Peptic ulcer disease is defined as a discontinuity in the gastric or duodenal mucosa exposed to acid and pepsin secretion. Common causes include H. pylori infection, NSAID use, and stress. H. pylori infection is associated with 95% of duodenal ulcers and 80% of gastric ulcers. NSAID use inhibits prostaglandins, which protect the gastric mucosa. Treatment involves antibiotics to eradicate H. pylori, PPIs to reduce acid secretion, and medications to protect the gastric lining such as sucralfate. Triple therapy with a PPI and two antibiotics is the standard treatment to eradicate H. pylori.

4. Peptic Ulcer Disease

5. Definition
‘’Condition in which there is a discontinuity
in the entire thickness of the gastric or
duodenal mucosa that persists as a result
of acid and pepsin in the gastric juice’’
•The term peptic ulcer applies to mucosal
ulceration near the acid bearing regions of
GIT.
• Peptic ulcer disease (PUD) = Mucosal
defect in the GIT (gastric or duodenal)
exposed to acid and pepsin secretion.

6. Disease Prevalence
• Lifetime Prevalence = 10% of Americans
develop PUD.
• 10% of GERD patients with abdominal
pain diagnosed with PUD.
• Prevalence decreasing over last 30yrs.
• Male-to-female ratio of gastritis = 1:1
• Male-to-female ratio of PUD = 2:1

7. Gastric Ulcer
• Epigastric pain occurring 30
minutes to 1 hour after meals.
• Aggravated by eating
(because acid secretion
increase at meal time) leads to
weight loss.
• Relieved by vomiting (because
acid is expelled out).
• No pain at hours of sleep (HCL
production decreases at hours
of sleep).
• More common in persons older
than age 50.
Duodenal Ulcer
• Epigastric pain occurring 2-3
hours after meals.
• Relieved by food (because the
pyloric sphincter, at the
junction of stomach and
duodenum, closes upon eating
to concentrate food in the
stomach) causes weight gain.
• Not relived.
• Pain at hours of sleep
(because gastric emptying
continuous at hours of sleep).
• More common between age 25
and 50.

9. Epigastric region

10. • PUD develop only in
presence of acid
environment.
• Excess of gastric acid is
not necessary for ulcer development.
• Person with a gastric ulcer has normal
to less than normal gastric acidity
compared with person with a duodenal
ulcer.
• Some intraluminal acid does seem to
be essential for a gastric ulcer to occur.

11. Dyspepsia
• Dyspepsia is defined as persistent or
recurrent pain or discomfort centered in
the upper abdomen
• Peptic ulcer presents as dyspepsia
• Not all patients with dyspepsia have PUD
• Most common causes of dyspepsia are
non-ulcer or GERD and peptic ulcer.
• Other causes include gastric cancer,
pancreatic or biliary disease

12. Etiology and Pathophysiology
• Pepsinogen is activated to pepsin in
presence of HCl and a pH of 2 to 3.
• Secretion of HCl by parietal cells has a
pH of 0.8.
• pH reaches 2 to 3 after mixing with
stomach contents.
• Surface mucosa of stomach is renewed
about every 3 days.
• Mucosa can continually repair itself
except in extreme instances.

13. Etiology and Pathophysiology
• Mucosal barrier prevents back diffusion
of acid from gastric lumen through
mucosal layers to underlying tissue.
• Mucosal barrier can be impaired and
back diffusion can occur.
• HCL freely enters mucosa when barrier
is broken
• Result:
–Injury to tissue occurs
–cellular destruction and inflammation

14. Back diffusion of acid

15. Disruption of Gastric Mucosal Barrier

18. • H.pylori
• NSAIDs (even at low dose)
• Coffee/Caffeine
• Ethanol
• Tobacco
• Severe physiologic stress (Burns, CNS
trauma, Surgery, Severe medical illness)
• Steroids
Common Risk
Factors.

19. Symptoms
• Abdominal pain is the most common symptom of
the Peptic Ulcer.
• Other possible symptoms include:
– Nausea
– vomiting
– Weight loss
– Fatigue
– Heartburn
– indigestion
– Chest pain
– Blood in vomiting
– Bloody or dark tarry stools

21. Common form of PUD
1: H-PYLORI associated ulcer.
2: NSAIDs associated ulcer.
3: STRESS ulcer.

22. Helicobacter pylori
• Gram –ve microaerophillic
bacterium found in gastric
antrum of human stomach.
• 95% duodonal ulcer and
80% of gastric ulcers are
associated with H.pylori.
• The effect of H.pylori in
patients receiving NSAIDs
is unclear.

