The document discusses the physiology of acid secretion in the gastrointestinal tract and the pathophysiology of peptic ulcers. It covers the anatomy of the stomach and types of cells that secrete acid and other substances. Risk factors for peptic ulcers include H. pylori infection and NSAID use. Diagnosis involves endoscopy, urea breath test, and stool antigen test. Treatment includes lifestyle modifications, antacids, H2 receptor antagonists, proton pump inhibitors, and anticholinergics. Surgery may be required in some cases.

1. Presented by: Zeel Mevada
M.Pharm sem 2
(192280825005)

2. Content:
introduction
Physiology of acid secretion
related Disorders
Risk factor
Pathophysiology
Diagnosis
treatment

3. The gastrointestinal tract
(GIT, alimentary tract, gut)
 It consists of an irregular
tube about 6 m long,
extending from the mouth to
the anus.
 The upper GIT Which
includes the mouth,
oesophagus and stomach.
 The lower GIT Which
comprises the duodenum,
jejunum, ileum, colon,
rectum and anus.
 The accessory organs liver,
gallbladder and pancreas

4. GASTRIC ANATOMY:
Gastric glands have several types of secreting cells
Goblet cells Mucus
Surface mucous cells Mucus
Parietal cells Hydrochloric acid
Chief cells pepsinogen , an inactive form of the
protein– digesting enzyme pepsin.
Enteroendocrine cells Serotonin and histamine as autocrine
regulators
G-cells Gastrin hormone
In addition to these products, the gastric mucosa (probably the parietal
cells) secretes a polypeptide called intrinsic factor, which is required for
absorption of vitamin B12 in the small intestine.

6. Secretion of HCL
F

7. Physiology of acid secretion

8.  Dysphagia:
 Difficulty swallowing, caused by obstruction of the esophagus
 Obstruction may be caused by
tumors, congenital narrowing
Neurologic disorders such as brain injury stroke or Parkinson’s
disease may affect voluntary swallowing or peristalsis of the
esophagus
 Dyspepsia
Epigastric fullness, discomfort, indigestion
 Odynophagia
Painful swallowing usually associated with dysphagia
 Heartburn
Burning sensation retrosternally associated with reflux
Abnormalities of the GIT

9.  Anorexia
Loss of appetite
 Haematemesis
Vomiting blood (could be red or altered “coffee ground”)
 Melaena
Passing of black tarry, offensive stool (usually due to upper
GI bleeding)
 Haematochezia
Passing blood through rectum (PR bleeding)
 Gastritis
Inflammation of the gastric mucosa
Acute gastritis
Chronic gastritis
Abnormalities of the GIT

10. Types of ulcers:
Typesof ulcers
Duodenal ulcers
Gastric ulcer
Stress ulcer
Zolinger-elison syndrom
Drug associated ulcer
Reflux
esophagitis

11.  A localized loss of gastric as well as duodenal mucosa
leads to the formation of peptic ulcer.
A peptic ulcer is a sore on the lining of your stomach,
small intestine or esophagus. A peptic ulcer in the
stomach is called a gastric ulcer. A duodenal ulcer is a
peptic ulcer that develops in the first part of the small
intestine (duodenum). An esophageal ulcer occurs in
the lower part of your esophagus.

12.  Peptic ulcer arises when the normal mucosal defense
mechanisms (mucus blood flow formation of HCO3-
PGE2 ) are impaired or overpowered by damaging
factors (acids pepsin pylori)
 Ulcers occur 5 times more commonly in the dudenum
and 95% of them are found in pyloric channel

14. Classification of peptic ulcer
 Peptic ulcers classified based on region or location of illness
– Stomach (called gastric ulcer)
– Duodenum (called duodenal ulcer)
– Esophagus (called Esophageal ulcer)
– Meckel's Diverticulum (called Meckel's Diverticulum ulcer)
Modified Johnson classification of peptic ulcers
Type I: Ulcer along the lesser curve of stomach
Type II: Two ulcers present - one gastric, one duodenal/prepyloric
Type III: Prepyloric ulcer
Type IV: Proximal gastroesophageal ulcer
Type V: Anywhere (associated with chronic NSAID use)

20. • NSAIDs can cause damage to the gastro duodenal mucosa via
several mechanisms, including the topical irritant effect of these
drugs on the epithelium, impairment of the barrier properties of the
mucosa, suppression of gastric prostaglandin synthesis, reduction of
gastric mucosal blood flow and interference with the repair of
superficial injury. The presence of acid in the lumen of the stomach
also contributes to the pathogenesis of NSAID-induced ulcers and
bleeding, by impairing the restitution process, interfering with
haemostasis and inactivating several growth factors that are
important in mucosal defence and repair.

