1.
Gastroesophageal Reflux Disease
GERD
By
Ahmed Abudeif Abd Elaal
Resident in tropical medicine & gastroenterology department
2009

2.
:Definitions
Gastroesophageal Reflux (GER): Escape of gastric
contents into the esophagus. This process may or may
not produce symptoms.
Reflux esophagitis: Esophageal inflammation caused
by the refluxed material.
Gastroesophageal Reflux Disease (GERD): Any
symptomatic condition or anatomic alteration caused by
the reflux of noxious material from the stomach into the
esophagus.

3.
Pathogenesis of GERD

4.
Pathogenesis of GERD:
A)Antireflux mechanisms.
B) Gastric Factors.
C) Esophageal Clearance Mechanisms.
D) Esophageal Epithelial Resistance.

5.
A) Antireflux Mechanisms:
Normally, there is a positive pressure gradient
between the abdomen and the thorax that tends to
promote the reflux of material from the stomach into
the esophagus. In the absence of effective antireflux
mechanisms this pressure differential would result in
continuous gastroesophageal reflux.

6.
1) Lower Esophageal Sphincter (LES)
It is a 1-3.5 cm segment of specialized circular
muscle in the wall of distal esophagus.
It maintains a resting pressure of 10-45 mmHg
higher than that of the stomach.

7.
Types of LES dysfunction:
1) Intrinsic weakness of the LES muscle:
The resting pressure in the LES remains at or near 0.
Responsible for > 25% of reflux episodes in patients
with severe GERD.
2) Inadequate LES response to increased abdominal
pressure.

8.
3) Transient LES relaxation (TLESR):
Normally, the LES relaxes for 3-10 seconds to allow
the swallowed bolus to enter the stomach.
TLESR is not preceded by swallowing & lasts for up
to 45 seconds.
It is responsible for 70% of reflux episodes in patients
with severe GERD.
Incompetent LES

9.
2) Crural Diaphragm
When the crural diaphragm contract e.g. inspiration
the crurae come together & pinch the distal
esophagus.

10.
3) Anatomic Features:
a) The oblique angle of insertion of the esophagus into
the stomach (angle of His).

11.
b) The circular muscle fibers of the fundus encircle
the lower end of the esophagus.
c) The presence of an intraabdominal segment of the
esophagus.
d) The mucosal rosette of the upper end of the
stomach forming a plug to the lower end of the
esophagus.

12.
B) Gastric Factors:
1) Irritant potency of the refluxed material
Esophageal injury occurs when the refluxed material
is caustic to the esophageal mucosa.
Caustic agents that can be found in the stomach
include acid, pepsin, bile & pancreatic enzymes.

13.
2) Delayed gastric emptying
It causes gastric distention that can stimulate
gastric acid secretion & trigger TLESR.
Causes:
1- Pyloric channel or duodenal ulcers.
2- Mechanical obstruction e.g. by tumour.
3- Neuromuscular abnormalities e.g. DM,
collagen diseases, hypothyroidism, …

14.
C) Esophageal Clearance Mechanisms:
The esophagus is cleared of acid by 4 mechanisms:
1)Gravity.
2) Peristalsis.
3) Salivation.
4) Intrinsic esophageal bicarbonate production.

15.
Impaired esophageal clearance can occur in:
Sleep: due to
1) Elimination of the effect of gravity.
2) Salivation & swallowing cease during sleep
“no peristalsis due to absent swallowing”.
Scleroderma: due to impaired peristalsis.
Cigarette smoking: due to decreased salivation.
Hiatus hernia.

16.
D) Esophageal Epithelial Resistance:
a) Pre-epithelial defenses:
1) Mucous layer:
Acts as a lubricant & a protective barrier against
noxious &irritant luminal contents.
2) Unstirred water layer:
Lies under the mucous layer & its rich in
bicarbonate.
It provides a protective alkaline microenvironment.
b) Post-epithelial defenses.

17.
Diagnosis of GERD

18.
A) Clinical Presentation
1) Heartburn (Pyrosis):
Substernal burning sensation radiating to the chest
sometimes to the throat or the back.
The pain is usually relieved by ingestion of
antacids. within 5 minutes
The pain is aggravated by
- Ingestion of foods that decrease the LES
pressure as chocolate, onions, peppermint, coffee,
tea & foods that have a high content of fat & sugar.

