3. Oesophagus
25cm long muscular tube
From pharynx to stomach
Behind trachea and in front of vertebral column
Solid food reaches stomach in 7 to 8 seconds
Liquids reaches stomach in 2 to 3 seconds
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
4. Stomach
Dilated part of Digestive system
Upper opening connected to Oesophagus
Lower opening connected to Duodenum
Both remain closed during gastric digestion
J shaped in standing position
Elastic muscular bag with capacity of 2 liters
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
5. Functions of the Stomach
Storage of food for 3 hours
Partial digestion of proteins and fats
Semi digested food from stomach enters the
Duodenum
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
6. Small Intestine
6 to 7 meter long, 2.5cm diameter
Lies in center of abdomen
Divided into 3 parts
1. First part – Duodenum
2. Second part – Jejunum
3. Third part – ileum
Alkaline Secretions
– Protects from acid contents of stomach
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
7. Large Intestine
• Large intestine
– 1.5meter long, 5 to 6cm diameter
– Divided into 3 parts
• Right ascending colon
• Transverse colon
• Left descending colon
• Sigmoid Colon & Rectum
– Temporary storage of faeces
– Anus is guarded by external & internal sphincters
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
14. • About 2 to 3 liters of gastric juice are secreted daily by special
secretory glands in the mucosa.
Water, mineral salts: secreted by gastric glands
Mucus: secreted by goblet cells in the glands and in the
stomach surface
HCl and Intrinsic factor: secreted by parietal cells in the
gastric glands
Inactive enzyme precursors: pepsinogens secreted by chief cell
in the gland.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
15. ACID Secretion
• There are 4 phases in the secretion of gastric acid:
1. The basal phase:
2. The cephalic phase:
3. The gastric phase:
4. The intestinal phase:
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
16. • The basal phase: A small amount of acid is always being secreted
into the stomach.
• The cephalic phase: 30% of the total HCLsecretions to be produced
is stimulated by anticipation of eating and the smell or taste of food.
This signalling occurs from the brain through the Vagus Nerve. It
activates parietal cells to release acid and ECL cells to
release histamine. The Vagus nerve also releases Gastrin Releasing
Peptide onto G cells.. Enterochromaffin-like cell
• The gastric phase: About 50% of the total acid for a meal is secreted
in this phase. Acid secretion is stimulated by distension of the
stomach and by amino acids present in the food.
• The intestinal phase: The remaining 10% of acid is secreted
when chyme enters the small intestine, and is stimulated by small
intestine distension and by amino acids.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
17. Mechanism of Acid Secretion in Stomach
Synthesized by the parietal cells of gastric mucosa and secreted into large
cannaliculi which are the deep invaginations of the plasma membrane of
the parietal cell.
The key player in acid secretion is H+/K+ ATPase or “PROTON PUMP"
located in the cannalicular membrane.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
18. • GI secretion is regulated by nerves (acetylcholine), hormones
(Gastrin) & pancrin substances (Histamine)
• These three factors results
1. Activation of ATPase at H+K+ pump in the parietal Cell.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
19. Inside the parietal calls
Water molecules dissociates and combine with CO2
Hydrogen ions and bicarbonate ions are formed
Carbonic anhydrase
Hydrogen ions thus formed comes out into the lumen by
the help of H+K+ATPase enzyme with exchange with Potassium
Releasing HCl in the gastric lumen upon stimulation
of acetylcholine, gastrin, and histamine
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
20. In parietal cells CO2 + H20 H2CO3 which further
dissociate into H+ and HCO3
-.
HCO3
- is transported to blood in exchange of Cl-. CL-
ions are transported into the lumen of the canaliculus.
H+ is pumped out of the cells into the lumen in
exchange of K+ through the action of proton pump
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
22. After taking food
Stimulation of Parasympathetic (vagal) take place
Release of acetylcholine
Direct Effect
Binds with Muscarinic
Receptor on the partial cell
Stimulates
Histaminocytes
to release
Histamine
Stimulates gastric
antrum to secrete
Gastrin
Release of HCl from H+K+ATPase
Parietal cells bear receptors for 3 stimulators of acid secretion:
Acetylcholine (muscarinic type receptor)
Gastrin
Histamine (H2 type receptor)
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
23. ACID PEPTIC DISORDERS
• Acid peptic disorders include a number of conditions
whose pathophysiology is believed to be the result of
damage from acid and peptic activity in gastric
secretions
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
25. DRUGS FOR PEPTIC ULCER
Peptic ulcer occurs in that part of the gastrointestinal tract (g.i.t)
which is exposed to gastric acid and pepsin i.e. the stomach and
the duodenum.
The etiology of peptic ulcer is not clearly known. It results
probably due to an imbalance between the aggressive (acid,
pepsin and H. pylori) and the defensive (gastric mucosa and
bicarbonate secretion, prostaglandins, innate resistance of the
mucosal cells) factors
26. Approaches for the treatment of peptic ulcer are
1.Reduction of gastric acid secretion
a. H2 antihistaminics :Cimetidine,Ranitidine,Famotidine, Roxatidine
b. Proton pump inhibitor : Omeprazole, Lansoprazole,Pantoprazole
c. Anticholinergics :Pirenzipine, Propanatheline,Oxyphenonium,Doxepin,
d. Prostaglandin analogues : Misoprostal, Enprostil,Rioprostil
32. Pantoprazole
Inhibits the final common step in gastric acid secretion.