21. inflammation
-- causes chronic and
by
• H. pylori
indolent
damaging the mucosal defense
system by reducing the thickness
of the mucus gel layer, diminishing
mucosal
interacting
blood
with
flow,
the
and
gastric
epithelium throughout all stages
of the infection.
• H. pylori infection can also
increase gastric acid secretion by
various antigens,
factors, and soluble
producing
virulence
mediators
Helicobacter pylori & Ulcer

22. Helicobacter pylori &
Ulcer

23. • Tumors of the gastrin-
secreting endocrine cells of
the pancreas or, less
frequently, the duodenal
wall.
• Leads to excessive acid
production by the G.I. tract.
• Development of serious and
aggressive peptic ulcers.
• Complications can include perforation, hemorrhage and
obstruction.
• Treatment may include resection of tumor, administration of
H2 receptor antagonists, anticholinergics andantacids.

24.  Gastrointestinal bleeding. (Sudden large
bleeding can be life threatening)
 Cancer (Helicobacter pylori as the etiological factor
making it 3-6 times
 likely to develop stomach cancer)
 Perforation (hole in the wall)
 Penetration.
Complications of peptic ulcer

25. Endoscopy:
Flexible tube
fitted with
camera is
threaded down
the esophagus
in to stomach
to see the ulcer
by physician

26. • Barium meal:
Barium liquid is drunk making ulcer
visible on X- ray

27. Test for diagnosing H.pylori

28.  invasive techniques (endoscopy with biopsies for histology,
culture and a rapid urease test) and
 non-invasive techniques (e.g. serology, the13C-urea breath test
and the stool antigen test).
 urea breath test and the stool antigen test, detect active
infection: these are called ‘active tests’
 Non-invasive tests (e.g. serology, urine, near-patient tests) are
markers of exposure to H. pylori but do not indicate if active
infection is ongoing; these are ‘passive tests’.

29. Rapid urease test
 This gastric biopsy test is based on the activity of the H. pylori
urease enzyme, which splits the urea test reagent to form
ammonia.
 Ammonia increases pH, which is detected by the indicator
phenol red. Although some of the commensal flora of the
oropharynx produce urease, which is swallowed in the saliva,
this weaker enzyme is denatured rapidly in the acid lumen of
the stomach (pH < 2.0).
 The tests give a result in 1 h to 24 h, depending in part on the
format of the test and the number of Helicobacter in the biopsy
specimen.

30. Non-invasive test (passive test)
• Serology
 the most common is the enzyme-linked immunosorbent
assay (ELISA) test, which detects the totality of the
immunoglobulin in a patients’ serum and can detect any of
the immunoglobulin isotypes.
 If the antibody response to specific antigens is important, the
separate ELISA test has to be done.
 most important disadvantage of serological tests is that they
do not distinguish between active infection and a previous
exposure to H. pylori. Antibody levels can persist in the blood
of individuals cured of H. pylori infection for long periods of
time.

31. CagA and vacA antibodies
 CagA is a 120-kDa protein of H. pylori with high
immunogenicity. Its gene (cagA) is contained in the
pathogenicity island (PAI) of the chromosome of H. pylori.
 Individuals infected with cagA-positive strains of H. pylori
tend to have more severe gastritis, a higher likelihood of
developing gastric atrophy and intestinal metaplasia, and a
higher incidence of duodenal ulcer and intestinal-type gastric
cancer.12
 The vacuolating toxin (vacA) is an 87-kDa protein and its
gene is not located in the pathogenicity island. However, it is
secreted by Helicobacter strains that contain the PAI. The
vacuolating toxin (vacA) is activated at low pH, is resistant
to acid and pepsin.

32. Active tests for the detection H. pylori
These tests are useful for the initial detection of H. pylori and for confirming eradication.
 During the test you will swallow a capsule containing
urea, which is made from an isotope of carbon. (Isotopes
of carbon occur in minuscule amounts in nature, and can
be measured with special testing machines.)
 If H. pylori is present in the stomach, the urea is broken
up and turned into carbon dioxide.
 The carbon dioxide is absorbed across the lining of the
stomach and into the blood.
 It then travels in the blood to the lungs where it is
excreted in the breath. Samples of exhaled breath are
collected, and the isotopic carbon in the exhaled carbon
dioxide is measured.
 if the urea breath test is positive and the isotope is
detected in the breath, it means that H. pylori is present in
the stomach. If the isotope is not found in the breath, the
test results are negative for the infection.

