This document provides an overview of current trends in the management of peptic ulcer disease. It defines peptic ulcer disease and discusses its classification, symptoms, history, epidemiology, etiology, anatomy, pathophysiology, diagnosis, complications, and management. Key points include that Helicobacter pylori infection and NSAID use are the primary risk factors, proton pump inhibitors are the first-line treatment, and treatment aims to relieve symptoms, promote healing, eradicate H. pylori if present, prevent recurrence, and avoid complications.

1. CURRENTTRENDS IN THE MANAGEMENT OF
PEPTIC ULCERDISEASE (PUD)
De-Graft Gyamfi Adjei
1

2. OUTLINE
• INTRODUCTION
– DEFINITION
– HISTORY
• EPIDEMIOLOGY
• ETIOLOGY
• ANATOMY
• PATHOPHISIOLOGY
• CLINICAL PRESENTATIONS
• INVESTIGATIONS
• MANAGEMENT
• ACKNOWLEDGENT
• REFERENCES
2

3. INTRODUCTION
• Peptic ulcer refers to a break in the lining of
the stomach, first part of the small intestine or
occasionally the lower oesophagus.
3

4. CLASIFICATION OF PEPTIC ULCER
DISEASE
• The major forms of PUD are:
– Gastric Ulcer
– Duodenal Ulcer
• Gastric Ulcer: ulcers that occur in the stomach
• Duodenal Ulcer: ulcers that occur in the upper
area of the small intestine
4

5. SYMPTOMS OF DUODENAL ULCERS
• Localized pain(pin point), restricted to mid-epigastrum
• Nocturnal pain
• Relieved by food and antacids
• Pain may radiate to costal margins of the back or the
right shoulder
• Weight gain (probably due to ↑ urge to eat to relieve
pain)
5

6. SYMPTOMS OF GASTRIC ULCERS
• Pain is more diffuse – over a wide area of mid
epigastric region
• Rarely produces nocturnal pain
• Pain precipitated by food
• Pain may be referred to the left subcostal region
• Weight loss common with GU
6

7. HISTORY
• EARLY 20TH CENTURY:
– Ulcers were believed to be caused by stress an
dietary factors.
– Later gastric acid was blamed for peptic ulcer
disease
7

8. …HISTORY
• 1982
– first identified the link between Helicobacter
pylori and ulcers.
• 1994
– NIHCDC concluded that there Is a strong link
between H. pylori and ulcer dxs
– Pxs be treated with antibiotics
8

9. …HISTORY
• 1996
– The FDA approves the first antibiotic for treatment
of ulcer disease
• 1997
– The CDC launches campaign to inform healthcare
providers and consumers about the link between
H. pylori and ulcers
9

10. EPIDEMIOLOGY
• In the US, PUD affects 4.5million people
annually
• Approximately 10% of the US population has
evidence of duodenal ulcer at some time,
• Of those infected with H. pylori, the lifetime
prevalence is approx. 20%
• Only about 10% of young persons have H.
pylori infection
10

11. EPIDEMIOLOGY
• Overall, the incidence of Duodenal ulcer has
been decreasing over the past 3-4 decades
• The prevalence of PUD has shifted from
predominance in males to similar occurences
in males and females
• In May 2014, WHO established that in Ghana,
the death rate due to PUD was 9.55 per
100,000 persons
11

12. EPIDEMIOLOGY(KBTH)
• Patience attendance at OPD
– 2013- 13744 persons
– 2014- 13051 persons
• Out of the above population, PUD cases were
587(4.2%) in 2013 and 1177(9.01%) in 2014
• Females represented 55-58% of the
population recorded
• <5% had surgery
12

13. EPIDEMIOLOGY(KBTH)
• At the endoscopy unit, 1144(36.0%) were
confirmed to have PUD in 2013
• PUD was ranked one of the top 10 causes of
admission for three consecutive years
• PUD was ranked the 9th major cause of admission(in
males) and 10th in females at the polyclinic
13

14. EPIDEMIOLOGY
0
20
40
60
80
100
120
140
2012 2013 2014
F
R
E
Q
U
E
N
C
Y
YEARS
TOP TEN CAUSES OF ADMISSION AT GENERAL SURGERY
14

15. ETIOLOGY
• The 2 most common risk factors for PUD are:
– Helicobacter pylori
– Non steroidal anti- inflammatory drugs
• Other uncommon risk factors include:
– Lifestyle factors(e.g ageing, smoking, alcohol intake)
– Severe physiologic stress
– Hypersecretory states
– Genetic factors
15

16. 1. ETIOLOGY-Helicobacter pylori
16

17. Helicobacter pylori
• H. pylori is a Gram-negative,
spiral & microaerophyllic
bacterium with multiple flagella
at one end
• Adheres to gastric epithelial
lining.
• Produces various enzymes -
urease, haemolysins, fusidase,
neuraminidase.
• About 2/3 of world population
infected , with an estimated
prevalence of 80-90 % in the
developing world
17

