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Gastroesophageal Reflux Disease
(GERD)
Questions & Answers
Iranian College of Internal Medicine
Hamid Kalantari MD
Professor of Gastroenterology
Isfahan University of Medical Sciences
Gastroesophageal reflux
goes by several names:
• GERD
• Reflux
• Heartburn
• Indigestion
Definition of GERD
• When the reflux of gastric content causes
troublesome symptoms or complications.
Diagnosis
• GERD presents with typical signs and symptoms,
such as heartburn or acid regurgitation, that are
responsive to antisecretory therapy.
Montreal classification of GERD
Who should have endoscopy?
• Individuals who:
 Fail to respond to therapy.
 Have alarm symptoms or signs such as:
dysphagia, weight loss, anemia, gastrointestinal
bleeding, persistent heartburn.
 Require continuous maintenance medical therapy to
rule out Barrett's esophagus.
What are the goals of endoscopy?
• Detection of erosive esophagitis.
• Complications such as:
 Peptic stricture
 Barrett's esophagus and cancer of esophagus.
• Excludes conditions that can mimic GERD,
such as eosinophilic esophagitis.
Nonerosive gastroesophageal
reflux disease (NERD)
• The majority of patients with typical symptoms
of GERD do not have esophagitis.
NERD
A. Normal levels of esophageal acid:
Esophageal hypersensitivity
– Assessed by a 24-hour pH monitoring study.
B. Abnormal levels of esophageal acid.
C. heartburn not attributable to acid reflux:
“Functional heartburn"
– Groups (A, B), but not the Group C may respond to antisecretory
therapy.
– Proton pump inhibitors were associated with more effective symptom
relief than placebo or H2 receptor antagonists in such patients
Treatment of esophageal
hypersensitivity
• Pain modulators such as:
 Tricyclic antidepressants
 Trazodone
 Selective serotonin reuptake inhibitors
(Improve esophageal pain in patients with noncardiac chest
pain (by acting at the central nervous system and/or sensory
afferents level)
Can I have GERD without
any symptoms?
Yes, GERD can occur with "silent" symptoms.
Silent GERD
Silent GERD" is one of the most difficult
conditions to diagnose
• Sleep disruption (A diagnosis of GERD with
complaints of difficulty sleeping)
• Persistent cough
• Asthma attacks
• Hoarseness
• Dental erosions (may be the first symptom)
• Bad breath
• Water brash
Is there a difference between
day time and night time GERD?
• The major difference between day and
night GERD management is in your
body position.
Can GERD cause
changes in my voice?
• Repeated acid damage of the voice box
can cause growths (polyps) to develop
and can increase your risk of cancer.
What are alarm signs of GERD?(1)
• Do you experience GERD or heartburn 3 or more
times per week?
• Is the pain in your chest from heartburn or reflux
debilitating?
• Does the pain radiate to your arm or cause you to
become short of breath?
• Does the pain wake you from sleep or prevent you
from getting a full night's rest?
What are alarm signs of GERD?(2)
• Have these symptoms been ongoing for more than
6 months?
• Do you have a persistent and unexplained cough?
• Is your asthma difficult to control with conventional
medications?
• Has the reflux caused you to lose weight over the
past few months?
What are alarm signs of GERD?(3)
• Do you have pain after you eat?
• Do you have any difficulty swallowing?
• Do you wake up from sleep coughing, choking,
or short of breath?
• Do you have unexplained repeated episodes of
bronchitis or pneumonia?
Pregnancy & GERD
• Lifestyle modifications or antacids should be
first-line therapy.
• H2 receptor antagonists ranitidine and cimetidine,
which appear to be safe during pregnancy.
• Proton pump inhibitors. (Less experience)
No significant difference in the risk for major
congenital birth defects, spontaneous abortions, or
preterm delivery.
Do children get GERD?
Infants may exhibit symptoms different from adults
• Irritable after eating
• Repeatedly belch or vomit
• Persistent coughing
 Poor feeding
 Impaired weight gain
or colic or
Does GERD affect one gender
more than the other?
Females
are slightly more affected by GERD
Can GERD happened out of
patient’s control?
• Factors out of a patient's control include:
– Genetics
– Personal background
How can I improve
my symptoms of GERD?
How can I improve
my symptoms of GERD?
• Mild symptoms: lifestyle and dietary modifications along
with antacids and histamine-2 (H2) receptor antagonists.
• Debilitating symptoms: acid-suppressive therapy.
• Between these extremes:
 “Step up" approach.
 “Step down" approach.