33.  Stool is placed in a diluent vial and then a drop of the liquid is
placed in the well of the test. Early results are promising, with
sensitivity and a specificity of 92%.66 This test might be
useful as
 a near-patient test in primary care settings. It also has a
particular advantage in needle- phobics and children, who are
generally averse to venepuncture.
 In principle, the test can be amended to pick-out specific
proteins, such as cagA or vacA, which could be used to
determine the virulence type of the infecting strain.
Stool antigen test

36. Life style modification
Drug treatment
Surgery

37. Life style modification
 Diet
 Large amounts of food should be avoided because
stretching or swelling of stomach  painful symptoms.
 Take Fruits and Vegetables. Stop Coffee and Carbonated
Beverages, Spices and Peppers .
 Exercise
 Addiction: Stop alcohol and stop smoking
 Stress Relief
 Stress relief programs have not been shown to promote
ulcer healing, but they may have other health benefits.

38. Goals of therapy:
i. Promotion of ulcer healing
ii. Prevention of complication
iii. Prevention of relapse

39. antacid
 These are basic substances which neutralize gastric acid and
raise pH of gastric contents.
 In view of safety and efficacy of the morden drugs, antacids are
now prescribed less frequently for these disorder(often used as
nonprescription remedies)
 The potency of an antacid is generally expressed in terms of its
acid neutralizing capacity(ANC)
 Antacid are usually divided into two classes: systemic an non-
systemic antacids

40. Systemic antacids
Sodium bicarbonate: acts rapidly has a brief duration
of action and raises the ph of gastric secretions to about
7.4.
Production co2 and in stomach leads to distention,
discomfort.
Increase sodium load leads to worsen in CHF with
edema.
Large dose produces alkalosis.

41. Non systemic antacid
 Poorly absorbed from GI tract and do not disturb systemic
acid-base balance
 Classified as buffer type & non buffer type

42.  Al(OH)2: cause constipation
 Formation of aluminum phosphate
 Smooth muscle relaxation
 Prevent absorption of phosphate so they lead to
hypophosphataemia so use for hyperphosphatemina and
phosphate stone
 Magnesium trisilicate: formation of sio2 during neutralization
reaction forms a gelatinous coating that prolongs action of
antacid
 MGCL2and MGCO3 production cause diarrhoea as a side
effect
 note : These two agent are , therefore commonly administered
together.

43. Non buffer type -antacid
 Calcium carbonate
 Magnesium hydroxide

44.  Caco3 : may cause bleaching due to liberate co2.
 Excessive dose of caco3 if given along with milk can
lead to hypercalcaemia, renal insufficiency and
metabolic alkalosis.
 (called milk alkali syndromes).
 Caco3 that cause constipation due to formation of
calcium stearate
 MGCO3 that cause diarrhea.
 It usually given with aluminum hydroxide.

45. Drug interaction
1. Antacid , usually not given within 2 hrs of
administration of tetracycline, fluroquinolones,
digoxin or iron salt.
2. Antacid decrease absorption of acidic drug like
barbiturate, phenytoin, and NASAIDs.

46. H2 RECEPTOR ANTAGONISTS
 Cimetidine, Ranitidine, Famotidine, Nizatidine
MECHANISM OF ACTION:
H2 receptor antagonist inhibits acid production by
reversibly competing with histamine for binding to
H2 receptors on basolateral membrane of parietal
cells.
Also they cause suppression of stimulated (feeding,
gastrin, hypoglycemia, or vagal stimulation) acid
production.

47. THEREPEUTIC USES:
1. DU and GU.
2. ZES.
3. GERD (Gastro esophageal reflux disease).
4. As prophylactic in stress ulcers.

