Peptic ulcer disease types, clinical features, investigations and treatment

1. Dr.M.Krishna Vasudev
Dept of General Medicine
Peptic Ulcer Disease

2. Peptic Ulcer Disease
 Condition characterized by
 Erosion of GI mucosa resulting from digestive
action of HCl and pepsin

3. Peptic Ulcer Disease
 Ulcer development
 Lower esophagus
 Stomach
 Duodenum
 10% of men, 4% of women

4. Types
 Acute
 Superficial erosion
 Minimal erosion
 Chronic
 Muscular wall erosion with formation of fibrous
tissue
 Present continuously for many months or
intermittently

6. Peptic Ulcers:
Gastric & Dudodenal

7. Classification
₪ Stomach (called gastric ulcer)
₪ Duodenum (called duodenal ulcer)
₪ Oesophagus (called Oesophageal ulcer)
Types of Gastric ulcer(Modified johnson criteria):
₪ Type I: Ulcer along the lesser curve of stomach
₪ Type II: Two ulcers present - one gastric, one
duodenal
₪ Type III: Prepyloric ulcer
₪ Type IV: Proximal gastroesophageal ulcer
₪ Type V: Anywhere(NSAID induced)

8. Gastric Ulcers
 Commonly found on lesser curvature in close
proximity to antral junction
 Less common than duodenal ulcers
 Prevalent in women, older adults, persons from
lower socioeconomic class

9. Gastric Ulcers
 Characterized by
 A normal to low secretion of gastric acid
 Back diffusion of acid is greater (chronic)

10. Gastric Ulcers
 Critical pathologic process is amount of acid able
to penetrate mucosal barrier
 H. pylori is present in 50% to 70%

11. Gastric Ulcers
 H. pylori is thought to be more destructive when
noxious agents are used, or patient smokes

12. Gastric Ulcers
 Drugs can cause acute gastric ulcers
 Aspirin, corticosteroids, NSAIDs, reserpine
 Or known causative factors
 Chronic alcohol abuse, chronic gastritis

13. Duodenal Ulcers
 Occur at any age and in anyone
 ↑ Between ages of 35 to 45 years
 Account for ~80% of all peptic ulcers

14. Duodenal Ulcers
 Associated with ↑ HCl acid secretion
 H. pylori is found in 90-95% of patients
 Direct relationship has not been found

15. Duodenal Ulcers
 Diseases with ↑ risk of duodenal ulcers
 COPD, cirrhosis of liver, chronic pancreatitis,
hyperparathyroidism, chronic renal failure
 Treatments used for these conditions may
promote ulcer development

16. Peptic Ulcer Disease
Clinical Manifestations
 Common to have no pain or other symptoms
 Gastric and duodenal mucosa not rich in sensory
pain fibers
 Duodenal ulcer pain
 Burning, cramplike
 Gastric ulcer pain
 Burning, gaseous

17. SYMPTOMS
An early sense of fullness with eating frequent burping or hiccupping
Stomach pain wakes you up at night low blood cell count (anemia)
Blood in the stools Vomiting
Melena Appetite changes
hematemesis (vomiting of blood) Unexplained weight loss
Water brash Nausea
Bloating Burning pain

18. DUODENAL ULCER
 Classic symptoms of a duodenal ulcer include burning,
gnawing, aching, or hunger-like pain, primarily in the
upper middle region of the abdomen below the
breastbone (the epigastric region).
 Pain may occur or worsen when the stomach is empty,
usually two to five hours after a meal. Symptoms may
occur at night between 11 PM and 2 AM, when acid
secretion tends to be greatest.
 Feel better when you eat or drink and then worse 1 or 2
hours later (duodenal ulcer)
GASTRIC ULCER
 Symptoms of a gastric ulcer typically include pain soon
after eating. Symptoms are sometimes not relieved by

19. Peptic Ulcer Disease
Complications
 3 major complications
 Hemorrhage
 Perforation
 Gastric outlet obstruction
 Initially treated conservatively
 May require surgery at any time during course of
therapy

20. Peptic Ulcer Disease
Diagnostic Studies
 Endoscopy procedure most often used
 Determines degree of ulcer healing after treatment
 Tissue specimens can be obtained to identify H.
pylori and to rule out gastric cancer

21. Peptic Ulcer Disease
Diagnostic Studies
 Tests for H. pylori
 Noninvasive tests
 Serum or whole blood antibody tests
 Immunoglobin G (IgG)
 Urea breath test
 Invasive tests
 Biopsy of stomach
 Rapid urease test

22. Peptic Ulcer Disease
Diagnostic Studies
 Barium contrast studies
 Widely used
 X-ray studies
 Ineffective in differentiating a peptic ulcer from a
malignant tumor

23. Peptic Ulcer Disease
Diagnostic Studies
 Gastric analysis
 Identifying a possible gastrinoma
 Determining degree of gastric hyperacidity
 Evaluating results of therapy

24. Peptic Ulcer Disease
Diagnostic Studies
 Laboratory analysis
 CBC
 Urinalysis
 Liver enzyme studies
 Serum amylase determination
 Stool examination

25. AIMS OF ULCER TREATMENT
 Promotion of ulcer healing.
 Symptomatic relief of pain.
 Prevention of recurrence (relapse).
 Prevention of complications

26. DRUG TREATMENT OF PEPTIC ULCER
I. Gastric hyposecretory drugs.
 H2 receptor blockers
 Muscarinic receptor blockers
 Proton pump inhibitors
II. Eradication of H. pylori infections
To prevent relapse

27. DRUG TREATMENT OF PEPTIC ULCER
III. Mucosal cytoprotective agents.
 Sucralfate
 Colloidal bismuth
 Prostaglandin analogues
IV. Neutralizing agents (antacids).

