overview of peptic ulcer with detailed information on their drugs used in treatment peptic ulcer , pharmacological action, mechanism, uses and adverse effect for both medical and dental students.

1. Peptic ulcer disease
BY : BIBI UMEZA

2. What is PEPTIC ULCER?????
 Breaks in mucosal surface
 >5mm in size
 Depth till submucosa
 In any part of GI tract exposed to aggressive
action of acid pepsin juices.
 Can be acute or chronic
 Both can penetrate muscularis mucosae..

3. SITES
 Gastric and duodenal – 98 %
 Ratio of 1:4
 Duodenum:1st part >95% :ant & post walls
 Gastric :junction b/w antrum &acid secr. mucosa :lesser curvature

4. Why Peptic ulcer occurs ?
 Imbalance between Aggressive factors and
Defensive factors

5. Regulation of gastric acid secretion

7. ETIOLOGY
 Predisposing factors
– Age :young in DU and GU.
– Sex :GU commoner in males
 Causes
– H.Pylori
– NSAID
– Infection: herpes simplex,etc..
– Other drug/toxin: bisphosphonates ,glucocorticoids

8. Pathogenetic factors not related to
h.pylori & NSAID
 Smoking
 Genetic : blood group O
 Stress
 Diet : alcohol and caffeine

9. Associations
 Systemic mastocytosis
 Nephrolithiasis
 Hyperparathyroidism
 Cirrhosis
 Alpha antitrypsin deficiency
 Pancreatitis, polycythaemia vera

10. Pathogenesis
 Related with NSAIDs
 Topical NSAIDs.
NSAIDs migrate across lipid membrane of epithelial cells.
Trapped in an ionized form
Related with NSAIDs Cell injury
Alter surface mucous layer.
Peronits back diffusion of H+ & Pepsin.
Further cell damage.

11. Figure shows machanisms by which
NSAIDs may induce mucosal injury :

12. Risk factors for NSAID – induced
Gastroduodenal ulcers
 Established
 Advanced age.
 History of ulcer.
 Concomitant use of glucocorticoids.
 High dose of NSAIDs.
 Multiple NSAIDs.
 Concomitant use of anticoagulants
serious or multi system disease.
 Possible
 Concomitant infection with H. pylori.
 smoking.
 Alcohol consumption.

13. Phathogenesis of H.pylori

14. Types of peptic ulcer
Acute peptic ulcer
Chronic peptic ulcers
- Gastric ulcers
- Duodenal ulcer

15. Acute peptic ulcer
 Ingestion of Aspirin or butazolidin.
 By stress (Stress ulcer):-
 May be following endotoxic
shock :
-Hypotension,
-Hemorrhage or
-Cardiac infarction

16. Acute peptic ulcer
 Sepsis.
 After trauma or neurosurgical operations (Curling’s ulcers).
 After burns (curling’s ulcers).
 Patient on steroids
The size of peptic ulcer (Steroids ulcers).

17. CHRONIC PEPTIC ULCERS
 GASTRIC ULCERS
 . Decrease mucosal resistance.
 . Pyloroduodenal reflex.
 . Deficient mucous barriers.
 . Mucosal trauma.
 . Local Ischaemia.
 . Antral stasis.
 . NSAIDs.
 . Helicobacter pylori.

19. DUODENAL ULCER
 Acid hyper secretion.
 . Genetics factor.
 . Endocrine organ dysfunction.
 . Liver abscess.
 . Emotional factors.
 . Diet & smoking.
 . Helicobacter pylori.
 . Decrease in bicarbonate production.

21. Pathophysiology Gastric ulcer Duodenal ulcer
Major causes H.pylori & NSAID H.pylori & NSAID
Gastric acid decreased increased
Gastric emptying delayed rapid
Abnormal resting & stimulated
Pyloric sphincter pressure
Bicarbonate secretion remarkably
decreased

22. Clinical features
 Abdominal pain*
•Epigastric
•Burning or discomfort
•Awakes from sleep
 Nausea
 Weight loss
 Dyspepsia if not relieved by antacids —penetrating ulcer

23. Treatment ?

25. H2 ANTAGONISTS

26. Mechanism of action
Competitively block H2 receptors on parietal
cell & inhibit gastric acid production
Suppress secretion of acid in all phases but
mainly nocturnal acid secretion
Also reduce acid secretion stimulated by
Ach, gastrin, food, etc.

