This document discusses GERD (gastroesophageal reflux disease). It provides an overview of GERD including a classification system, symptoms, diagnostic tests like pH monitoring, and subtypes such as erosive esophagitis. Alarm symptoms that may indicate complications are noted. Causes, pathophysiology, and treatment options for various subtypes are reviewed including proton pump inhibitors, prokinetic drugs, treatments for refractory GERD, and the relationship between H. pylori infection and GERD. Newer formulations and potential future treatments are also mentioned.

1. GERD
Dr/ REDA AAMER

6. Gastric contents
pepsin bile acids trypsin
hydrochloric acid
AcidNon acid
impedancemonitoring
pH monitoring

7. Montreal Classification of GERD
From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.

11. ……..

14. The “Richter Scale/Acid Test” to see if
you’re a GERD sufferer or not
1- Do you frequently have one or more of the following:
• a. an uncomfortable feeling behind the breastbone that
seems to be moving upward from the stomach?
• b. a burning sensation in the back of your throat?
• c. a bitter acid taste in your mouth?
2- Do you often experience these problems after meals?
3- Do you experience heartburn or acid indigestion two or more
times per week?
4- Do you find that antacids only provide temporary relief from
your symptoms?
5- Are you taking prescription medication to treat heartburn,
but still having symptoms?
If you
said
yes
to two
or
more
of the
above,American College of Gastroenterology - March 16, 2010
Digestive Disease Specialists Committed to
Quality in Patient Care

17. 1- Dysphagia/odynophagia ( ‫مؤلم‬ ‫)بلع‬
2- Nausea/vomiting
3- Melena, anemia.
4- Weight loss, anorexia
5- Extended duration of symptoms
6- No response to PPI
7- Family history of PUD
8- Caucasian Male, 50+ years old .
Patients with these symptoms are more likely to
have peptic strictures or esophagitis.
Barrett’s esophagus is three to six times more likely
in patients who have had symptoms of GERD for
Alarming Symptoms ( Red Flags):
suggestive of complicated disease include:

18. Heartburn
Endoscopy
Erosive Reflux Disease Non Erosive Reflux Disease
24- h pH monitoring
Functioal Heatburn
+ve-ve
Normal/physiological
acid exposure
NormalAbnormal
NERD

19. Heartburn and normal endoscopy
Functional heartburn - normal /
physiological range of acid exposure
Abnormal acid exposure
Negative
relationship
between symptoms
and acid reflux
events (S1 < 50 %)
Hypersensitive
oesophagus-
positive
relationship
between
symptoms and
acid reflux events
(S1≥ 50%)
Fass, R et al. Gut 2002;51:885-892
Non acid related
stimuli (motor
event, non acid
reflux)
Minute changes
in intra-
oesophagea pH
(pH ≥4)
30% - 50%50% - 70%
60%40%
NERD

20. Clinical features of functional
heartburn
 Absence of regurgitation
 Common overlap syndromes particularly with FD
and IBS
 Common association with psychological
stress.
 Poor response to PPI

21. • A number of mechanisms have been
suggested:--
1- Increased esophageal sensitivity to acid,
2- Non-acid reflux episodes,
3- Increased esophageal mechanosensitivity ,
4- Esophageal motor disorders, or
5- Psychological abnormalities.
Pathophesiology of
Functional heartburn

22. Patient Related factors Therapy related factors
 Compliance
 Motility Disorder
 Eosinophilic Esophagitis
 Hypersensitive Esophagus
 Non-Acidic Reflux
 Psychological Comorbidity
 Eradication of Helicobacter
Pylori infection
 Nocturnal Acid Breakthrough
(NAB)
 Resistance to PPIs
 Rapid Metabolism of PPIs
Causes of Refractory GERD

23. When to suspect?
 Long standing esophageal symptoms
such as dysphagia with or without
food impaction.
 Refractory heartburn on PPIs
 Allergic history
 Peripheral Eosinophilia
 Elevated IgE
Eosinophilic Esophagitis

24. Use of Eosinophilic Density to
Guide Therapy?
No. of eosinophils per HPF
<5 5-20 >20
Consider
aggressive
antireflux Rx
?
Consider Rx for
allergy or primary
eosinophilic
esophagitis
• Identify and eliminate food allergen
• Steroids — systemic, topical

29. GASTROPARESIS

31. Helicobacter pylori and GERD
- Eradication of H. pylori is associated
with mild worsening of GERD in patients
with corpus-predominant gastritis and
improvement in those with antral-
predominant gastritis.
- The standard of care is to eradicate H.
pylori in the context of peptic ulcer
disease.

32. The interaction between GERD and H pylori is complicated
and depends on the type of infection.
- Antral-predominant H pylori infection, which is the most common
type in the United States, is associated with increased acid and
duodenal ulcers and a 2- to 3-fold increased risk of adenocarcinoma.
This type of H pylori can worsen reflux; treating it may improve reflux
symptoms.
- In contrast, studies from Asia where body-predominant H pylori
infection is prevalent show that it protects against Barrett’s
esophagus and adenocarcinoma. Currently, there are no data to
support testing for H pylori in the management of GERD as
eradication should not dramatically alter GERD severity in patients
undergoing treatment.