28. Gastric hyposecretory drugs
 H2 receptor blockers
 Muscarinic receptor blockers
 Proton pump inhibitors
 Decreasing gastric acidity can reduce absorption of
ketoconazole & iron preparation, digoxin.

29. Proton Pump Inhibitors
Mechanism of action
Irreversible inhibition of proton pump (H+/ K+ ATPase)
that is responsible for final step in gastric acid secretion
from the parietal cell.
PP inhibitors include:
 Omeprazole
 Lansoprazole
 Pantoprazole
 Esomeprazole

30. Illustration of Gastric secretion by parietal cells

31. Pharmacokinetics:
 They are prodrugs – taken orally.
 are given as enteric coated capsules
 They are rapidly absorbed from the intestine.
 They are activated in the acidic medium of the
secretory parietal cell canaliculus.
 They are inactivated if (combined with H2 receptor
blockers).

32.  Have long duration of action (> 12 h-24 h).
 Once daily dose is sufficient
 Bioavailability is reduced by food.
 Given 1 h before meal.
 Are metabolized in the liver by CytP450.
 They are more potent than H2 receptor blockers
 Inhibits basal and stimulated-acid secretion.
 Dose reduction is required in severe liver failure.

33. USES
1. Zollinger Ellison syndrome (First choice).
2. Resistant severe peptic ulcer ( 4-8 weeks).
3. Reflux esophagitis.
4. Eradication of H. pylori.

34. ADVERSE EFFECTS
 GIT disturbances: nausea, vomiting, diarrhea
 Achlorhydria.
 Hypergastrinaemia
 Gastric hyperplasia.
 Increased bacterial flora (nitrosamine)

35. H2 receptor blockers
Mechanism of action
 They competitively and reversibly block to H2 receptors
on the parietal cells thus reduce gastric secretion. They
include:
 Cimetidine
 Ranitidine
 Famotidine
 Nizatidine

36. Pharmacokinetics
 Good oral absorption
 Plasma half life (1-3 h).
 Duration (4-12 h).
 First pass metabolism (50% Except Nizatidine 100 %
bioavailability).
 Given before meals.
 Metabolized by liver.
 Excreted mainly in urine.
 Cross placenta & excreted in milk

38. Pharmacological actions:
 Inhibit histamine, gastrin, cholinergic drug -induced
secretions.
 Reduce basal and food-stimulated gastric secretion.
 Reduce pepsin activity.
 Promote mucosal healing & decrease pain

39. USES:
• Duodenal Ulcer (6-8 weeks).
• Benign gastric ulcer (8-12 weeks).
• Reflux esophagitis
• Zollinger Ellison Syndrome (large doses).
• Pre-anesthetic medication (To prevent
aspiration pneumonitis).
• Eradication of H. pylori infections.

40. Adverse Effects of H2 blockers:
1. GIT disturbances: nausea, vomiting
2. CNS effects:
Headache, dizziness, confusion (elderly – renal or
hepatic dysfunction).
3. CVS effects
Bradycardia and hypotension (rapid I.V.)

41. Cimetidine has other adverse effects:
4. Endocrine effects
 Antiandrogenic actions (gynecomasteia – impotence)
 Galactorrhea in women.
5. Cytochrome P450 inhibitor: decrease metabolism of
oral anticoagulant, phenytoin, benzodiazepines.

42. Precautions
1. Maintenance dose (Relapse may occur).
2. Dose reduction in severe renal or hepatic failure and
elderly.

43. ANTICHOLINERGIC DRUGS
1. Non selective muscarinic blockers:
Oxyphenonium, dicyclomine
 Decreased gastric motility
 Delayed gastric emptying
- Heart burn
- Atropine like side effects.

44. 2. Selective muscarinic blockers:
Pirenzepine - Telenzepine
 Blocks M1 receptors on the parietal cells.
 Selectively inhibit gastric acid secretion
 No effect on gastric motility
 Less side effects of cholinergic blockade.
 No effect on CNS.
 Dose : 50 mg bid for 4-6 weeks
Uses
1.Adjuvants to H2 receptor blockers.
2. decrease nocturnal pain in peptic ulcer.

45. Eradication Of H Pylori
 Is a bacteria that causes chronic inflammation of the
inner lining of the stomach.
 Produce enzymes (tissue damage), inflammation –
ulcer.
 Duodenal ulcer - Gastric ulcer
 Risk factor for esophagus and stomach cancers.
 Eradication is important to prevent recurrence
of ulcer.