Lifestyle modifications
Aims of Lifestyle modifications
• Enhancing esophageal acid clearance.
• Minimizing the incidence of reflux.
Does my bed make a difference
in nighttime symptoms?
Head of bed elevation:
• 6- to 8-inch (it is important for individuals with nocturnal
or laryngeal symptoms).
Night symptoms:
• Heartburn
• Regurgitation with coughing, aspiration and pneumonia
• Choking
• Gasping for air
• Bitter taste in your mouth or excessive drooling
What kind of foods can
make GERD worse?
• High-fat foods
• Alcohol
• Spicy foods
• Colas
• Carbonated beverages
• Red wine
• Chocolate
• Orange juice
• Mint
What kind of foods should I eat
if I Have GERD?
• Smaller and lighter meals
• Most food and vegetables
• High protein diet
• Low fat diet
Foods can make GERD worse
(Mechanism)
Reduce lower esophageal sphincter pressure:
• Fatty foods
• Chocolate
• Peppermint
• Excessive alcohol
Acidic pH can exacerbate symptoms:
A number of beverages include:
• Colas
• Red wine
• Orange juice (pH 2.5 to 3.9).
Can smoking cause GERD?
Smoking does not directly cause GERD,
it can exacerbate GERD symptoms.
Smoking is deleterious in part because it
diminishes salivation.
Promotion of salivation by either chewing
gum or use of oral lozenges.
Can stress increase GERD
symptoms?
• Some people do experience heartburn in times
of stress.
• Stress hormones cause stomach relaxation
• Stress hormones may increase stomach acid
production.
Can medicines exacerbate GERD?
• Relaxes the LES of the esophagus.
• Irritates and directly damages the lining of the
esophagus.
• Can cause the body's digestive system to slow down,
which leads to food lingering in and more acid
production in the stomach.
Medications that May Cause
Reflux or Heartburn(1)
Medication (generic)
Medication (trade)
Uses
Amitriptyline
Elavil
Antidepressant medication
Diazepam
Valium
Antianxiety
Diltiazem
Cardizem, Cartia, Tiazac
Calcium channel
blocker-High blood pressure
Doxepin
Sinequan
Antidepressant medication
Felodipine
Plendil
Calcium channel
blocker-High blood pressure
Imipramine
Tofranil
Antidepressant medication
Isosorbide nitrate
Imdur, Nitrodur
Nitrates-High blood
pressure or angina
Medications that May Cause
Reflux or Heartburn(2)
Medication (generic)
Medication (trade)
Uses
Labetalol
n/a
Beta-Blocker-High blood pressure
Levodopa
Sinemet
Anti-Parkinsons
Nifedipine
Adalat, Procardia
Calcium channel
blocker-High blood pressure
Nortriptyline
Aventyl, Pamelor
Antidepressant medication
Progestin
n/a
Birth control or abnormal menstmal
bleeding
Theophylline
Theolair, Uniphyl
AntiAsthma
Mctoprolol
Toprol
Beta blocker-High
blood pressure
Medications that can Cause Direct Damage
to the Esophagus Medication (1)
Medication (generic)
Medication (trade)
Uses
Alendronate
Fosomax
Osteoporosis Medication
Aspirin
Anti-inflammatory
Azithromycin
Zithromax
Antibiotic
Clarithromycin
Biaxin
Antibiotic
Erythromycin
E-mycin
Antibiotic
Ibuprofen
Advil, Motrin
Anti-inflammatory
Medications that can Cause Direct Damage
to the Esophagus Medication (2)
Medication (generic)
Medication (trade)
Iron
Uses
Mineral supplementation
Naproxen
Aleve, Naprosyn
Anti-inflammatory
Potassium
K-Dur
Mineral supplementation
Quinidine
Duraquin
Heart rate medication
Risedronate
Actonel
Osteoporosis medication
Tertracycline
Sumycin
Antibiotic
Vitamin C
Vitamins
How can I avoid GERD problems
if I have to take my pills?
Can exercise affect my reflux?
Does GERD get worse with age?
Can my weight affect my GERD?
Obesity
Risk factor for:
• GERD
• Erosive esophagitis
• Esophageal adenocarcinoma
Aims of Acid-Suppressive
Medications:
Reduce gastric acid secretion
The goal being to raise the intragastric pH above 4
Reduce gastric acid secretion
• The most common and effective treatment
of peptic esophagitis or symptomatic GERD:
– H2 blocker
– Proton pump inhibitor
These therapies do not prevent reflux, but they reduce the
acidity of the refluxate.
Therapeutic gain relative to the
placebo for healing esophagitis
• The H2 receptor antagonists: 10 to 24 percent.
• The proton pump inhibitors: 57 to 74 percent.
Complete relief from heartburn per week
• Proton pump inhibitor (11.5 percent).
• H2 receptor antagonist (6.4 percent).
Acid-suppressive Medications
H2 receptor antagonists:
• Cimetidine (Tagamet)
• Ranitidine (Zantac)
• Famotidine (Pepcid)
• Nizatidine (Axid)
What do you do?
• Patients who continue to have heartburn
after six weeks of treatment with a
standard dose of an H2 antagonist.
Proton Pump Inhibitors
Mode of action of proton pump
inhibitors (PPIs)

