1. Definitions: Stomach or duodenal mucosal lesions
PEPTIC ULCER
Definitions: Stomach or duodenal mucosal lesions
Occurrence: due to imbalance between aggressive factors and mucosal protective mechanisms.

2. Pepsin secretion - acid secretion Protective factors
PEPTIC ULCER
Aggressive factors
Pepsin secretion - acid secretion
Protective factors
Prostaglandins (E2 & I2 )
Mucus/bicarbonate secretion
Mucosal blood flow
Rapid turnover of gastric mucosa

3. Risk factors H Pylori infections Alcohol Smoking Diet
Drugs (NSAIDs, corticosteroids).
Stress
Genetic factors
Diseases (Zollinger Ellison Syndrome).

4. SYMPTOMS: Nausea – Vomiting – Anorexia Upper abdominal pain.
Weight loss.
Heart burn.

5. COMPLICATIONS: Gastrointestinal hemorrhage
Chronic iron deficiency anemia
Pyloric stenosis
Perforation

6. Gastric secretions Pepsinogens (Chief cells).
HCl and intrinsic factor (Parietal cells).
Gastrin (G-cells).
Mucus, bicarbonate (mucus-secreting cells).

7. Regulation of Gastric secretions
Histamine (local hormone)
Acetylcholine (neurotransmitter).
Gastrin (hormone).

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

11. I. Gastric hyposecretory drugs.
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

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

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

14. 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:
Omperazole
Lansoprazole
Pantoprazole

15. Illustration of Gastric secretion by parietal cells

16. 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).

17. 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.

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

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

20. 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

21. 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

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

24. 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.

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

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

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

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

29. Pirenzepine - Telenzepine
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.

30. 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.

31. Helicobacter pylori in association with gastric mucosa

32. 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.

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

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

35. Mucosal protective agents.
Sucralfate
Prostaglandin analogues.
Colloidal bismuth

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

37. 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.

38. 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.

39. 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.

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

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

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

43. 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
relief pain of peptic ulcer.
Dyspepsia.

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

45. 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).

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

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

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