27. Pharmacokinetics
 Absorption is not interfered by food
 Can cross placental barrier and reaches milk, Poor CNS
penetration
 The serum half-lives range from 1.1 to 4 hours;
 Cleared by a combination of hepatic metabolism, glomerular
filtration, and renal tubular secretion.
 Dose reduction needed in moderate to severe renal
insufficiency

28. Comparison of H2 antagonists

29. H2 antagonists - Uses
Promote the healing of gastric and duodenal ulcers
 Duodenal ulcer – 70 to 90% at 8 weeks
 Gastric Ulcer – 50 to 75%
 NSAID ulcers induced ulcers
 Stress ulcer and gastritis
 GERD
 Zollinger-Ellison syndrome
 Prophylaxis of aspiration pneumonia

30. Adverse effects
 Headache, dizziness, bowel upset, dry mouth
 CNS: Confusion, restlessness
 Bolus IV – release histamine – bradycardia,
arrhythmia, cardiac arrest
 Cimetidine has antiandrogenic actions

31. Proton Pump Inhibitors
 Most effective drugs in antiulcer therapy
 Prodrugs requiring activation in acid environment
 Activated forms binds irreversibly to H+K+ATPase and
inhibit it
Omeprazole
Pantoprazole
Lansoprazole
Esomeprazole

32. Mechanism of Action
 Prodrugs inactive at neutral pH
 At pH < 5 rearranges to two charged
cationic forms (sulfenamide + sulphenic acid)
that bind covalently with SH groups of H⁺K⁺
ATPase and inactivate it irreversibly
 Also inhibits gastric mucosal carbonic
anhydrase

33. Pharmacokinetics - PPI
 Available as enteric coated tablets
 They should be given 30 minutes to 1 hour before
food intake
 half life is very short and only 1-2 Hrs
 Still the action persists for 24 Hrs to 48 hrs after a
single dose
 Action lasts for 3-4days even after stoppage of the
drug

35. Therapeutic uses:
 1. Gastroesophageal reflux disease (GERD)
 2. Peptic Ulcer - Gastric and duodenal ulcers
 3. Bleeding peptic Ulcer
 4. Zollinger Ellison Syndrome
 5. Prevention of recurrence of nonsteroidal antiinflammatory drug (NSAID)
- associated gastric ulcers in patients who continue NSAID use.
 6. Reducing the risk of duodenal ulcer recurrence associated with H. pylori
infections
 7. Aspiration Pneumonia

36. Adverse Effects
 Nausea, loose stools, headache abdominal pain,
constipation,
 Muscle & joint pain, dizziness, rashes
 Rare :
Gynaecomastia, erectile dysfunction
Leucopenia and hepatic dysfunction
Osteoporosis in elderly on prolonged use
Hypergastrinemia

37. Drug interactions
 Omeprazole inhibits the metabolism of
warfarin, phenytoin, diazepam, and
cyclosporine.
 However, drug interactions are not a problem
with the other PPIs.

38. PPI – Dosage schedule
 Omeprazole - 20 mg o.d.
 Lansoprazole - 30 mg o.d.
 Pantoprazole - 40 mg o.d.
 Rabeprazole - 20 mg o.d.
 Esomeprazole - 20-40 mg o.d

39. Proton Pump Inhibitors
 Lansoprazole :
Partly reversible, more potent, slightly more against
H.pylori, Higher BA, rapid onset.
 Pantoprazole:
More acid stable, I.V, CYP450 less affinity
 Rabeprazole:
claimed to most rapid
 Es-omeprazole
Better intragastric pH , higher healing rates.

48. Antacid - Interactions
 Absorb drugs and form insoluble complexes that are
not absorbed
 Clinical importance : Interactions can be avoided by
taking antacids 2 hrs before or after ingestion of
other drugs .

49. Now answer this question
Is it rational to combine Aluminium
hydroxide and Magnesium hydroxide
in antacid preparations ?

52. Systemic antacids
 • Soluble instant short duration
 • But cause systemic alkalosis
 • So other uses
– Metabolic acidosis
– Alkalinisation of urine
– Antipruritic lotion,eye wash,mouth wash

54. Adverse effects
 constipation,
 hypophosphatemia
 • Other uses
–Bile reflux Gastritis Stomatitis
–Prophylaxis of stress ulcers

57. US FDA Approved Regimen
 • Lansoprazole 30mg
 • Amoxicillin 1000mg
 • Clarithromycin 500mg
Twice daily Two weeks

58. Regimen popular in India
 • Metronidazole 400mg TDS
 • Amoxicillin 500 mg TDS
 •Omeprazole 20 mg BD For 1 week

59. Quadruple Therapy
 Given when Triple Therapy fails
 CBS - 120 mg qid
 Omeprazole / Lansoprazole - 20 / 30 mg bd
 Metronidazole - 400 mg TDS Tetracycline - 500 mg
qid

60. Thank You