PPI inhibit H+/K+-ATPase in the
secretory canaliculi of the
stimulated parietal cell, thereby
blocking the final common
pathway of gastric acid secretion
What are the different proton
pump inhibitors?
How should they be taken?
Proton pump inhibitors
Drug
Dose (adult) oral
Omeprazole
20 mg/ day; maintenance dose, 20 mg/ day
Lansoprazole
30 mg/ day; maintenance dose, 15 mg/ day
Pantoprazole
40 mg/ day; maintenance dose, 40 mg/ day
Rabeprazole
20 mg/ day; maintenance dose, 20 mg/ day
Esomeprazole
20-40 mg/day; maintenance dose, 20 mg/day
Dexlansoprazole
30-60 mg/day; maintenance dose, 30 mg/day
Binding sites of different PPIs on the
proton pump
Cys 822 is the unique additional binding site for Pantoprazole only
Cys 813
Cys 822
Cys 321

Pantoprazole
Omeprazole


Esomeprazole


Lansoprazole

Rabeprazole

= Binding
 = No binding

No reactivation of ATPase activity by
reducing agents after proton pump
inhibition by Pantoprazole
% reactivation of
ATPase activity*
H+K+- ATPase activity after Pantoprazole treatment depends entirely on de
novo synthesis of pump
100
90
80
70
60
50
40
30
20
10
0
100
100
100
Omeprazole
Esomeprazole
Rabeprazole
Lansoprazole
Pantoprazole
70
0
*After 1 hour incubation with DTT (dithiotreitol) or GSH (glutathione) single oral doses (mg)
100
Pantoprazole
Omeprazole
Lansoprazole
Rabeprazole
50
Cytosol
Lysosomes
Parietal cell
Activated PPI after 1 hour (%)
Activation of PPIs as a function of pH
0
1
3
5
7
pH
Pharmacokinetic comparison of five PPIs
Pantoprazole shows a significantly higher AUC in
comparison to other PPIs
Concentration (uMol/L)
7.0
6.5
6.0
Pantoprazole 40mg
5.5
5.0
4.5
Omeprazole 20mg
Esomeprazole 40mg
4.0
3.5
Esomeprazole 20mg
3.0
Rabeprazole 20mg
2.5
2.0
1.5
Lansoprazole 30mg
1.0
0.5
0.0
0
2
4
6
8
10
12
14
Hours after dose
16
18
20
22
24
Do I need to take the
medication every day or just
when I have reflux?
What is Barrett’s Esophagus?
The normal squamous epithelium is
replaced by columnar epithelium.
Will I get cancer from having
Barrett’s esophagus?
What can be done to make
Barrett’s esophagus better or
make it go away?
If I have Barrett’s esophagus,
does it need to be followed?
Treatment algorithm for
patients Barrett’s
esophagus.
Refractory GERD
The definition of "refractory" GERD is unsettled.
• Lack of a clinical response to:
A PPI given one or twice daily.
Differential diagnosis
• Nonerosive gastroesophageal reflux disease (NERD)
• Achalasia
• Esophageal cancer
• Esophageal stricture
• Other causes of esophagitis (NSAIDS, Pills, Caustic
ingestion, Candida, herpes, radiation)
• Gastric stasis
• Sensitization to foods
Refractory GERD
• Most patients with GERD who do not respond
to a PPI have nonerosive reflux disease
(NERD) or functional heartburn.
Treatment of refractory GERD
• Reinforcement of lifestyle modification.
• Switching to another PPI or doubling the PPI dose
(divided at morning and at night before meal).
 We usually double the dose for eight weeks
before considering an alternative PPI.
Adjunctive therapy
Prokinetic drugs
• Prokinetic agents
• Bethanechol
• Metoclopramide
• Domperidone
Mechanisms
• Increasing lower esophageal sphincter pressure
• Enhancing gastric emptying, or improving peristalsis.
Treatment of helicobacter pylori
&
GERD
• Antrum-predominant gastritis (hypersecretors)
• Corpus-predominant gastritis (hyposecretors)
Chronic GERD
• Symptoms occurring in three or more
episodes a week for 6 months or longer.
If my GERD is chronic and
possibly lifelong, do I need to take
medications for life or are there
any other options?
