1. In the name of God Peptic Ulcer Disease
By: E. Salehifar
(Clinical Pharmacist)

2. Peptic Ulcer Disease (PUD)
PUD: 10% of the people in their lifetime
Prevalence of active disease: 1-2%
Duodenal ulcers
Gastric ulcers
Others: Ulcers of esophagus
Zollinger-Ellison
(gastrin-producing tumor)

3. Upper Gastrointestinal Disorders
Dyspepsia
25-55% of the people in their lifetime
Abdominal pain or discomfort
Symptoms of early satiety, bloating, nausea & vomiting
Nonulcer Dyspepsia: 60%
PUD: 20%
GERD: 20%

4. GERD
Backflow of GI contents into the esophagus resulting in esophagitis
Classic symptom: Heartburn or burping up of stomach contents into the mouth
Major concern: Barrett’s esophagus
(a predisposing factor for esophagus cancer)

5. Mucus secreting cells
Body:
Parietal cells (H+, IF),
chief cells (Pepsinogen)
Antrum:
G cells (Gastrin)

6. Stomach physiology Fundus (mucus-secreting cells) Body (80-90%)
Parietal cells (acid, intrinsic factor)
Chief cells (pepsinigen)
Antrum (10-20%)
G cells (gastrin)

8. Regulation of acid secretion
Increase
ACH
Histamine
Gastrin
Decrease
PGE
Cholecystokinin
Glucagon
VIP

9. Helicobacter pylori (HP)
What is the cause of PUD?
No acid, No Ulcer! (PH)
Helicobacter pylori (HP)
NSAIDs
Cigarette Smoking

10. HP: A Gram negative spiral bacteria

11. HP Was isolated in 1983 (Campylobacter pylori)
Infection is more common in older individual
Person to person transmission
Is found most consistently in gastric antrum
pathogenesis: Urease (↑NH3), cytotoxin, inflammation, breakdown of mucosal defense

12. Why HP is implicated in PUD?
90% of PUD, in the absent of NSAIDs exposure, are associated with HP
Is found in 90% of DU & 70% of GU patients
Eradication of HP accelerates the ulcer healing and decreases the recurrence rate
PUD in HP negatives is rare

13. HP: Is not a single cause of PUD!
HP positive: 50-90% of general population
15-30%: PUD
20-40%: Nonulcer dyspepsia
30-65%: Asymptomatic
HP infection is not associated with acute perforated DU

14. When PUD occurs? Aggressive factors Defensive factors HP H+ Pepsin
NSAIDs (Direct, ↓PGE)
Smoking
(↑H+ & bile salt reflux, ↓PGE & mucosal blood flow)
Defensive factors
PGE
Somatostatin
Mucus
HCO3¯
Mucosal blood flow
Rapid regeneration
Resitution

17. Clinical presentation
The most common symptom: epigastric pain
Pain is not well localized
DU pain commonly occurs with empty stomach and relieves by food and antacid
GU pain occurs at any time frequently immediately or 1-3 hours after a meal

18. Clinical presentation (continue)
Pain dose not always correlate with ulcer especially in elderly taking analgesics and in patients with high pain tolerance
Other symptoms: nausea, vomiting, belching, bloating & anorexia
endoscopy is needed for definitive diagnosis

19. PUD: Is there any role for foods?
Caffeine, milk, alcohol, spicy foods increase acid secretion and cause dyspepsia, but they can not increase risk of PUD
Acute alcohol ingestion can damage the gastric mucosa, leading to GI bleeding, however alcohol has not been proven to cause PUD

20. PUD: Genetic association
20-50% of patients with DU have a positive family history of PUD

21. PUD: Association with Stressful life
Stressful life events thought by some to exacerbate PUD

22. Epidemiology (incidence & prevalence)
Increase in PUD during the beginning of the 20th century with a peak in 1950s
Over the past 2 decade, DU have declined (both outpatient & inpatient episodes)
GU has remained stable perhaps due to aging & use of ulcerogenic drugs

23. PUD (Geographic variation)
In Japan, GU is 5-10 times more common
In the US & European countries, DU is 2 times more common

24. PUD (gender)
In 1968, rate of PUD in men was twice, but now is similar for men & women
Hospitalization of women with GU have increased markedly for patients older than 65

25. PUD (age)
GU is rare before age 40, and the peak incidence occurs from ages 55-65
The incidence of DU increase with age until the age of 60 years

26. PUD (morbidity & mortality)
Mortality of PUD has declined during the past 20 years
Less than 2% of patients receiving therapy are expected to have a complication
One of the most common GI diseases that results in loss of work and high-cost service

27. Comparison of DU & GU GU DU Rare before 40 Increases with age
Common in Japan
Normal or low acid
Normal or sl. ↑ gastrin
Normal parietal cell mass
No genetic influence
No ↓ in incidence
No ↑frequency in cirrhosis
More common in blood A DU
Increases with age
Common in US
Hyperacidity
Hypergastrinemia
↑ parietal cell mass
Genetic influence
Incidence ↓
↑ frequency in cirrhosis
More common in blood O

