Download Gastroesophageal Reflux Disease (GERD)

GASTROESOPHAGEAL
REFLUX DISEASE (GERD)
Fall 2014
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 (ie, esophagitis).
GERD should be defined as symptoms or
complications resulting from the reflux of gastric
contents into the esophagus or beyond, into the oral
cavity (including larynx) or lung.
GERD can be further classified as the presence of
symptoms without erosions on endoscopic
examination (non-erosive disease or NERD) or
GERD symptoms with erosions present (ERD).
High Prevalence of Gastroesophageal
Reflux Symptoms
60%
50%
40%
30%
20%
10%
0%
59%
19.8%
Weekly
Monthly
Frequency of heartburn and/or
regurgitation
Locke et al. Gastroenterology 1997;112:1148.
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, 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.
• 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 gastroesophageal 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
•
•
•
•
•
•
Uncertain diagnosis
Atypical symptoms
Symptoms associated with complications
Inadequate response to therapy
Recurrent symptoms
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
well-controlled
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
DOSAGES
DOSAGE
Cimetadine
Tagamet
400mg twice daily
400-800mg twice daily
Famotidine
Pepcid
20mg twice daily
20-40mg twice daily
Nizatidine
Axid
150mg twice daily
150mg twice daily
Ranitidine
zantac
150mg twice daily
150mg twice daily
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
Esomeprazole
Nexium
EQUIVALENT
DOSAGES
40mg daily
DOSAGE
20-40mg daily
Omeprazole
Prilosec
40mg daily
20mg daily
Lansoprazole
Prevacid
30mg daily
15-10md daily
Pantoprazole
Protonix
40mg daily
40mg daily
Rabeprazole
Aciphex
20mg daily
20mg daily
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 gastrooesophageal 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