19.
- Ingestion of foods that irritate the esophageal
mucosa directly as spicy foods, citrus products
and tomato products.
- Practices that increase the intraabdominal
pressure e.g. bend over, lift a heavy object,
strain to defecate or run.

20.
2) Regurgitation:
Reflux of sour or bitter material into the mouth
usually at night, when lying down or bending over.
It suggests severe reflux.

21.
3) Dysphagia:
Difficulty in swallowing.
Usually indicates narrowing or stricture of the
esophagus.
It may occur due to inflammation & oedema.

22.
4) Odynophagia:
Pain on swallowing.
It suggests the presence of esophageal
ulceration.

23.
5) Water brash:
Filling of the mouth suddenly with saliva.
Its due to reflex salivary secretion stimulated by
acid in the esophagus.

24.
6) Chest pain:
Resembles anginal pain.
This pain may result from:
• Acid induced irritation of the nerve endings.
• GER-induced esophageal spasm.
• GER-induced angina pectoris.

25.
7) Haemorrhage

26.
8) Pulmonary symptoms:
e.g. chronic cough, hoarseness of voice,
wheezing, haemoptysis, asthma & recurrent
aspiration pneumonia.
The above manifestations may be due to
aspiration or vagus mediated neural reflexes.

27.
9) Nighttime GER may cause:
Sleep apnoea.
Poor sleep.
Insomnia.
Daytime sleepiness.

28.
B) Diagnostic tests:
Indications:
1) Patients with atypical signs or
symptoms.
2) Patients with typical signs &
symptoms that don’t respond well to
acid suppression.

29.
1) Endoscopic examination:
EGD identifies the presence and severity of
esophagitis and the possible presence of
Barrett’s esophagus
More sensitive than radiology for diagnosis of
esophagitis & biopsy can be taken from any
abnormal areas.
Endoscopic evidence of esophagitis is present in
50-70% of patients with typical history of GERD
so a normal EGD (NERD) doesn’t exclude
GERD.

30.
TThhee LLooss AAnnggeelleess CCllaassssiiffiiccaattiioonn SSyysstteemm ffoorr tthhee eennddoossccooppiicc
aasssseessssmmeenntt ooff ggrraaddee ooff eessoopphhaaggiittiiss
GGrraaddee DDeessccrriippttiioonn
AA One or more mucosal breaks no longer than 5 mm, none
of which extends between the tops of the mucosal folds.
BB One or more mucosal breaks more than 5 mm long, none
of which extends between the tops of two mucosal folds.
CC Mucosal breaks that extend between the tops of two or
more mucosal folds, but which involve less than 75% of
the esophageal circumference.
DD Mucosal breaks which involve at least 75% of the
esophageal circumference.

31.
The Los Angeles Classification SSyysstteemm ffoorr tthhee eennddoossccooppiicc
aasssseessssmmeenntt ooff ggrraaddee ooff eessoopphhaaggiittiiss

32.
The Los Angeles Classification SSyysstteemm ffoorr tthhee eennddoossccooppiicc
aasssseessssmmeenntt ooff ggrraaddee ooff eessoopphhaaggiittiiss
GRADE A:
One or more mucosal breaks no
longer than 5 mm, non of which
extends between the tops of
the mucosal folds

33.
TThhee LLooss AAnnggeelleess CCllaassssiiffiiccaattiioonn SSyysstteemm ffoorr tthhee eennddoossccooppiicc
aasssseessssmmeenntt ooff ggrraaddee ooff eessoopphhaaggiittiiss
GGRRAADDEE BB::
OOnnee oorr mmoorree mmuuccoossaall
bbrreeaakkss mmoorree tthhaann 55 mmmm
lloonngg,, nnoonnee ooff wwhhiicchh
eexxtteennddss bbeettwweeeenn tthhee
ttooppss ooff ttwwoo mmuuccoossaall ffoollddss

34.
TThhee LLooss AAnnggeelleess CCllaassssiiffiiccaattiioonn SSyysstteemm ffoorr tthhee eennddoossccooppiicc
aasssseessssmmeenntt ooff ggrraaddee ooff eessoopphhaaggiittiiss
GGRRAADDEE CC::
MMuuccoossaall bbrreeaakkss tthhaatt eexxtteenndd
bbeettwweeeenn tthhee ttooppss ooff ttwwoo oorr
mmoorree mmuuccoossaall ffoollddss,, bbuutt wwhhiicchh
iinnvvoollvvee lleessss tthhaann 7755%% ooff tthhee
ooeessoopphhaaggeeaall cciirrccuummffeerreennccee