If my symptoms get better,
can I stop taking medication?
Maintenance therapy
It is determined by the rapidity of recurrence.
• Recurrent symptoms in less than three months suggest
disease best managed with continuous therapy.
• Recurrences occurring after more than three months
can be managed by repeated courses of acute therapy
as necessary.
PPIs at a standard dose is recommended.
Intermittent therapy
• Intermittent (on-demand) therapy with an
H2 receptor antagonist or proton pump
inhibitor may be successful in some patients
with mild to moderate heartburn without
moderate or severe esophagitis.
Safety of Medications
• Hypergastrinemia
• Pneumonia
• Hypergastrinemia
• Atrophic gastritis
• Enteric infections
• Vitamin B12 malabsorption
• Hip fracture and calcium malabsorption
• Magnesium absorption
Bedtime H2 receptor antagonist
• Only in patients who failed PPI twice daily.
• In patients with persistent acid reflux after the
addition of an H2RA, antacids (eg, aluminum
hydroxide, magnesium hydroxide) or sucralfate
may provide some relief
Reducing weakly acidic reflux
• Baclofen, a gamma-aminobutyric acid B receptor
agonist, was introduced as a potential add-on
treatment for patients who failed PPI treatment
(once or twice daily).
• The drug reduced TLESR rate by 40 to 60 percent,
reduced reflux episodes by 43 percent, increased
lower esophageal sphincter basal pressure, and
accelerated gastric emptying.
Reducing weakly acidic reflux (cont.)
• In patients with persistent heartburn despite PPI
treatment, doses up to 20 mg three times daily
have been used.
• CNS related side effects: (Somnolence, confusion,
dizziness, lightheadedness, drowsiness,
weakness, and trembling)
Reducing weakly acidic reflux (cont.)
• We usually begin by giving 10 mg twice daily,
which can be increased slowly to 20 mg
three times daily while carefully monitoring
for side effects.
Esophageal pH testing
• Patients who fail PPI twice daily.
• While off treatment to determine if reflux is the cause
of their symptoms.
• While on treatment to determine if there is continued
pathological acid exposure despite a PPI.
Esophageal Manometry
• Suspected achalasia, esophageal manometry
should be considered.
• The value of esophageal manometry in refractory
GERD is very limited.
• This is primarily because most of treatment failure
patients have NERD or functional heartburn.
Management of heartburn or
regurgitation symptoms
What should I do if the
medication is not working?
Should I have surgery
for my GERD?
Preoperative GERD evaluation:
The most useful tests in making surgical decisions:
• Upper endoscopy
• Esophageal manometry
• Assessment of esophageal length
• Degree of hiatal herniation
Indications for operation of
GERD
• Gastrointestinal indications
• Non Gastrointestinal indications
Gastrointestinal indications:
• Failed optimal medical management
• Noncompliance with medical therapy
• High volume reflux
• Severe esophagitis by endoscopy
• Benign stricture
• Barrett's columnar-lined epithelium (without
severe dysplasia or carcinoma)
Non Gastrointestinal indications
About one-half of patients with GERD report upper
respiratory symptoms including:
• Cough (the most common extraesophageal symptoms)
• Hoarseness
• Laryngitis
• Wheezing
• Nocturnal asthma
• Aspiration
• Dental erosion
Fundoplication
• Antireflux surgery should be considered in patients
who require high doses of proton pump inhibitors to
control symptoms, particularly in young patients
who may require lifelong therapy.
Conclusions
Thanks for your
attention