23. Helicobacter pylori's initiation
of mucosal inflammation

24. MECHANISM of H-Pylori
• To avoid the acidic environment of the interior of the
stomach H-pylori uses its flagella to burrow into the
mucus lining of the stomach to reach the epithelial cells
where there is a more neutral pH.
• H. pylori is able to move towards the less acidic region (
chemotaxis).
• H. pylori is found in the mucus on the inner surface of
the epithelium and occasionally inside the epithelial cells
themselves. It adheres to the epithelial cells by
producing adhesins which bind to lipids and
carbohydrates in the epithelial cell membrane.

25. MECHANISM of H-Pylori
• H. pylori causing peptic ulcer disease may
be more virulent than in those without
ulcers
• It produces cytotoxin associated gene A
proteins and vacuolating cytotoxins such
as vac A, which activate the infalmmatory
cascade
• Gene A and vac A are the predictors of
the ulcerogenic capacity of the strain

26. Mechanism of H.pylori
• Gastrin conc. is also increased in H.pylori
infection which causes hypergastrinaemia
• High acid content in the proximal
duodenum leads to metaplastic gastric-
type mucosa, which provides a place for
H. pylori infection followed by inflammation
and ulcer formation

27. MECHANISM of H-Pylori
• H. pylori also neutralizes the acid in its environment. It
does this by producing large amounts of urease which
breaks down the urea present in the stomach to
carbon dioxide and ammonia.

28. Discovery of Helicobacter pylori
• “Two Australian physicians won the 2005
Nobel Prize in Medicine or Physiology for
showing - at least partly by accident -- that
many ulcers are the result of a bacterial
infection.”
“Robin Warren
and Barry
Marshall's work
on ulcers was
pioneering”

29. NSAIDs
• Approximately 15% of patients on long-term
NSAID develop PUD.
• NSAIDs - ↓prostaglandin (PG) by inhibiting the
cyclooxygenase (COX) enzymes.
• Three iso-enzymes COX-1, COX-2, COX-3
• COX-1 → PG production in gastric mucosa.

30. NSAIDs associated ulcer
• NSAID induced peptic ulcers are the ulcers in
stomach or first part of doudenum which are
associated with the intake of Non-steroidal anti-
inflammatory drugs.
• Patients with Rheumatide Arthritis and
Osteoarthritis taking NSAIDs have an ulcer
incidence of approximately 15-20%.
• The overall risk for serious adverse GI events in
patients taking NSAIDs is about three times
greater than that of controls.
• In elderly patients (>60), this risk rises to 4-5
times than that of control.

31. PREVENTION
• Patients at high risk for hemorrhage and
perforation from aspirin and other NSAID-
induced ulcers should be considered for
prophylaxis with misoprostol.
• Proton pump inhibitors are an acceptable
alternative for prevention of NSAID-related
complications.

32. Treatment of NSAID induced Ulcer
• The medications may include one or more of the
following:
– Antibiotics to kill Helicobacter pylori.
– H2 blockers (like Famotidine (Zepsin),
Ranitidine, or Cimetidine).
– Proton pump inhibitors (such as Omeprazole)
– Medications that protect the tissue lining (like
Sucralfate).
– Bismuth (may help protect the lining and kill
the bacteria).

33. Individual NSAID Risk
High Risk
• Piroxicam/Feldene®
• Ketorolac/Toradol®
• Indomethacin/
Indocin®
Lower Risk
• COX-2 specific -
Celebrex®
• Ibuprofen (< 1500mg/d)
• Relatively selective COX-2
nabumetone/Relafen®
etodolac/Lodine®
meloxicam/Mobic®

34. Differentiating between H. pylori
and NSAID-induced ulcer
H. pylori
• more often in
duodenum.
• Often
superficial.
• less severe GI
bleeding.
• More
symptomatic.
NSAIDs
• more often in
stomach.
• often
deep.
• more severe
GI bleeding.
• sometimes
asymptomatic
STRESS
•In stomach.
•Most
superficial.
•Less severe
bleeding.
•Symptomatic.

35. Other Disease Conditions
Associated with PUD
• Hypersecretory states: Gastrinoma
(Zollinger-Ellison syndrome) or multiple
endocrine neoplasia (MEN-I).
• Diseases associated with increased risk of
PUD: cirrhosis, chronic pulmonary
disease, renal failure.