35.
TThhee LLooss AAnnggeelleess CCllaassssiiffiiccaattiioonn SSyysstteemm ffoorr tthhee eennddoossccooppiicc
aasssseessssmmeenntt ooff ggrraaddee ooff eessoopphhaaggiittiiss
GGRRAADDEE DD::
MMuuccoossaall bbrreeaakkss wwhhiicchh
iinnvvoollvvee aatt lleeaasstt 7755%% ooff
tthhee ooeessoopphhaaggeeaall
cciirrccuummffeerreennccee

36.
Savary-Miller Classification of esophagitis
Grade I: Single or multiple erosions are found on a single
fold; erosions may be erythematous or exudative.

37.
Savary-Miller Classification of esophagitis
Grade II: Multiple erosions affect multiple folds.

38.
Savary-Miller Classification of esophagitis
Grade III: Multiple circumferential erosions.

39.
Savary-Miller Classification of esophagitis
Grade IV: Ulcer, stricture, and esophageal shortening.

40.
Savary-Miller Classification of esophagitis
Grade V: Barrett’s epithelium.

41.
2) Barium swallow:
Can reveal:
a)Signs of esophagitis including:
1- Thickening of the esophageal folds.
2- Erosions.
3- Ulcerations.
4- Strictures.
b) GER of barium.

42.
Disadvantages:
1) Less sensitive than endoscopy for
demonstrating esophagitis.
2) Biopsy specimens can't be taken.

43.
3) Ambulatory monitoring of esophageal pH:
Its used to document the pattern, frequency &
duration of acid reflux & to seek correlation between
reflux episodes & symptoms.
Normally, esophageal pH remains below 4 for less
than 4.5% of the 24-hour monitoring period.
Acid reflux episode: a drop in esophageal pH
below 4 & the total Reflux episodes exceed 5% of
the total monitoring time.

44.
4) Acid perfusion (Bernstein) test:
It has been used to support acid reflux as the
cause of symptoms.
The esophagus is perfused with 0.1 N HCl.
Reproduction of chest pain with acid perfusion
implicates GERD as a cause of chest pain.

45.
5) Histology:
Histological changes of esophagitis:
1) Lengthening of the papillae so that they occupy
more than 2/3 of the thickness of the squamous
mucosa.
2) Hyperplasia of cells in the basal zone so that it
occupies more than 15% of the mucosal
thickness.
3) Infiltration of the epithelium with eosinophils &
PMNLs.

46.
Treatment of GERD

47.
A)Medical Treatment:
a) Lifestyle Modifications.
b) Pharmacologic Therapy:
1) H2 blockers
2) Proton Pump Inhibitors.
3) Antacids.
4) Prokinetic Drugs.
5) Sucralfate.
B) Antireflux Surgery.
C) Endoscopic Antireflux Procedures.

48.
A)Medical Treatment:
a) Lifestyle Modifications:
1) Elevation of the head of the bed by 4-6 inch
blocks or 6 inch foam-rubber wedge in place of
or under the pillow.
2) Weight loss for obese patients.
- Obesity increase the intraabdominal pressure.

49.
3) Avoid:
a) Smoking
- It decrease LES pressure & salivation.
b) Alcohol
- It decrease LES pressure.
c) Fatty meal, chocolate, onion, tea, coffee &
carminatives.
- They decrease LES pressure & delay gastric
emptying.

50.
d) Spicy foods, citrus & tomato products.
- They cause direct irritation of the esophageal
mucosa.
e) Drugs that decrease LES pressure & delay
gastric emptying as Ca++ channel blockers,
nitrates, drugs that have anticholinergic effects
“e.g. phenothiazines, TCA”, theophylline
preparations, progesterone & benzodiazepines.

51.
4) Encourage small frequent meals, the evening
meal should be light & easy to digest.
5) No eating 3 hours prior to sleep.
- Bed time snacks stimulate gastric acid secretion
& trigger TLESR.