18. Helicobacter pylori
• Infected persons have
up to 6-fold increased
risk of developing
gastric cancers
• Most likely spread from
person to person
through faecal-oral and
oral-oral routes.
18

19. Pathogenesis of H. pylori infection
• The Flagella make it motile,
allowing it to live deep
beneath the mucus layer
• It uses an adhesin molecule
to bind to epithelial cells
Where the pH there is close
to neutral
19

20. 2. Etiology -Non-Steroidal Anti-inflammatory
Drugs (NSAIDS)
• Symptomatic GI ulceration
occurs in 2% - 4% of
patients treated with
NSAIDs for 1 year
• The effects of aspirin &
NSAIDs on the gastric
mucosa ranges from
mucosal hemorrhages to
erosions & acute ulcers
20

21. NSAIDS
• Inhibit the production
of prostaglandins
resulting in:
– 1. Decrease mucus &
HCO3 production
– 2. Decrease mucosal
blood flow
– 3. Reduce cell renewal
• HCl aggravates NSAID-
induced mucosal injuries
by
– Converting superficial
injury to deeper mucosal
necrosis,
– Interfering with
haemostasis & platelet
aggregation
– Impairing ulcer healing
21

22. Types of NSAID & Risk of Ulcer
22
Risk Group Drug
Low Ibuprofen
Medium Naproxen
Diclofenac
Indomethacin
High Piroxicam,Ketoprofen Azapropazone

23. PATHOPHYSIOLOGY
• The upper G.I system consists of
– Oesophagus
– Stomach
– Duodenum
• Stomach
– Cardia: secretion of mucous
– Body:
• parietal cells
• Chief cells
– Antrum:
• G cells
• D cells
23

24. PATHOPHYSIOLOGY
• Gastric Secretions (About 2.5L HCL daily)
• smooth muscle – churning
• sub-mucosa – veins and arteries that carries blood to the
liver
24

25. PATHPHYSIOLOGY
• The gastroduodenal mucosal integrity is
determined by adequate balance between
protective(defensive) and
damaging(aggressive) factors
• When the aggressive factors increase or the
defensive factors decrease, mucosal damage
will result leading to ulcerations
25

26. PATHOPHYSIOLOGY
• DEFENSIVE FACTORS
– Bicarbonate
– Mucus layer
– Mucosal blood flow
– Prostaglandins
– Rapid epithelial renewal
• AGGRESSIVE FACTORS
– Helicobacter pylori
– HCl
– NSAIDs
– Stress
– Smoking& alcohol
– Ageing
26

27. PATHOPHYSIOLOGY
27

28. PATHOPHYSIOLOGY
• Two major variants in peptic ulcers are commonly encountered in
the clinical practice:
1. Duodenal Ulcer (DU)
2. Gastric Ulcer (GU)
• DU: increased acid load to the duodenum due to:
• Increased parietal cell mass
• Increased gastrin secretion (e.g. Zollinger-Ellison syndrome, alcohol &
spicy food)
• H. pylori damaging somatostatin-producing cells
• Increased gastric emptying rate
• HCO3 secretion is decreased in the duodenum by H. pylori
inflammation
• Increased vagal nerve stimulation
28

29. PATHOPHYSIOLOGY
GU results from the break down of gastric mucosa:
1) The local epithelial damage due to cytokines released by H. pylori
2) Pyloric sphincter dysfunction or obstruction
3) Reflux of bile salts into the stomach
4) Nicotine- delaying ulcer healing
29

30. Pathogenesis of H. pylori infection
• Effects of H. pylori on gastric Hormones
30
- ↓ Somatostatin production from antral D-cells due to antral gastritis
- Low somatostatin will ↑Gastrin release from G-cell  hypergastrinemia
- This will stimulate acid production by the parietal cells  leading to further
duodenal ulceration.
This effect is exaggerated among smokers!

31. DIAGNOSIS
• Involves 3 Criteria
– Patient history taking
Risk Factors
Symptoms
– Clinical Signs
epigastric tenderness
GI bleeding
– Investigations
• Endoscopy for ulcer detection
• H. pylori Detection
31

32. DIAGNOSIS OF H. pylori
• Non-invasive
– C13 or C14 Urea Breath Test
– Stool antigen test
– H. pylori IgG titer (serology)
• Invasive
– Gastric mucosal biopsy with histology
– Rapid Urease test (CLO test)
32

33. DIAGNOSIS OF H. pylori
Non-invasive
1. C13 or C14 Urea Breath Test
33
The best test for the detection of an active infection

