causing
symptoms with or without associated esophageal
mucosal injury (i.e., esophagitis).
High Prevalence of
Gastroesophageal Reflux
Symptoms
 Epidemiology
GERD is a chronic disease that affects patients across all age
groups with equal distribution between men and women. The
prevalence of GERD appears to be greater in the Western
population with patients presenting with more clinically
important disease and complications than in Eastern
countries (especially Asian populations) where GERD is
uncommon.

It has also been estimated that 7% of the U.S. population

have complicated GERD associated with erosive esophagitis.

Up to 75% of patients who undergo endoscopic procedures

due to symptoms associated with GERD have normal
esophageal findings. These patients are identified as having
functional heartburn, (nonerosive reflux disease) NERD, or
endoscopy-negative reflux disease (ENRD).

Childhood GERD appears to continue into adolescence and

adulthood. Although most infants develop physiological
Epidemiology
Complications associated with GERD include esophageal
erosions (5%), strictures (4%20%), and Barrett's metaplasia
(8%20%).
Male gender and advancing age (men and women) are
associated with an increase in the prevalence of esophageal
complications, presumably due to refluxed acidic contents
damaging the mucosa over time. No sexual predilection exists.

The prevalence of GERD increases in people older than 40 years.

Approximately 50% of patients with gastric reflux develop

esophagitis.
Pathophysiology
Abnormal gastro-esophageal reflux is caused by the
abnormalities of one or more of the following protective
mechanisms:
1) Transient Relaxations of the Lower Esophageal Sphincter.
The LES, when in a resting state, remains at a high pressure
(1030 mmHg) to prevent the gastric contents from entering
into the esophagus.
Pressures are lowest during the day and with meals and
highest at night.
Transient relaxations of the LES are short periods of
sphincter relaxation that are different from those that occur
with swallowing or peristalsis. They occur due to vagal
stimulation in response to gastric distension from meals
(most common), gas, stress, vomiting, or coughing and can
persist >10 seconds. These transient relaxations of the LES
are associated with virtually all GER events in healthy
individuals but account for 50% to 80% of occurrences in
patients with pathogenic GERD
2) Esophageal Acid Clearance and Buffering
Capabilities.

Peristalsis is the primary mechanism by which acid refluxate is

removed from the esophagus. Other mechanisms include
swallowing, esophageal distension in response to refluxate, and
gravity (which is only effective when the patient is in an upright
position).

Saliva plays an important role in the neutralization of gastric acid

within the esophagus. Its bicarbonate-rich content buffers the
residual acid that remains in the esophagus after peristalsis

The reduction of swallowing that occurs during sleep is

associated with nocturnal GERD. Patients with decreased saliva
production (e.g., elderly, patients taking medication with
anticholinergic effects, and those with certain medication
conditions such as xerostomia or Sjogren's syndrome) may also
be at increased risk of developing GERD
3) Anatomic Abnormalities.

4) Gastric Emptying

5) Mucosal Resistance

6) Aggressive Factors Associated With

Esophageal Damage
Clinical Presentations of
GERD

Classic (Typical) GERD

Extraesophageal (Atypical)
GERD
Complicated GERD
Extraesophageal
Manifestations of GERD
Pulmonary ENT
A
sthma oarseness
A
aryngitis
spiration pneumonia
haryngitis C
hronic bronchitis
hronic cough P
ulmonary fibrosis
lobus sensation

ysphonia

Other inusitis

Chest pain ubglottic stenosis

Dental erosion aryngeal cancer

 Potential Oral and Laryngopharyngeal
Signs Associated with GERD

Edema and hyperemia of

larynx
Vocal cord erythema,
polyps, granulomas,
ulcers
Hyperemia and lymphoid
hyperplasia of posterior
pharynx
Interarytenyoid changes
Dental erosion
Subglottic stenosis
Laryngeal cancer
Vaezi MF, Hicks DM, Abelson TI, Richter JE. Clin Gastro Hep 2003;1:333-344.
Gastroesophageal reflux disease (GERD) can
cause typical (esophageal) symptoms or
atypical (extraesophageal) symptoms.
However, a diagnosis of gastroesophageal reflux
disease (GERD) based on the presence of typical
symptoms is correct in only 70% of patients.

Therefore, GERD cannot be confirmed

solely based on clinical symptoms.
When to Perform
Diagnostic Tests
1. Uncertain diagnosis
2. Atypical symptoms
3. Symptoms associated with complications
4. Inadequate response to therapy
5. Recurrent symptoms
6. Prior to anti-reflux surgery
Diagnostic Tests for
GERD
Barium swallow
Endoscopy
Ambulatory pH monitoring
Esophageal manometry
Barium Swallow
A
barium esophagogram is particularly important
for patients with gastroesophageal reflux disease
(GERD) who experience dysphagia due to:

S
tricture (location, length)
M
ass (location, length)
B
irds beak
H
iatal hernia (size, type).