52.
b) Pharmacologic Therapy:
1) H2 Blockers:
These drugs block the effect of histamine on H2
receptors which is present normally in gastric
mucosa, vascular smooth muscle & the heart.
They reduce the basal, food stimulated &
nocturnal secretion of gastric HCl.
Usually effective in controlling symptoms of mild
to moderate GER & heal esophagitis (grade I,II)
within 12 weeks in about ½ to 2/3 of patients.

53.
Drug Indication Dose Duration
Cimetidine - Erosive esophagitis diagnosed
by endoscopy.
- 800 mg BDS
or 400 mg
QDS
- 12 w
Famotidine - Short term ttt of symptoms.
- Esophagitis due to GERD
including erosive or ulcerative
disease diagnosed by endoscopy
- 20 mg BDS
- 20-40 mg
BDS
-6 w
- 12 w
Nizatidine - Esophagitis due to GERD.
including erosive or ulcerative
disease & associated heartburn.
- 150 mg BDS - 12 w
Ranitidine - Treatment of symptoms.
- Esophagitis due to GERD
including erosive or ulcerative
disease diagnosed by endoscopy
-150 mg BDS
- 150 mg QDS
No
limit
specifi
ed

54.
2) Proton Pump Inhibitors (PPIs):
These drugs inhibit parietal cell proton pump (H+
K+ - ATPase).
Proton pump is responsible for extrusion of H+
into the gastric lumen in exchange of K+ which is
the final step in gastric acid production.
PPIs are effective in control of symptoms & signs
of GERD, heal erosive esophagitis & diminish
formation of esophageal strictures.
PPIs improves dysphagia & decrease the need
for esophageal dilatation in patients who have
esophageal strictures.

55.
PPIs are effective if taken 15-30 minutes before
breakfast or dinner.
Drugs of this group include:
- Omeprazole 20 mg - 40 mg.
- Lansoprazole 15 mg – 30 mg.
- Rapeprazole 20 mg.
- Pantoprazole 20 mg – 40 mg.
- Esomeprazole 20 mg – 40 mg.
- Omeprazole NaHCO3 20 mg – 40 mg.

56.
Side effects of PPIs:
- Headache, nausea & vomiting.
- Diarrhoea & Clostridium difficile colitis.
- Theoretically, they may cause gastric bacterial
overgrowth, vitamin B12 & iron malabsorption &
gastric cancer. However, there is no clinical
support.
- Hypocalcaemia (give Ca++ supplements as Ca++
citrate).

57.
3) Antacids:
Antacids may be aluminum, magnesium, or
calcium based
Antacids neutralize the acid in the stomach so
that there is no acid to reflux.
Antacids emptied from the empty stomach
quickly so they should be given an hour after
meal to prolong their duration of action.
Effective in controlling mild symptoms of GERD.

58.
4) Prokinetic Drugs:
These agents act by:
a) Increasing LES pressure.
b) Enhancing gastric & esophageal emptying.
Examples:
1) Metoclopramide HCl.
2) Domperidone.
3) Mosapride citrate.

59.
1) Metoclopramide HCl:
- Dopamine antagonist, centrally acting
antiemetic.
- Its effective in treatment of mild disease.
- It crosses BBB so, it has many central side
effects.
Side effects:
Agitation, restlessness, somnolence, anxiety,
insomnia, extrapyramidal manifestations &
galactorrhoea.

60.
2) Domperidone:
- Dopamine antagonist & produce effects similar
to metoclopramide.
- Unlike metoclopramide it doesn’t cross BBB so
there is no central side effects.

61.
3) Mosapride citrate:
- 5-HT4 receptor agonist & partial 5-HT3
antagonist.
- Unlike cisapride it doesn’t block K+ channels so
no cardiac toxicity will occur, also doesn’t block
D2 receptors, so there is no extrapyramidal
manifestations.

62.
5) Sucralfate:
- An aluminum sucrose polysulfate.
- Effective in treatment of mild reflux esophagitis.
- It is efficacy is comparable to that of H2 blockers.

63.
B) Antireflux Surgery:
There are a number of different antireflux
operations (e.g. Nissen, Belesy, Toupet
fundoplication).
The most popular is Nissen fundoplication (open
or laparoscopic).
Nissen fundoplication

64.
Principle of antireflux surgery:
The surgeon
1) Creates an intraabdominal segment of
esophagus.
2) Reduces the hiatal hernia.
3) Approximates the diaphragmatic crurae.
4) Wraps a portion of gastric fundus around the
distal esophagus.