34. DIAGNOSIS
 Non-invasive
 Serology for H pylori
 Serum Antibodies (IgG) to H pylori (Not for active
infection)
 Fecal antigen testing (Test for active HP).
 Invasive
 Upper GI endoscopy
 Highly sensitive test
 Patient needs sedation
34

35. Endoscopy (Invasive)
 Detects the site and the size of the ulcer, even small and
superficial ulcer can be detected
 Detect source of bleeding
 Biopsies can be taken for rapid urease test,
histopathology & culture
35

36. Invasive (endoscopy)
 Rapid urease test ( RUT)
 Considered the endoscopic diagnostic test of choice
 Gastric biopsy specimens are placed in the rapid
urease test kit. If H pylori are present, bacterial urease
converts urea to ammonia, which changes pH and
produces a COLOR change
36

37. Duodenal Ulcer on Endoscopy
37
Normal duodenal bulb Duodenal Ulcer

38. Gastric Ulcer on Endoscopy
38
Chronic Gastric Ulcers

39. DU/GU ON ENDOSCOPY
39

40. PUD COMPLICATIONS
• GI bleeding
• Perforation
• Gastric /duodenal obstruction(presents with projectile vomiting,
pyloric stenosis)
• Haemorrhage –may lead to Chronic anemia
• Recurrence
• Malignancy- gastric ulcers
40
Bleeding DU Perforated GU Duodenal stricture

41. PUD COMPLICATIONS
41
OBSTRUCTION – PYLORIC STENOSIS

42. PUD and CANCER
• Vacuolating cytotoxins(vac A)
– Pore-forming proteins
– Permeability
– Suppresses immunity
• Cytotoxin associated gene
(cag A)
– Oncogenic proteins
– Changes morphology
– Apoptosis
42

43. INTERVENTIONS
• Surgical interventions may be required in certain cases
– Malignant ulcers
– Pyloric stenosis
– Chronic ulcerations
– Uncontrolled bleeding
– perforations
• 3 main surgical procedures
– Vagotomy
– Antrectomy
– Pyloroplasty
43

44. MANAGEMENT OF PEPTIC ULCER DISEASE
44

45. NON PHARMACOLOGICAL TREATMENT
• Avoid smoking/smoke cessation
• Avoid foods that aggravate the pain
• Allay anxiety and stress; reduced if possible
• Regular small meals
• Moderation of coffee and tea
• Avoid late night snacks as they stimulate nocturnal
gastric acid secretion
• Avoid alcohol
• Have enough rest
• Avoid NSAID’s when necessary
45

46. GOALS OF TREATMENT
• Pharmacological treatment
– To relieve pain and reduce gastric acid secretions
– To promote healing of the ulcer
– To eradicate H. pylori if present
– To prevent recurrence of ulcer
– To avoid complications
46

47. PEPTIC ULCER DRUGS
• Proton pump inhibitors (PPI)
• H2 – receptor antagonist
• Prostaglandin analogues
• Sucralfate
• Antacids
• BISMUTH CHELATES(no longer used ;
neurotoxic)
• Selective anti-muscaranics (Pirenzepine)
47

48. PROTON PUMP INHIBITORS- PPI’s
• PPI’s are weak bases and hence need enteric coating to
protect it from the acidic state of the stomach
• PPI’s bind irreversibly to the proton pump, hence have
more sustained duration of acid inhibition
• Should be taken 30minutes before meals
• PPI’s should not be given before an endoscopy as they
may mask serious underlying pathology
48

49. EXAMPLES OF PPI’S
• Omeprazole/ Esomeprazole
• Lansoprazole
• Pantoprazole
49

50. PPI’s contd
Mechanism of action:
– Inhibits the production of gastric acid by blocking
the hydrogen-potassium adenosine triphosphate
enzyme system (h+k+=atpase) of gastric parietal
cells in the gastric mucosa
– Thus the exchange of hydrogen and potassium
across the membrane to maintain gastric acidity is
inhibited
50

51. PPI’s
• Adverse effects:
– Usually mild and reversible
– Diarrheoa
– Headache
– Nausea
– Abdominal pain
– Constipation and dizziness
• Prolonged use of PPI’s is associated with
hypomagnesemia
51

52. Pharmacokinetics of PPI’s
Characteristic Omeprazole Lansoprazole Rabeprazole Pantoprazole Esomeprazole
Bioavailability(
%)
30-40 80-85 52 77 64-89
Time to peak
[plasma] (hrs)
0.5-3.5 1.7 2.0-5.0 1.1-3.1 1-2
Plasma
elimination t1/2
(hrs)
0.5-1 1.3-1.7 1.0-2.0 1.0-1.9 1.3
Protein
binding(%)
95 97 96 98 97
Urinary
excretion of
oral dose(%)
77 14-23 30-35 71-80 80