37. Physical Exam Findings
In uncomplicated PUD exam findings few
and non-specific:
• Epigastric tenderness - usually mild.
• Bowel sounds - normal.
• Signs of peritonitis with perforation.

38. Clinical manifestations
of Peptic ulcer disease

39. Lab Studies to Evaluate PUD
• CBC - evaluate acute/chronic blood loss.
• H. Pylori
- Serologic antibody test for HP – does not
determine if active HP infection.
- Fecal antigen test for active HP.
- Urea breath test for active HP.

40. Principles in Selecting
H. pylori Test
Based on the following:
• Probability of previously eradicated infection.
• Probability of current active infection.
• Need to document active infection.
• Need for rapid result.
• Patient preferences.
• Cost (both of test and possible unnecessary
treatment).

41. When is a Serology Test Useful?
Not useful in
• Populations with low
disease prevalence.
• Elderly populations to
detect active disease.
Useful in
• Patients who never
received H. pylori
treatment.
• Symptomatic patients
not using NSAIDs.

42. H. Pylori Stool Antigen (HpSa) Test
• Useful in initial diagnosis + confirmation of
eradication.
• Sensitivity of 91% and a specificity of 92%.
• Test requires collection of stool sample.
• Performed in lab.
• Requires little preparation, however patients
may not be compliant with collecting sample.

44. Urea Breath Test
• Useful for initial diagnosis + confirmation of
eradication.
• Sensitivity and specificity over 90%.
• Urease activity is present in the stomach in
those infected with H pylori.
• Ingest urea labeled with radioactive carbon.
• Hydrolysis of urea → labeled carbon dioxide
(CO2)
• Rapidly absorbed into bloodstream and within a
few minutes, appears in breath.

45. Urea breath test

46. Breath Test Compared to HpSa
• Requires more patient preparation.
• More expensive.
• Number of drugs can adversely affect accuracy .
• Antibiotics and bismuth → stop for 4 weeks.
• Proton pump inhibitors → stop for 7 days.
• Patients need to fast for at least 6 hours.
• Breath test cannot be used in pregnant women.

48. Imaging Studies
• Chest x-ray if perforation is suspected to
detect free abdominal air.
• Upper gastrointestinal series
– Performed by experienced radiologist is close
to diagnostic accuracy of endoscopy.
– Not as sensitive as endoscopy in diagnosis of
small ulcers (<0.5 cm).
– Unable to obtain biopsy to rule out
malignancy.

49. Imaging Study

50. Endoscopy
Endoscopy indicated in following high risk patients:
• >50 years old with new-onset dyspepsia.
• Dyspepsia with dysphasia(speech disorder) and
weight loss.
• Evidence of GI bleeding.
• Failed appropriate trial of empiric therapy.
• Using NSAIDs or other high risk medicines.
• Signs of UGI tract obstruction (vomiting).
• Ethnic background associated with increased
risk UGI malignancies.

52. TREATMENT

53. Over The Counter Remedies
• Aluminum and magnesium hydroxide salt
(Maalox®, Mylanta®) Neutralizes gastric
acidity.
• Aluminum side effect = constipation
• Magnesium side effect = diarrhea
• Magnesium and aluminum mixtures used
to avoid side effects.

54. • Calcium Carbonate (Tums®, Rolaids®) –
calcium salt neutralizes acid.
• Bismuth subsalicylate (Pepto-Bismol®) –
binds to ulcer base forming a protective
coat, has anti-inflammatory and
bactericidal properties.

55. H2-Blockers
• Selectively block H2-receptors on
parietal cells reducing acid secretion .
• Used primarily in ulcer disease not
associated with H pylori.
• Treatment duration is 6-8 week.

56. Side Effects of
Cimetidine/Tagamet®
• Elderly patients – confusion
• Young males - impotence
• May alter levels of other drug - warfarin,
TCA’s, triamterene, phenytoin, propranolol,
metronidazole, anti-arrythmics.
• May alter renal function so requiring lower
doses.

57. Proton Pump Inhibitors
• Decreases gastric acid secretion by inhibiting
the parietal cell H+/K+ ATP pump.
• Relieve pain and heal peptic ulcers more
rapidly than H2 blockers.
• Drugs in this class are equally effective.
• Four weeks to treat active PUD.