Limitations
D
etailed mucosal exam for erosive esophagitis,
Barretts esophagus
Endoscopy

Indications for endoscopy

larm symptoms

mpiric therapy failure

reoperative evaluation

etection of Barretts esophagus

Ambulatory 24 hr. pH
Monitoring
Physiologic study
Quantify reflux in
proximal/distal esophagus

time pH < 4

eMeester score
Symptom
correlation
 Ambulatory 24 hr. pH Monitoring

Normal

GERD
Wireless, Catheter-Free Esophageal pH
Monitoring
Potential Advantages

Improved patient
comfort and acceptance
Continued normal work,
activities and diet study
Longer reporting periods
possible (48 hours)
Maintain constant probe
position relative to SCJ
Esophageal Manometry

Limited role in GERD

Assess LES pressure,

location and relaxation

ssist placement of 24 hr.

pH catheter
Assess peristalsis

rior to antireflux surgery

Treatment Goals for
GERD
Eliminate symptoms
Heal esophagitis
Manage or prevent complications
Maintain remission
Step-wise progression of GERD
therapy

Phase I: Mild/occasional symptoms. Do not seek

medical help.

Phase II a: Persistent symptoms, mucosal damage.

Phase II b: Severe mucosal damage.

Phase III: Refractory disease.

The following table summarizes the pharmacologic

treatments for the different phases.
Phase II a: Persistent symptoms, mucosal
damage.
Cimitidine 400 mg bid, ranitidine 150 mg bid,
famotidine 20 mg bid, nizatidine 150 mg bid.
Metoclopramide 10-20 mg ac and HS

Phase II b: severe mucosal damage.

Cimitidine 800 mg bid or 400 mg qid, ranitidine
150 mg qid, famotidine 40 mg bid, nizatidine 150
mg qid
Metoclopramide 10-20 mg ac and HS
PPI
Phase III: refractory disease. Anti-reflux surgery.
PPI bid for a short period of time. If no
improvement, consider surgery.

Approximately 80% of patients have a recurrent

but nonprogressive form of gastroesophageal reflux
disease (GERD) that is controlled with medications.
Identifying the 20% of patients who have a
progressive form of the disease is important,
because they may develop severe complications,
such as strictures or Barrett esophagus. For
patients who develop complications, surgical
treatment should be considered at an earlier stage
to avoid the sequelae of the disease that can have
serious consequences.
 Indications for fundoplication
include the following:
P
atients with symptoms that are not completely
controlled by PPI therapy can be considered for
surgery. Surgery can also be considered in patients
with well-controlled gastroesophageal reflux
disease (GERD) who desire definitive, one-time
treatment.

T
he presence of Barrett esophagus is an indication
for surgery. Whether acid suppression improves
the outcome or prevents the progression of Barrett
esophagus remains unknown, but most authorities
recommend complete acid suppression in patients
with histologically proven Barrett esophagus.

he presence of extraesophageal manifestations of
gastroesophageal reflux disease (GERD) may indicate
the need for surgery. These include the following: (1)
respiratory manifestations (eg, cough, wheezing,
aspiration); (2) ear, nose, and throat manifestations
(eg, hoarseness, sore throat, otitis media); and (3)
dental manifestations (eg, enamel erosion).

oung patients

oor patient compliance with regard to medications

ostmenopausal women with osteoporosis

atients with cardiac conduction defects

ost of medical therapy
Treatment Antacids

ver the counter acid

suppressants and antacids
appropriate initial therapy

pprox 1/3 of patients with

heartburn-related symptoms
use at least twice weekly

ore effective than placebo in

relieving GERD symptoms
Antacids: work within 5-15 minutes. Duration of
relief 1-3 hours. An adult dose is about 40-80 mEq
acid-neutralizing capacity (ANC) taken 4-5 times
daily.
Sodium Bicarbonate
Calcium Carbonate
Aluminum Hydroxide
Magnesium Hydroxide
Magnesium-Aluminum Hydroxides
Possible interactions with tetracyclines, quinolone
antibiotics, iron supplements, digoxin,
azithromycin.
Alginic acid: works by forming sodium alginate
which is a viscous solution that floats on the
surface of gastric contents so that when reflux
occurs, sodium alginate rather than acid is
refluxed and irritation is minimized.
Tablets should be chewed and taken with a full
glass of water.
Should be taken when patients are in an upright
position. NOT at bedtime.
Common Alginic Acid
Products
Treatment: H-2 Blockers H
istamine H2-receptor antagonists are the first-line agents for
patients with mild to moderate symptoms and grades I-II
esophagitis. Histamine H2 receptor antagonists are effective for
healing only mild esophagitis in 70-80% of patients with
gastroesophageal reflux disease (GERD) and for providing
maintenance therapy to prevent relapse. Tachyphylaxis has
been observed, suggesting that pharmacologic tolerance
can reduce the long-term efficacy of these drugs.