65.
- There is relief of symptoms & signs in > 85% of
patients.
- Antireflux surgery was associated with a significant
decrease in long term survival so it should be
restricted to:
1) Patients who no longer need to take
antisecretory medications.
2) The procedure will prevent esophageal cancer

66.
C) Endoscopic Antireflux Procedures:
The Bard endoscopic suturing system:
This system uses an endoscopic sewing machine
device to plicate the esophagogastric junction from
the mucosal side.
The Stretta system:
The Stretta system delivers radiofrequency energy
that creates thermal lesions in the LES muscle.
Injection of collagen circumferentially at the LES.

67.
Complications of GERD

68.
1) Esophageal Stricture:
Peptic strictures form when reflux induced ulceration
stimulates fibrous tissue production & collagen
deposition in the esophagus.
Up to 11% of patients with GERD seem to develop
strictures.

69.
Factors predisposing to stricture formation:
- Prolonged GER.
- Reflux while supine.
- Nasogastric intubation.
- Duodenal ulcer disease.
- Gastric hypersecretory states.
- Postgastrectomy states.
- Scleroderma.
- Treated achalasia.

70.
Site of esophageal stricture:
- Usually in the distal 1/3 of the esophagus.
- In some cases of Barrett’s esophagus the stricture
is located in the middle or less commonly in the
proximal 1/3 of the esophagus.

71.
Clinical Picture:
- Esophageal stricture produce no symptoms until
the esophageal intraluminal diameter < 12 mm.
- Typically there is a slowly progressive dysphagia
initially for solids & later on for liquids.
- Profound weight loss is uncommon.

72.
Investigations:
a)Barium Swallow:
- Peptic strictures have a smooth tapered
appearance.
- More sensitive than endoscopy for demonstrating
subtle esophageal narrowing.
b) Endoscopy:
- Endoscopic examination with biopsy & brush
cytology of the esophagus is necessary to exclude
cancer.

73.
Treatment:
- Intensive medical treatment with PPIs both
improves dysphagia & decreases the need for
esophageal dilatation.
- Progressive dilatation with:
• Mercury filled rubber bougies.
• Savary-Gillard dilators.
• Balloons that can be inflated within the stricture.

74.
- Surgical treatment, usually combined with an
antireflux operation.
- Resection with esophageal reconstruction using a
segment of bowel in cases of intractable stricture.

75.
B) Barrett’s Esophagus:
- A condition in which a metaplastic columnar
epithelium replaces squamous epithelium in the
distal esophagus.
- Barrett’s esophagus is a strong risk factor for
adenocarcinoma of the esophagus &
gastroesophageal junction.

76.
- It is usually discovered in middle aged & older
adults. However its found in children as young as 5
years.
- Barrett’s esophagus predominates in white
males. Its uncommon in blacks & asians.

77.
Histology:
Any of 3 types of columnar epithelia can be found
in Barrett’s esophagus.
1) Gastric fundic type epithelium.
2) Junctional type epithelium.
3) Specialized intestinal metaplasia “Specialized
columnar epithelium”.
- Dysplasia & carcinoma are associated with
intestinal metaplasia.

78.
Diagnosis
Clinical Picture:
- The Barrett’s epithelium causes no symptoms.
- Most patients have symptoms of GERD, the
GERD associated with Barrett’s esophagus often is
severe & associated with esophageal ulceration,
stricture & haemorrhage. However, many patients
have no symptoms of GERD.
- Cancer risk is about 0.5% annually.

79.
Endoscopy:
- Columnar epithelium can be recognized by it’s
characteristic red colour & velvet like texture that
contrast sharply with the pale glossy appearance of
the adjacent squamous epithelium.
- According to the length of the lining columnar
epithelium Barrett’s esophagus can be classified
into:
- Short segment Barrett’s esophagus: intestinal
metaplasia lines < 3 cm of the distal esophagus.

80.
- Long segment Barrett’s esophagus: intestinal
metaplasia lines > 3 cm of the distal esophagus.
- Long segment Barrett’s esophagus is associated
with high risk for developing adenocarcinoma.

81.
Management
• Patients with Barrett’s esophagus should
undergo surveillance endoscopy & biopsy at an
interval determined by the presence & grade of
dysplasia:
• For patients with no dysplasia, surveillance
endoscopy is recommended at an interval of every
2-3 years.