49.  Adverse effect
 These are safe drug-headache , fatigue, myalgia and
constipation may occur but rarely
 Cross placental barrier and are also secreted in breast
milk(should be avoided in pregnancy)
 Interaction:
 Inhibits CYP-450 leads to inhibits the metabolism of many
drugs so that they accumulate to toxic level.
 Contraindication:
 Renal impairment
 Hepatic failure

50. Proton pump inhibitor
Disrupt chemical binding in stomach cells to reduce acid production,
lessening irritation and allowing peptic ulcers to heal.
MOA:
Most effective drugs in anti ulcer therapy
Block the last step in the secretion of gastric acid in combining with
hydrogen, potassium, and adenosine triphosphate in the parietal cell of
the stomach.
Irreversible inhibitor of H+/k+ ATPase to apical membrane oh the
parietal cell.
React covalently with –SH group of H+/K+
ATPase enzyme.
Activation in canaliculi and bind covalently to extracellular domain of
ATPase.

52. • Adverse effect:
• Hepatic dysfunction
• Dizziness
• Nausea
• Headches
• Interaction:
• Inhibits oxidation of certain drugs: diazepam,
phenytoin, warfarin.

53. anticholinergic
 Anti muscarinic drug s were mainly used for peptic ulcer
 Theses drug block basal secretion more effectively also increase gastric empting time .
 Quaternary anti muscarinic drug like peopantheline and oxyphenonium more preferred
because they do not cross BBB.
 M1 receptor blocker such as pirenzepine and telenzepine are being use for ulcer
 These drug block m1 receptor at paracaine cell in gastric mucosa.
 These drug heal ulcer as well as prevent recurrences of duodenal ulcer
 Side effect:
 dry mouth ,
 blurred vision
 Constipation
 Urinary retention

54. Ulcer protactive agents
 Sucralfate: consists of the octasulfate of sucrose to which
AL(OH3) has been added.
 in an acidic environment pH<4, agent undergoes extensive
cross linking to production a viscous , sticky polymers that
adheres to epithelial cells and ulcer creates for up to 6 hours
after single dose administration.
 There is some evidence to suggest that it also stimulator
mucosal PEG2synthesis and HCO3- secretion.
 Also believed to bind epithetilial as well as fibroblast growth
factor which promotes mucosal repair.
 It promote ulcer healing
 Sucrelate is administer in a dosage of 1 gm four time daily.

55. 55
• Other use:
1. stomatitis
2. Gel using for burn dressing and sores.
3. High dose prevent phosphate stone in kidney
4. Surface local anesthetic also available
5. It bind to phosphate ion in intestine, hypophosphataemia may
occur
6. sucralfate adsorbs tetracycline fluroquinolones, phenytoin and
digoxin
7. Colloidal bismuth subcitrate & bismuth subsalicylate
8. Form an acid resistant protective coating over ulcer base
9. The surface of gastric mucosa and has direct antimicrobial
activity against this ulcer causative organism.
10. Dosage of 120 mg orally four time a day.

56. Carbenoxolone sodium:
Its use outdated because of the adverse effect
(minralocorticoides like side effect such as hypotension
Na+ and water retention and hypokaleamia)
56

57. Antibiotics for h.pylori
Clarithromycin 500mg
Amoxicillin1 G
Metronidazole 500 mg
Tetracycline 500 mg
Levofloxacin 500 mg
Rifabutin 300 mg

60. Surgical procedures
• Major Abdominal Surgery
• Vagotomy:-cuts the vagus nerve and interrupts
messages from the brain that stimulate acid
secretion in the stomach. This surgery may impair
stomach emptying; a recent variation that cuts
only parts of the nerve may reduce this
complication.
• Antrectomy:- removes the lower part of the
stomach, which manufactures the hormone
responsible for stimulation of digestive juices.

61. • Pyloroplasty:- enlarges the opening into the
small intestine so that stomach contents can
pass into it more easily.
• Total gastrectomy:-Removing the entire
stomach is done only for resistant Zollinger-
Ellison syndrome or extensive cancers.

62. gastrectomy

64. Reference:
o Principle of pharmacology by HL SHARMA ,KK SHARMA by
paras medical publisher .Pg no 390 -401
o Essential of medical pharmacology by KD Tripathi ,jaypee
publication,6th edition Pg no 627-638
o Harsh Mohan, text book of pathology, the respiratory system, 6th
edition, page-461-464.
o Principle of anatomy and physiology by Gerald Tortota, Bryan
Derrickson by Wiley publicsher,14th edition.Pg no 930-932
o Ricci C, Holton J, Vaira D. Diagnosis of Helicobacter pylori:
invasive and non-invasive tests. Best Practice & Research Clinical
Gastroenterology. 2007 Apr 1;21(2):299-313.