2. Rabe. 20
We will discuss
 GI system
 Acid secretion process
 Acid related disorders
 Treatment options & limitations
 Rabeprazole

4. The Stomach

5. The Stomach
Stomach consists of 3 parts viz. Fundus, Body
and Antrum. Stomach is the part of the GIT,
which produces Hydrochloric acid.
Functions of HCl are
1.Destroying the bacteria present in the food
2.Chemical breakdown of food
3.Activation of digestive enzyme
pepsin

6. The Stomach
FUNDUS: Food enters the upper section of the
stomach, called the FUNDUS.
Contains rugae folds to help with expansion when food
enters stomach, which the main function of the fundus.
BODY: It is the middle part of the stomach, which
follows after fundus. Food remains here for some
time, mixes with gastric juices and then forwarded to
the antrum.
The body of the stomach consists of majority of
secreting cells.

7. The Stomach
ANTRUM: The lower region of the stomach is called as
ANTRUM.
Grinds up swallowed food and regurgitates the
hydrochloric acid that is produced by the fundic and
body parietal cells.

8. Anatomy of Stomach
Stomach contain 5 types of Cells
Name of the Cell Function
Parietal Cell To Secrets HCL
G Cell To Secrets Gastrin
Chief Cell To Secrets Pepsin
Mast Cell To Secrets
Histamine
Mucus cell To Secrets Mucin

9. Acid Secretion
Acid secretion in the stomach is a continuous
process. Acid secretion is increased at the sight
or smell of food, at the meal times and during
stress.

10. Acid Secretion
There are 3 phases of acid secretion
1. Basal acid secretion: This secretion is devoid
of any stimulation and is governed by circadian
system of the body
2. Gastrin stimulated acid secretion: In this
phase, secretion is initiated by the presence of
food in stomach, sight, smell or even thought
of food.

11. Acid Secretion
3. Histamine stimulated acid secretion: Mast cells
secrete histamine. Stress and tensions
influence secretion of histamine. This secretion
is controlled by vagal stimulation.
 Vagal stimulation also releases acetylcholine.
These in turn stimulate histamine (H2) and
muscarinic receptors respectively present on
the parietal cells leading to increased gastric
acid secretion.

12. Formation of HCL

13. Role of HCL
 Strongly acidic fluid - Kills many microbes in food
 Stimulates the secretion of hormones that promote the flow of
bile and pancreatic juice.
 It is required for digestion of Proteins.
 Chemical breakdown of food.
 Create an environment for absorption of Nutrients, Vitamin
B12 and calcium.

14. Altered acid physiology & consequences
A mismatch between aggressive forces (mainly acid
and pepsin) and defensive forces (mucosal integrity) is
responsible for various acid related disorders. This
mismatch can occur because of
 Increased acid secretion, and/or
 Decreased mucosal defenses like-
1. Mucus
2. Mucosal blood flow
3. Bicarbonate
4. Cell renewal
5. Endogenous prostaglandins

15. Gastric Acid Pathogenesis
 Gastric acid plays a pivotal role in the pathogenesis of various acid
related disorders or acid-peptic disorders, including
 Reflux Esophagistis
 Non-erosive reflux disease
 Gastro Esophageal Reflux Disease
 Non-cardiac chest pain
 NSAID Induced gastritis
 Peptic Ulcers
 Functional Dyspepsia
 pathologic gastrointestinal hypersecretory conditions

16. Reflux Esophagistis
 Reflux esophagitis is better known as “heartburn.”
 It is often felt behind the breastbone as a burning
chest discomfort, feeling of food coming back into the
mouth as an acid or bitter taste.
 It mostly happens after meals and last a couple of
minutes to a couple of hours. It may not be relieved by
rest nor be caused by exercise, and may become worse
if you lie flat or bend over.

17. Symptoms
 Bad taste in the mouth
 Loss of tooth enamel
 Chronic sore throat
 Hoarseness
 Choking
 Cough or wheezing

18. Complications of Reflux Esophagistis
 If RE is not treated, the inflamed area may bleed
slowly. Too much blood loss may cause low blood
count.
 Damage to the lower esophagus may also cause scars to
form. Too much scarring causes the lower end of the
esophagus to narrow, making it harder and harder to
swallow.
 Some patients with severe scarring may have trouble
swallowing.