60. Other Pharmacotherapy Agents
• Sucralfate (Carafate®) Binds proteins in
exudates and forms a viscous adhesive that
protects GI lining.
• Misoprostol (Cytotec®) Prostaglandin analog-
protects lining of GI tract by replacing depleted
prostaglandin E1. Prevents peptic ulcers in
patients taking NSAIDs.

62. H. Pylori Triple Therapy Treatment
• Triple therapy for 14 days is treatment of
choice.
• Two forms of triple therapy: PPI–based
and bismuth-based.
• PPI based = PPI + 2 antibiotics for 2 week
& continue PPI for additional 2 weeks.
• Bismuth based = bismuth subsalicylate +
2 antibiotics for 2 weeks with addition of
H2- blocker to optimize ulcer healing.

63. H Pylori Treatment
Side Effect Rating Cure Rate
Three Drug Regimens
Clarithromycin500mg +
Metronidazole500mg BD + PPI 20-
40mg
medium 80-90%
Amoxicillin1g + Clarithromycin 500mg
+ PPI 20-40mg
medium-low 80-90%
Amoxicillin 1gm + Metronidazole
500mg + PPI 20-40mg
medium 80-90%
Combination Products

64. Type Drug Selected Side Effects Comments
Antacids
Aluminum hydroxide
Calcium carbonate
Magnesium hydroxide
Sodium bicarbonate
Nausea, headache, weakness, loss of
appetite, constipation (aluminum
hydroxide) or diarrhea (magnesium
hydroxide)
Used mainly to relieve
symptoms, not as a cure
Histamine-2 blockers
•Cimetidine
•Famotidine
•Nizatidine
•Ranitidine
Rash, fever, muscle pains; may cause
breast enlargement and erectile
dysfunction in men; may interfere with
elimination of certain drugs (cimetidine);
confusion (cimetidine, ranitidine)
The once-daily dose is taken in
the evening or at bedtime;
doses taken in the morning are
less effective
Proton pump inhibitors
•Lansoprazole
•Omeprazole
•Pantoprazole
•Rabeprazole
•Esomeprazole
Diarrhea, constipation, headache Usually well tolerated; most
effective means of reducing
stomach acid
Antibiotics
•Amoxicillin
•Clarithromycin
•Metronidazole
•Tetracycline
Diarrhea (amoxicillin, clarithromycin,
tetracycline), altered taste, nausea
Effective for treating peptic ulcers
caused by Helicobacter pylori
infection
Miscellaneous
Bismuth subsalicylate
•Misoprostol
•Sucralfate
Diarrhea (bismuth subsalicylate,
misoprostol); darkening of the tongue
and stool (bismuth subsalicylate);
spontaneous abortion (misoprostol);
constipation (bismuth subsalicylate);
may reduce effectiveness of other
drugs (sucralfate)
Bismuth subsalicylate is used in
combination with antibiotics to cure
H. pylori infection

65. H Pylori Treatment

67. PUD Complications
• Hemorrhagic shock from a perforated
ulcer.
• Symptomatic relief with PPI may mask
symptoms of gastric malignancy.
• Gastritis may present as bleeding, more
likely in elderly.
• Symptoms of anemia (fatigue, dyspnea).

68. Initial Treatment Plan in the
Absence of High Risk Symptoms
Based on current evidence, no single
strategy has been demonstrated to be
more medically effective than any other.
• Empiric therapy with acid suppression.
• Empiric H pylori testing and treating
strategy.
• Early endoscopy.

69. Final Recommendations
• Alarm symptoms = endoscopy.
• No alarm symptoms = medical
management favored approach.
• Studies still in progress to evaluate if
medical management versus endoscopy
is both medically and cost effective in
long-term.
• Lack of response or the recurrence of
symptoms warrants endoscopy.

70. Medical Legal Pitfalls
• Failure to consider non-GI cause of epigastric
pain.
• Failure to consider GI bleed in absence of
abdominal pain (especially in elderly).
• Lack of follow-up care resulting in failure to
diagnose gastric cancer.
• Failure to recommend endoscopy early in high
risk patients.
• Failure to obtain a history regarding NSAID use.

71. References:
oClinical Pharmacy and Therapeutics by
Roger Walker.
oPharmacology by Lippon cott.
oClinical and Disease Management by Dr.
Inam Danish.
oPharmacotherapy Hand Book.
oGoogle and Wikipedia.

72. Any
QUESTION ?