Download Gastroesophageal Reflux Disease (GERD)

GASTROESOPHAGEAL
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
60%
50%
40%
30%
20%
10%
0%
59%
19.8%
Weekly
Monthly
Frequency of heartburn and/or
regurgitation
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 regurgitation, or spitting up, the
majority (95%) will have abatement of symptoms by 1.0 to 1.5 years of age.
infants with persisting symptoms beyond 2 years of age are at risk of
developing complicated GERD.
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 (10–30
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
Asthma
Aspiration pneumonia
Chronic bronchitis
Pulmonary fibrosis
Other
Chest pain
Dental erosion
ENT
Hoarseness
Laryngitis
Pharyngitis
Chronic cough
Globus sensation
Dysphonia
Sinusitis
Subglottic stenosis
Laryngeal 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:
Stricture (location, length)
Mass (location, length)
Bird’s beak
Hiatal hernia (size, type).
Limitations
Detailed mucosal exam for erosive
esophagitis, Barrett’s esophagus
Endoscopy
Indications for endoscopy
Alarm symptoms
Empiric therapy failure
Preoperative evaluation
Detection of Barrett’s esophagus
Ambulatory 24 hr. pH Monitoring
Physiologic study
Quantify reflux in
proximal/distal esophagus
% time pH < 4
DeMeester 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
Assist placement of 24 hr.
pH catheter
Assess peristalsis
Prior 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:
 Patients with symptoms that are not completely
controlled by PPI therapy can be considered for surgery.
Surgery can also be considered in patients with wellcontrolled gastroesophageal reflux disease (GERD) who
desire definitive, one-time treatment.
 The 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.
 The 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).





Young patients
Poor patient compliance with regard to medications
Postmenopausal women with osteoporosis
Patients with cardiac conduction defects
Cost of medical therapy
Treatment
Antacids
Over the counter acid suppressants
and antacids appropriate initial
therapy
Approx 1/3 of patients with
heartburn-related symptoms use at
least twice weekly
More 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
 Histamine 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.
 Additional H2 blocker therapy has been reported to be useful in
patients with severe disease (particularly those with Barrett esophagus)
who have nocturnal acid breakthrough.
 More effective than placebo and antacids for relieving heartburn in
patients with GERD
 Faster healing of erosive esophagitis when compared with placebo
 Can use regularly or on-demand.
Treatment
AGENT
EQUIVALENT
DOSAGE
DOSAGES
Cimetadine
400mg twice daily
400-800mg twice daily
20mg twice daily
20-40mg twice daily
150mg twice daily
150mg twice daily
150mg twice daily
150mg twice daily
Tagamet
Famotidine
Pepcid
Nizatidine
Axid
Ranitidine
zantac
Treatment: PPI
Proton Pump Inhibitors
Better control of symptoms with PPIs vs H2RAs and better
remission rates
Faster healing of erosive esophagitis with PPIs vs H2RAs
Treatment
AGENT
EQUIVALENT
DOSAGE
DOSAGES
Esomeprazole
40mg daily
20-40mg daily
40mg daily
20mg daily
30mg daily
15-10md daily
40mg daily
40mg daily
20mg daily
20mg daily
Nexium
Omeprazole
Prilosec
Lansoprazole
Prevacid
Pantoprazole
Protonix
Rabeprazole
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
12 week freedom from symptoms
48% vs 77%
12 week healing rate
52% vs 84%
Speed 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
Adjust timing of medication to 15 – 30 minutes before meals
(as opposed to bedtime)
Allows 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 patient’s
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
Barrett’s esophagus
Adenocarcinoma
Erosive Esophagitis
Peptic Stricture
Barium Swallow
Endoscopy
Esophageal Stricture: Dilating Devices
TTS Balloon Dilation of a Peptic Stricture
Barrett’s Esophagus
Esophageal Cancer
Barium Swallow
Endoscopy