A
dditional H2 blocker therapy has been reported to be useful in
patients with severe disease (particularly those with Barrett
esophagus) who have nocturnal acid breakthrough.

M
ore effective than placebo and antacids for relieving heartburn in
patients with GERD
F
aster healing of erosive esophagitis when compared with placebo
C
an use regularly or on-demand.
Treatment
AGENT EQUIVALENT DOSAGE
DOSAGES
Cimetadine 400mg twice daily 400-800mg twice daily

Tagamet

Famotidine 20mg twice daily 20-40mg twice daily

Pepcid

Nizatidine 150mg twice daily 150mg twice daily

Axid

Ranitidine 150mg twice daily 150mg twice daily

zantac
Treatment: PPI
Proton Pump Inhibitors

etter control of symptoms with PPIs vs H2RAs

and better remission rates

aster healing of erosive esophagitis with PPIs vs

H2RAs
 Treatment
AGENT EQUIVALENT DOSAGE
DOSAGES
Esomeprazole 40mg daily 20-40mg daily
Nexium

Omeprazole 40mg daily 20mg daily

Prilosec

Lansoprazole 30mg daily 15-10md daily

Prevacid

Pantoprazole 40mg daily 40mg daily

Protonix

Rabeprazole 20mg daily 20mg daily

Aciphex
Newest PPI on the market

Dexlansoprazole (trade names

Kapidex, Dexilant) is a proton pump
inhibitor that is marketed by Takeda
Pharmaceuticals. Chemically, it is an
enantiomer of lansoprazole. The
compound was launched in the US for
use in the treatment and maintenance
of patients with erosive oesophagitis
and non-erosive gastro-oesophageal
reflux disease. Dexlansoprazole was
approved by the U.S. Food and Drug
Administration (FDA) on January 30,
2009
 OTC PPI Products
OTC PPI strengths and dosage forms:

Omeprazole 20 mg delayed release tablets.

Omeprazole and sodium bicarbonate 20/1100 mg immediate release capsules.
Lansoprazole 15 mg delayed release capsules.
Treatment
H2RAs vs PPIs

2 week freedom from symptoms

48% vs 77%

2 week healing rate

52% vs 84%

peed of healing
6%/wk vs 12%/wk
Effectiveness of Medical
Therapies for GERD
Treatment Response

Lifestyle modifications/antacids 20 %

H2-receptor antagonists 50 %

Single-dose PPI 80 %

Increased-dose PPI up to 100 %

 Summary of Treatment Algorithm for GERD

Figure 26-5 Management of gastroesophageal reflux disease. H2RA, H2-

receptor antagonist; PPI, proton pump inhibitor.
If Initial Treatment Fails, the Following
Should be Considered:

Improve compliance

Optimize pharmacokinetics

djust timing of medication to 15 30 minutes

before meals (as opposed to bedtime)

llows for high blood level to interact with parietal

cell proton pump activated by the meal

Consider switching to a different PPI

GERD is a Chronic Relapsing
Condition

Esophagitis relapses quickly after cessation of

therapy

50 % relapse within 2 months

80 % relapse within 6 months

Effective maintenance therapy is imperative
 Brain Storming! (2-slides)
Can PPIs be co-adminstered with
antacids / H2 blockers? What should
be the patients instructions?

Why is omperazole 10 mg capsules

Rx only while 20 mg tablets is OTC?

Since 95% of the proton pumps will

be permanently inactivated within 5
days of single daily use of a full-dose
PPI, what is the rationale for twice
daily dosing?
Several weeks after daily dosing of a PPI,
patients usually complain of breakthrough
heartburns. Why is that? How can this be
managed?
A patient did not get a full relief with
omeprazole 40 mg daily. Should we increase the
dose to 80 mg or change into another PPI?
What are the main differences in indications
and use instructions between OTC and Rx PPI
products?
Complications of GERD
Erosive/ulcerative esophagitis

Esophageal (peptic) stricture

Barretts esophagus

Adenocarcinoma
Erosive Esophagitis
 Peptic Stricture

Barium Swallow Endoscopy

Esophageal Stricture: Dilating Devices
TTS Balloon Dilation of a Peptic Stricture
Barretts Esophagus
 Esophageal Cancer

Barium Swallow Endoscopy