46. Helicobacter pylori in association with gastric
mucosa

47. Treatment
 Combined therapy is usually used.
 Clarithromycin, tetracycline, amoxicillin
 Proton pump inhibitors or H2 receptor blockers.
 Bismuth compounds
 Metronidazole.
 Resistance may develop to antibiotics.
 Better eradication is obtained using proton pump
inhibitors & clarithromycin.

48. Treatment
The standard first-line therapy is "triple therapy" consisting
of proton pump inhibitors as omeprazole and the
antibiotics clarithromycin and amoxicillin.

49. REGIMEN DOSE DURATION
Bismuth
Metronidazole
Tetracycline
525 mg qid
250 mg tid
500 mg qid
2 weeks
omeprazole
Metronidazole
Clarithromycin
20 mg bid
500 mg bid
500 mg bid
1 week
omeprazole
Amoxacillin
Clarithromycin
20 mg bid
500 mg qid
500 mg bid
1 week
omeprazole
Bismuth
Metronidazole
Amoxacillin or / Tetracycline
20 mg bid
525 mg qid
500 mg qid
500 mg qid
week

50. Mucosal protective agents.
1. Sucralfate
2. Prostaglandin analogues.
3. Colloidal bismuth

51. Sucralfate
Sucrose octaphosphate + aluminium hydroxide
Mechanism of action
1. In acidic pH, sucralfate dissociates into its
components.
2. The negatively charged sucrose octaphosphate
binds with positively charged protein molecules
found in damaged mucosa (Coat over the ulcer).
3. Promote ulcer healing.
4. Inhibition of pepsin.

52. 3. Stimulation of mucosal protective mechanisms
(mucous and bicarbonates secretion).
Kinetics
 Orally, poor systemic absorption.
 Duration (6 h).
 Excreted in feces.
 Avoid co-administration of antacid or H2 blocker.
 Bette taken on empty stomach.

53. Therapeutic Uses
 Benign gastric and duodenal ulcer.
 Chronic gastritis.
Adverse effects
 Constipation and dry mouth.
 Interferes with absorption of some drugs tetracycline,
theophyline, Tricyclic antidepressant.

54. 2. Misoprostol
 Prostaglandin Analogues (PGE1 )
  HCL secretion.
 Promote tight junction of gastric cells prevent back
diffusion of HCL.
  mucous and bicarbonate secretion.
blood flow of mucosa improve healing of ulcer.
Kinetics
Orally, 30 min.
is converted into active metabolite.
Excreted in urine- must be taken 3-4 times/day.

55. Therapeutic uses
 Prevention of NSAIDS-induced peptic ulcer.
Adverse Effects
 Abdominal cramps (sever colicky pain).
 Diarrhea.
 Uterine contraction dysmenorrhea or
abortion.
 Vaginal bleeding.

56. 3. Colloidal Bismuth compounds
Bismuth subcitrate
Tripotassium dicitrato bismuthate.
Mechanism of Action
1. It forms a precipitate with mucous cover the
ulcer with a protective coat that prevent effect of
HCl.
2. Promote healing of ulcer.
3. Bactericidal effect against campylobacter pylori .
4. Decrease activity of pepsin
5.  Mucous & bicarbonate secretion.

57. Adverse Effects
1. Black stool.
2. Teeth discoloration.
3. Encephalopathy (in renal dysfunction).
USES
1. Triple therapy for eradication of H. pylori.
2. Benign gastric & duodenal ulcer.
3. Traveller’s diarrhea

58. Drugs That Neutralize HCL (Antacids)
Drugs used to relief gastric pain associated with
hypersecretion of HCL.
Mechanism of Action
 Neutralization of HCL.
 Inhibition of pepsin (inactive at PH 5).
Therapeutic Uses
1. relief pain of peptic ulcer.
2. Dyspepsia.

59. I - Systemic Antacids
Sodium bicarbonate
NaHCO3 + HCL  NaCL + CO2.
Disadvantages
1. Rebound hyperacidity.
2. Stomach distension due to CO2 liberation 
pain sensation.
3. Sodium load  salt and water retention
( # in cardiac patients).
4. Systemic alkalosis.

60. Calcium Carbonate
CaCO3+HCL  CaCl2 + H2O + CO2
Disadvantages
1. Liberation of CO2  stomach distension
2. 10% is absorbed  hypercalcemia.
3. Rebound hyperacidity.
4. Milk alkali syndrome (hypercalcemia, renal failure).

61. II – Non Systemic Antacids
1. Aluminum Hydroxide Gel
2. Magnesium Trisilicate
Al (OH)3 + HCL  HCL3 + H2O.
Advantages
1. Longer duration of action.
2. Gradual neutralization of HCL  No rebound
hyperacidity.
3. Adsorbs pepsin.
4. Minimal change in acid base balance.
5. No stomach distention

62. Disadvantages
Al (OH)3
1. Constipation.
2. Drug interaction:  absorption of tetracycline,
digoxin, iron.
Magnesium Trisilicate
1. Diarrhea
2. CNS depression (renal failure).

63. Alginates (Gaviscon)
Combine with antacids in reflux esophagitis to
increase adherence of mucus to esophageal mucosa.