19. Complications of Reflux Esophagistis
 Barrett esophagus: sometimes called Barrett syndrome
or columnar epithelium lined lower oesophagus
(CELLO), refers to an abnormal change in the cells of the
lower portion of esophagus.
 When the normal squamous epithelium lining of the
esophagus is replaced by goblet cells (cells usually found
lower in the gastrointestinal tract), Barrett's esophagus is
diagnosed.
 A small number of people with Barrett’s esophagus
develop a rare but often deadly type of cancer of the
esophagus.

20. Gastro Esophageal Reflux Disease
 Gastro Esophageal Reflux Disease is the result of the
reflux of gastric contents into the esophagus such an
extent that it overcomes the mucosal defense and
causes injury to the esophageal mucosa

21. Factors causing reflux and contribution to GERD
 LES Related Disorder
1. A mechanical defect in LES
2. Inappropriate transient relaxation of LES
3. Hiatal hernia (also provides a reservoir for acid)
 Type of food
1. Fatty and/or spicy food eating habit
2. Coffee, citrus or tomato juices

22. Factors causing reflux and contribute to GERD
 Increased Gastric Pressure
1. Delayed gastric emptying
2. Obesity
3. Pregnancy
 Others
1. Certain medications
2. Smoking
Sometimes if pylorus is impaired, bile and other
duodenal contents reflux from duodenum to
stomach and to esophagus adding aggravation
GERD.

23. GERD Symptoms
Intermittent substernal burning of pain (heartburn) is
characteristic of GERD. Other symptoms include
1. Angina-like chest pain
2. Laryngitis
3. Hoarseness
4. Chronic cough
5. Bronchitis
6. Aspiration pneumonia

24. Non-erosive reflux disease
 NERD is defined as the presence of classic GERD
symptoms in the absence of esophageal mucosal
injury.

25. Symptoms
 persistent heartburn
 acid regurgitation
 Nausea
 Hoarseness in the morning or trouble swallowing
 May feel like food is stuck in the throat
 Bad breath
 Persistent dry cough
but they do not have visible esophageal injury.

26. Non-cardiac chest pain
 When acid from the stomach flows up into the
esophagus, it can cause a burning sensation in the
chest that's often mistaken for angina or a heart attack
 Because the pain is similar to heart pain (called
angina), patients present to emergency rooms
concerned about a heart attack and commonly
undergo cardiac tests). After these cardiac tests fail to
show evidence of heart disease, the patients receive
the diagnosis of NCCP.

27. Symptoms
 Non-cardiac chest pain typically is felt behind the
breast bone (sternum) and is described as
oppressive, squeezing or pressure-like. It may radiate
to the neck, left arm or the back (the spine). It may be
precipitated by food intake.
 Heartburn
 Fluid regurgitation
 Bitter or sour taste

28. Functional Dyspepsia
 Functional Dyspepsia defined as discomfort or pain in
the upper part of the abdomen.

29. Symptoms
 postprandial fullness and bloating
 Epigastric pain
 Early satiety
 Nausea
 Belching

30. Peptic Ulcer
 The two major risk factors known to impair
mucosal defenses and lead to peptic ulcers are
bacterium Helicobacter pylori (H. pylori) and the
frequent use of NSAIDs.
 Gastric acid, further, contributes to formation of
ulcers once mucosal defenses are impaired. But
acid usually does not cause ulcers independently.

31. Helicobacter pylori
 The risk of PUD is up to seven times higher in
patients with H. pylori infection than in general
population.
 More than 70% of patients with gastric ulcers and
more than 90% of patients with duodenal ulcers are
infected with H. pylori.
 H. pylori is thought to damage the gastric mucosa.

32. Symptoms of PU
 Main symptom is dull aching or gnawing epigastric pain or
burning 1 to 3 hours after eating as per the location of
ulcer.
 It is often relieved by eating or by antacids. Pain may
worsen in night because of increased acid secretion and
lack of food material in stomach to dilute the acid.
 The nighttime paid normally interferes with sleep. Nausea,
vomiting and bloating are the other symptoms.

33. Complications of PU
 Bleeding ulcers
 Perforation into the peritoneal cavity
 Penetration into adjacent organs
 Gastric/intestinal passage obstruction

34. NSAIDs Induced gastritis
Non Steroidal Anti-inflammatory Drugs NSAIDs
damage the GI mucosa by dual mechanism.
1. They cause direct irritation to GI mucosa.
2. They inhibit prostaglandin synthesis leading to
reduced mucosal integrity & mucosal defense.
The acid then contributes to formation of ulcers. Use
of NSAIDs increases the risk of PUD upto 20 fold.