28. Treatment Goals Relief of symptoms Promotion of ulcer healing
Prevention of ulcer recurrence and complications

29. Treatment Eradication of HP (seropositive DU & GU)
Acid suppression (DU)
PPIs
H2-blockers
Antiacids
Enhancing mucosal defenses (GU, DU) Sucralfate

30. Treatment In HP (+) patients: In HP (–) patients: Eradication of HP
H2 blockers, Sucralfate & antacid are equally effective, but H2 blockers are much easier to use with less drug interactions
PPIs may be slightly more effective than H2 blocker and should be reserved for refractory cases

31. H2 Blockers Cimetidine (Tagamet) B Tab: 200mg, Inj: 200 mg/2ml
Ranitidine (Zantac) B
Tab: 150 mg, Inj: 50 mg/2ml
Famotidine B
Tab: 20 mg, 40 mg

32. H2 Blockers (indications)DU GU
GERD ZE
have equal efficacy (70-95% healing rate after 4-8 weeks of therapy)
Potency & duration of action of famotidine (& nizatidine) is greater, but all can be used once daily
In GERD, all H-2 blockers should be used before meals

33. H2 Blocker dosage for DU & GU
Cimetidine: 300 mg QID, 400 mg BD, 800 mg HS
Ranitidine: 150 mg BD, 300 mg HS
Famotidine: 20 mg BD, 40 mg HS
-Dosage adjustment in moderate to severe renal insufficiency
-Sr Cr may increase with cimetidine

34. H2 Blockers (Adverse Effects)
Are remarkably safe
Common: GI (diarrhea, constipation),
CNS (confusion, headache, dizziness, drowsiness), Rash
Gynecomastia & Impotence: Cimetidine
Heptotoxicity: Ranitidine

35. Drug interactions Cimetidine: Phenytoin, Warfarine, theophylline
Cimetidine & Ranitidine: Procainamide & NAPA (↓tubular secretion)
All H2-Blockers: Ketokonazole, Fe

36. Proton pump inhibitors (PPIs)
Omeprazole (Prilosec®) Cap: 10, 20 mg
Lansoprazole (Prevacid®) Cap: 15, 30 mg
Rabeprazole (Aciphex®) Tab: 20 mg
Pantoprazole (Protonix®) Tab: 20, 40 mg
- PPIs relieve symptoms and heal ulcer more quickly than H2 Blockers (2-4 W compared to 4-8 W)

37. PPIs (Pharmacokinetic)
Enteric-coated granules within capsule
Bioavailability: 30-80%
Omeprazole & lansoprazole are prodrugs for O. sulfonamide, L. sulfone, hydroxy lansoprazole
Despite the short t1/2, antisecretory effects is present 72 hr
No dosage adjustment in renal disease

38. PPIs (ADRs) ADRs are relatively negligible
Include GI (nausea, diarrhea, abdominal pain), CNS (dizziness, headache), rash, gynecomastia, ↑ SGOT, SGPT
No risk of hyperplasia and carcinoid tumor in spite of hypergastrinemia

39. PPIs (Drug Interactions)
Omeprazole decreases metabolism of diazepam, phenytoin, warfarin (2C9)
Less interaction with Lansoprazole
Pantoprazole also is metabolized by sulfotransferase, it appears to interact less with cyp450
Rabeprazole can modestly increase Dig

40. Sucralfate (Carafate®)
Protects ulcerated tissue from aggressive
factors (pepsin, acid, bile salts)
PH → forms a physical barrier to injury
Not absorbed systemically
Other protective actions on the mucosa
(PG, bicarbonate)
Duodenal ulcer (active, maintenance) & Gu

41. Sucralfate (ADR)
Constipation
Dry mouth
Nausea
Rash

42. Eradication of H.Pylori
Monotherapy not recommended
PPI or bismuth + two antibiotics
Amoxicillin
Clarithromycin
Metronidazole
Tetracycline

43. OCA (10 days) Omeprazole: 20 mg BD Clarithromycin: 500 mg BD
Amoxicillin: 1000 mg BD

44. LAC (14 days ( Lansoprazole 30mg bid before meals
Amoxicillin 1000mg bid with meals
Clarithromycin 500mg bid with meals

45. OC
Omeprazole 20mg BID, 30days
Clarithromycin 500mg TID, 14days

46. LCM, OCM (14 days)
PPI: (Lansoprazole 30 mg BD or Omeprazole 20 mg BD), 2 weeks
Clarithromycin: 500 mg BD, 2 weeks
Metronidazole: 500 mg BD, 2 weeks

47. Summary Importance of HP in development of PUD
Clinical symptoms of DU & GU
Treatment principles