These accumulates in the acidic environment of the parietal cells after
absorption .
There it is converted to a cyclic sulphenamide which react covalently with
the SH groups of the H+K+ATPase enzyme and inactivate it irreversibly.
Acid secretion resumes only when new H+K+ATPase molecules are
synthesized.
Pantoprazole exerts its full effect in a strongly acidic environment (pH< 3)
and remains mostly inactive at higher pH values, which explains its
selectivity for the acid secreting parietal cells of the stomach.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
33. • Pantoprazole are substituted benzimidazole derivatives, weak
bases,
which accumulate in the acidic space of the parietal cell before
being converted in the canaliculi (small canal) of the gastric
parietal cell,
an acidic environment, to active sulfenamide derivatives.
• This active form then makes disulfide bonds with important
cysteines on the gastric acid pump, inhibiting its function
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
34. Indications
Duodenal ulcer
Gastric ulcer
Reflux oesophagitis, GERD
Zollinger Ellision Syndrome (ZES).
Duodenal ulcer associated with Helicobacter pylori
infection as a part of combination therapy
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
36. MOA Of Domperidone
D2 blocker in CTZ and GI Tract.
D2 blocker in upper GIT:- Resulting Prokinetic efffect
Increase LES tone and increase peristalsis along with
stomach contraction
Decrease intestine transit time
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
37. Domperidone
• Peripherally selective dopamine D2 receptor antagonist that
was developed by Janssen Pharmaceutical(Motilium) and is
used as
1. an antiemetic
2. Gastroprokinetic agent.
Through its effects on the chemoreceptor trigger zone and
motor function of the stomach and small intestine
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
39. June, 2018
Domperidone is not currently a legally marketed drug or
approved for sale in the U.S.
FDA currently allows patients 12 years of age and older
with various gastrointestinal (GI) conditions to be treated
with domperidone through the Expanded Access to
Investigational Drugs program.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
40. Rationale of Combination:
Both Pantoprazole and domperidone are different and
complimentary to each other.
Upper gastrointestinal disorders are frequently
associated with a combination of hyperacidity and
dysmotility.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
41. Dysmotility
• As a result, acidic chyme may either stagnate in
stomach and duodenum or may be evacuated by
reverse peristalsis (vomiting or nausea).
• Reflux of acid contents of stomach cause erosions of
lower part of oesophagus which may further aggravate
nausea and vomiting.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
42. • Since both hyperacidity and dysmotility are present at
the same time in disorders like gastroesophageal reflux
disease (GERD) and nonulcer dyspepsia (NUD),
• a combination of drugs which will take care of both
would be ideal.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
43. Rational
• Pantoprazole is a potent gastric acid inhibitor that blocks the
final stage of acid secretion.
• Hence, whatever may be the stimulus, hyperacidity will be
controlled by pantoprazole.
• In contrast, domperidone increases gastrointestinal motility,
thereby facilitating the movement of acid contents further
down in the intestine preventing reflux esophagitis and
thereby controlling nausea and vomiting.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
44. Indications
Management of GERD; gastritis,
NUD,
Gastric or duodenal ulcer,
Dyspepsia,
Bloating, fullness,
Nonsteroidal anti-inflammatory drug (NSAID)-induced
dyspepsia
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
47. • hiatus hernia is when part of your stomach moves up into
your chest
• Gastroparesis is a long-term (chronic) condition where the
stomach cannot empty in the normal way
• Coeliac disease is a condition where our immu
• ne system attacks your own tissues when we eat gluten.
This damages our gut (small intestine) so we are unable to
take in nutrients.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
49. • In normal digestion, the lower esophageal sphincter
(LES) opens to allow food to pass into the stomach and
closes to prevent food and acidic stomach juices from
flowing back into the esophagus.
• Gastroesophageal reflux occurs when the LES is weak
or relaxes inappropriately, allowing the stomach’s
contents to flow up into the esophagus
• Peristalsis movement
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
50. Dose
Adults and adolescents over 12 years of age and
weighing ≥35kg,
the recommended maximum dose in 24 hours is 30mg
Dose interval:
10mg up to three times daily).
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
51. S/E especially in high dose over
• Serious effects on the heart with domperidone, including
prolongation of the QT interval (an alteration of the electrical
activity of the heart) and arrhythmias (unstable heartbeats)
• Domperidone may be associated with an increased risk of QT
interval prolongation, serious ventricular arrhythmia or sudden
cardiac death. The risk of serious cardiac events appears to be
highest in patients over the age of 60 years, and is increased
with higher doses and prolonged treatments.
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
52. A higher risk was observed in:
• Those over the age of 60 years
• People taking daily oral domperidone doses of more than 30mg
• Those taking QT-prolonging medicines (Chlorpromazine.
Haloperidol.
Droperidol.
Quetiapine.
Olanzapine.
• Amisulpride0
• or CYP3A4
inhibitors(clarithromycin, erythromycin, diltiazem, itraconazole,
ketoconazole)
1/25/2024
Pabitra Thapa,Sr. Product manager, Asian
Pharmaceuticals
eclare confined to a single region of the gut, the gastric fundus, where they form the major endocrine cell population.
The primary function of gastric chief cells is the synthesis and release of the proenzyme pepsinogen, which subsequently, in an acid environment, is converted to the acid protease pepsin.
your belly feels full and tight, often due to gas.- Bloating.