35. pathologic gastrointestinal hypersecretory
conditions
 Gastric acid secretion is largely control by
cholinergic, histaminergic and
peptidinergic(especially gastrin) pathways. Disorders
in a number of these pathways can lead to gastric acid
hypersecretion.
Classification of gastric acid hypersecretory state
 associated with hypergastrinemia
 associated with hyperhistaminemia
 unknown etiology

36. Zollinger-Ellison Syndrome
 ZES is a clinical syndrome characterized primarily by
refractory peptic ulcer disease which is due to ectopic
release of gastrin by gastrinoma resulting in gastric
acid hypersecretion.
 Complications of Zollinger-Ellison Syndrome
 A person who has Zollinger-Ellison syndrome may
have only one gastrinoma or may have several
 In some ZES patient gastrinomas may be malignant
(cancerous)

37. Symptoms
 Burning pain in the abdomen
 Nausea
 Diarrhea
 Vomiting
 Bleeding from the stomach
 Weakness
 Fatigue

38. Pharmacotherapy for Acid Suppression
Different medications are available to inhibit the acids.
 ANTACIDS
 Histamine H2-Receptor Antagonists
 Proton Pump Inhibitors

39. Limitation of Antacids
 Antacids relieve the symptoms but cannot healing in
recommended dosage
 Have short duration of action (about 2 hours) and need frequent
dosing
 Antacids are ineffective for eradication H. pylori
 Rebound acid secretion phenomenon may be problematic
 Adverse effects (constipation with aluminum salts and diarrhea
with magnesium salts)
 Drug interactions
 Hampered absorption of other drugs because of change in pH

40. Limitations of H2-Receptor Antagonists
 Controls mainly histamine related acid secretions and has
very low efficacy in gastrin related secretions
 Recurrence rate is high in patients with H. pylori infection
 Healing is delayed in smokers and recurrence rate is high
 May interact with other medications
 Though generally well tolerated, H2-Receptor
Antagonists can cause headache and other side4 effects
like confusion, diarrhea & gynecomastia (with
cimetidine).

41. Proton Pump Inhibitors
 Proton Pump inhibitors were introduced in late 1980s.
 Proton Pump inhibitors bind to the Proton Pump on
parietal cell and inhibit the acid secretion regardless of
whether it is stimulated by histamine, acetylcholine or
gastrin.
 Proton Pump Inhibitors also have in vitro antimicrobial
activity against H. pylori though they cannot eradicate
H. pylori when used alone.

42. P.P.I. -
1. OMEPRAZOLE……1988
2. LANSOPRAZOLE…1991
3. PANTOPRAZOLE …1994
4. RABEPRAZOLE…..1999
Are all PPI’s the same..????

43. Comparison of all PPI
 All PPIs are effective in healing and maintenance of
ARD but they differ in their ability to control
symptoms rapidly and consistently
 Rabeprazole is different from other PPI because of
more rapid rate of activation, Rabeprazole results in a
faster onset of action and faster symptoms control
than other PPIs

44. Comparison of all PPI
Pharmacokinetic Profiles
Pharmacodynamic
Parameter
Lansoprazole Omeprazole Rabeprazole
At a pH of 1.2 2 2.8 1.3
At a pH of 5.1 90 84 7.2
At 10min 66% 47% 100%
At 45 Min 100% 83% 100%
Activation Time(min)
% Inhibition of the H+/K+-ATPase

45. Comparison of all PPI
 Food does not affect degree of absorption
 Rabeprazole, involving both cytochrome P450
mediated reaction in the liver and nonenzymatic
reactions, appears to confer an advantage over other
PPIs

46. Rabe.. 20
Indications:
 Reflux Esophagistis
 Non-erosive reflux disease
 Non-cardiac chest pain
 NSAID Induced gastritis
 Peptic Ulcers
 Functional Dyspepsia

47. Rabe… 20
Dosage and Administration
 20 OD for 4 to 8 weeks
 And in complicated ARD up to 40 mg for 4 to 8 weeks

48. Rabe…20
USPs
 The latest and potent PPI
 Maximum speed of onset of action
 Maximum acid control
 Maximum gastroprotection
 Greater and faster symptom relief
 Safe and convenient