34. The question of debate and controverse:
Inspite of GERD is a motility disorder and
Gastric acid secretion is normal & pH is > 4
in most of patients with GERD.
The mainstay of treatment is PPIs
(esomepazole ) that mainly inhibit gastric acidity
(HCL) and causticity of gastric juice and not the
prokinetics.

37. Use of H2 blocker in era of PPI
- ON demand therapy.
- NAB.
- REFRACTORY GERD.
- MORE SAFE IN ELDERLY AND
PREGNANCY???.
- IF YOU NEED PROKINETIC : ?NIZATIDINE.

38. Martinez et al., Aliment Pharmacol Ther,.2003
Treatment of Functional Heartburn
Hypersensitive esophagus
Acid sensitive
Non acid related
Minute changes in
intraesophageal (PH> 4)
Non-acid related stimuli
( Motor event)
High dose PPIs
GABA receptor antagonists
High dose PPIs
Tegaserod
Pain modulators

40. The proton
pump
inhibitors
( PPIs )

41. The proton pump inhibitors
( PPIs )
•1- Omeprazole 2- Lansoprazole. 3- Pantoprazole. 4-
Rabeprazole. 5- Esomeprazole.
• PPIs are also prodrugs that are highly
selective to the acidic environment
within the secretory canaliculi of the
gastric parietal cells
substituted
benzimidazoles
• 1- Tenatoprazole.
• 2- Benatoprazole (TU 199)
• - Prolonged plasma half life (7 h.)
• 2-4 fold more potent than omeprazole
Imidazopyridine
derivative
( New PPIs )
• 1- Immediate-release omeprazole
(IR-OME) prowder for oral
suspension
• 2- Immediate-release omeprazole in
a capsule formulation
New
Pharmaceutical
Preparation

42. Important to remember ...
ALL PPIs drugs
Are
Pro Drugs - Weak bases
The absorption takes
place
In
The Upper part of
small Intestine

43. Howden C.W.
New Advances in Immediate Release PPI Therapy, Chicago ; May 17,
2005

45. Binding of PPIs to Proton Pump
cysteine
Drug 321 813 822 892
Omeprazole &
Esomeprazole
- + - +
Lansoprazole + + - +
Pantoprazole &
tenatoprazole
- + + -
Rabeprazole + + - +

46. Patient with hepatic impairement
show a seven fold increase in AUC
for PPIs and aprolonged half life.
Esomeprazole was well tolerated
across the spectrum of hepatic
impairement unlike other PPIs.

48. Katz et al, Am J Med 2000; 108(suppl 4a): 170S-177S.
Symptom Medication and dose Duration
Chest pain PPI b.i.d. 1-8 weeks
Asthma PPI b.i.d. ≤3 month
Cough PPI b.i.d. 1-3 months
Upper airway PPI b.i.d. 1-3 months
Suggested Regimens for
Extra-esophageal Manifestations of GERD

49. With Esomeprazole , more compound is available to inhibit gastric
proton pumps compared with omeprazole
LiverLiver
Esomeprazole
Absorption
Enhanced
delivery to the
proton pump
Metabolites
Advantageous first-pass metabolism decreased
MetabolitesFirst-pass
metabolism
Absorption
Omeprazole

51. Prokinetic (Promotility ) drugs
drugs that enhance the emptying of the stomach and/or gut and enhance the contractions/co-
ordination of the gut. Here is a list of the more common prokinetics in use for treating
gastroparesis and related dysmotilities
• Cisapride (still available under compassionate-release programs)
• Domperidone (Motilium®)
• Metoclopromide .
• Levosulpiride (Levobren®, Levopraid®, available in Italy/Korea)
• Erythromycin (low dosages, not antibiotic dosing levels)
• Tegaserod ( Zelmac®, now only available under special FDA protocols)
• Mosapride Citrate ( available in Asia, SE Asia, South America, and Japan)
• Itopride hydrochloride (Ganaton®, available in Asia, SE Asia, and Japan)
• Renzapride (2008, a Phase III trial in USA has been completed)
• Pruclopride (Resolor®, available in the UK and EU countries)

52. is a prokinetic benzamide derivative unlike
metoclopramide or domperidone. These
drugs inhibit dopamine and have a
gastrokinetic effect.
Itopride is indicated for the treatment of
functional dyspepsia and other gastrointestinal
conditions.
It is a combined D2 receptor antagonist and
acetylcholinesterase inhibitor.
Itopride
(brand name Ganaton)

53. Mosapride
• is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The
major active metabolite of mosapride, known as M1, additionally acts
as a 5HT3 antagonist.which accelerates gastric emptying throughout
the whole of the gastrointestinal tract in humans, and is used for the
treatment of gastritis, gastroesophageal reflux disease, functional
dyspepsia and irritable bowel syndrome. It is recommended to be
taken on an empty stomach (i.e. at least one hour before food or two
hours after food).
• In addition to its prokinetic properties, mosapride also exerts anti-
inflammatory effects on the gastrointestinal tract which may
contribute to some of its therapeutic effects. Mosapride also
promotes neurogenesis in the gastrointestinal tract which may prove
useful in certain bowel disorders. The neurogenesis is due to
mosapride's effect on the 5-HT4 receptor where it acts as an agonist