82.
• For patients with low grade dysplasia,
surveillance endoscopy every 6 months for the 1st
year is recommended, followed by yearly
endoscopy if the dysplasia hasn’t progressed in
severity.
• For patients with high grade dysplasia 2 options
are available:
1) Intensive endoscopic surveillance until
intramucosal cancer is detected.
2) Esophageal resection.

83.
- GERD should be treated aggressively prior to
surveillance endoscopy to minimize confusion
caused by inflammation in the interpretation of
biopsy specimens.

84.
Refractory GERD

85.
Refractory GERD: patients who continue to have
symptoms of gastroesophageal reflux despite
standard treatment with proton pump inhibitors
(PPIs).
Patients who experience refractory GERD
usually fall into one of two groups:
- Those who need more aggressive treatment
- Those who have other causes of their reflux
symptoms

86.
1) Inadequate response to PPIs

87.
Factors contributing to inadequate PPI
response:
1) Nocturnal Acid Breakthrough (NAB)
2) Reduced bioavailability
3) Effect of food and dosing interval
4) Differences in metabolism
5) Gastric acid hypersecretion
6) Helicobacter pylori status
7) Drug resistance, slow healing

88.
Nocturnal Acid Breakthrough (NAB)
Nocturnal acid exposure while on PPI.
Responsible for majority of patients with refractory
GERD.
May be reduced by H2 blockers and by increasing
PPI dose.
Sometimes difficult to eliminate.

89.
Reduced Bioavailability
Bioavailability of PPI influenced by environmental
and manufacturing conditions.
For most patients, difference in bioavailability are not
clinically significant.

90.
Effect of food and dosing interval
Administration 15-30 min prior to meals improve
gastric acid suppression.
PPI usually given once daily and sometimes twice
daily improve gastric acid suppression.

91.
Differences in metabolism
PPI metabolized through the CYP 2C.
CYP 2C absent:
- 3% of Caucasian patients.
- In more than 10% in Asians.

92.
Gastric acid hypersecretion
Patients with BAO > 10mEq/h may predisposed
to refractory GERD.

93.
Helicobacter pylori status
Role not established in refractory patients.
Helicobacter pylori infection may protect the
esophagus from GERD & its complications
perhaps by decreasing gastric acidity.
No evidence that eradication exacerbates GERD.

94.
Drug Resistance
Resistance is a rare condition caused by mutations
of the proton pump.
Patients can be treated by H2 blockers.

95.
2) Other causes of reflux
symptoms

96.
Other Causes Of Reflux Symptoms:
1) Other pathological situations.
2) Esophageal hypersensitivity.
3) Non acid reflux.

97.
Other Pathological Situation
1) IBS and dyspepsia with overlap syndrome.
2) Atypical GERD (cough, asthma, NCCP).
3) Achalasia.
4) Cancer or stricture.
5) Caustic and Infectious esophagitis.
6) NSAID (more susceptibility to acid related E
disease).

98.
Esophageal Hypersensitivity
There is hypersensitivity to physiologic acid reflux
(visceral hyperalgesia).
Patients have heartburn but without endoscopic or
pH evidence of GERD.
Treatment:
Acid suppressive therapy and low dose
antidepressants

99.
Non Acid Reflux
Mixed acid and bile refluxate (more aggressive than
acid alone).
Duodenogastroesophageal reflux (DGER): in
patients with gastric surgery.

100.
Treatment of Refractory GERD

101.
Medical treatment
-Give PPI twice daily.
-PPI dose before dinner may reduce NAB.
-PPI 15-30 min before meals.
- Stepwise increase dose of PPI to achieve
adequate acid suppression (an increase in dose of
Omeprazole to 80 mg/ day→ significant decrease
in acid secretion (Vs 20 mg bid) (pH <4: 33% Vs
74%).

102.
- Addition of a nighttime dose H2 blockers to control
NAB.
- H2 blockers not as effective as PPI for maintenance
therapy.
- Switching to another PPI for patients refractory to
one PPI ( rare mutations in the PP induce
resistance).
- Effectiveness of adding prokinetic drug not
established.

103.
- Add Baclofen (GABA-B agonist ):
• Effective to treat GERD with chronic cough.
• Inhibits TLESR.
• With Esomeprazole both decrease total acid
and non acid reflux.
Endoscopic treatment
Surgical treatment