53. H2 RECEPTOR ANTAGONIST- H2RA’s
• Mechanism of action
– By blocking histamine type two receptors in
gastric parietal cells
– Thus, preventing acid secretion to reduce gastric
output
• H2 receptor antagonists in combination with
PPI at bedtime may enhance gastric PH
control at night
53

54. EXAMPLES OF H2RA’s
• Ranitidine
• Cimetidine
• Fomatidine
• Nizadine
54

55. H2RA’s
• Effectively heal ulcers when NSAID therapy is
stopped
• main role of H2RA is the empirical
management of dyspepsia symptoms
55

56. ADVERSE EFECTS OF H2RA’s
• Diarrhea
• Headache
• Dizziness
• Rash
• Tiredness
• Gynaecomastia and impotence occur occasionally
with cimetidine
56

57. Comparison of H2-receptor antagonists.
Variable Cimetidine. Ranitidine. Nizatidine. Famotidine.
Brand name Tagamet Zantac Axid Pepcid
Rel. potency 1 4-10 4-10 20-50
Dose to heal
DU(mg)
300 qid
400 bd
800 nocte
150 bd
300 nocte
150 bd
300 nocte
40 nocte
Maintenance
dose (mg)
400 nocte 150 nocte 150 nocte 20 nocte
Dose to heal
GU (mg)
300 qid
400 bd
800 nocte
150 bd N/A N/A
ABSORPTION
Bioavailability
(%)
30-80 (60) 30-88 (50) 75-100 (98) 37-45 (43)
Time to peak
[serum] (hr)
1-2 1-3 1-3 1-3.5
VOD (L/kg b.w) 0.8-1.2 1.2-1.9 1.2-1.6 1.1-1.4

58. PROSTAGLANDIN ANALOGUES
• Mechanism of action:
– Has antisecretory and protective properties
promoting peptic ulcer healing
– Can be used as prophylaxis against NSAID induced
ulcers
• Example: Misoprostol ( Cytotec)
58

59. SIDE EFFECTS
• Diarrhea (it may be severe and require withdrawal)
• Nausea &vomiting
• Dyspepsia
• Abnormal vagina bleeding with menorrhagia
• Flatulence
• Abortifaecient
59

60. SUCRALFATE
• Aluminium salt of sucrose octasulphate
• Weak antacid
• Has mucosal protective effects by stimulating
bicarbonates and mucos secretion and stimulation of
mucosal prostanoids
• Effective in the treatment of NSAID induced ulcers if
NSAID’s are stopped(2g daily)
• Main side effect is constipation
60

61. ANTACIDS
• Acts by neutralizing gastric acid
• However only effective for a short period
• Alginates are added to antacids to relieve
reflux symptoms
• Antacids are best given when symptoms occur
or are expected
61

62. ANTACIDS
• Side effects of antacid are considered in choosing type of
antacid
• Aluminium salt antacids may cause constipation
• While magnesium salts may cause diarrhea
• Hence a combination of these are preferred to produce
neutral effect on intestinal transit
• Calcium containing antacid may have an effect of
rebound acid secretion as calcium stimulates acid
secretion
– Also regular intake may cause hypercalcemia
62

63. ANTACIDS
• Antacids containing sodium bicarbonates
should not be given to patients on restricted
salt diet
• Magnesium trisilicate has very high sodium
bicarbonate content
• Liquid antacids are usually preferred over
tablets
– Antacid Dosing: 10-15mL 8 or 6 hourly; of liquid Mg-Al antacids
promote ulcer healing, but less than antisecretary drugs
63

64. ADVERSE EFFECTS OF ANTACIDS
• Constipation (Aluminium)
• Diarrhoea (Magnesium)
• Flatulence(Carbonates & bicarbonates)
• Nausea & vomiting
64

65. EXAMPLES OF ANTACIDS
• Magnesium sulfate
• Aluminium salts
• Calcium carbonate
• Sodium bicarbonate
65

66. Neutralizing capacity of some commonly used
antacid
atacid Active components Neutralising capacity (mEq)
Ducon Al(oh)3
Mg(oh)2
caco3
7.04
Maalox Al(oh)3
Mg(oh)2
2.58
Maalox plus Al(oh)3
Mg(oh)2
simethicone
2.30
Nugel AL(OH)3
Mg(OH)2
MAGNESIUM TRISILLICATE
ALGINATE
SIMETHICONE
aludrox Al(oh)3
Mg(oh)2
2.81
66

67. Management- H. pylori eradication
• Most patients with DU are infected with H. pylori
• Eradicate with 7 day course of PPI plus combination of antibiotics
classes of antibiotics used include:
– Macrolide (clarithromycin)
– Penicillin(amoxycillin)
– Metronidazole
• For initial therapy against H. pylori a 7-10 day triple therapy
comprising of a PPI or H2ra, Clarithromycin, and either amoxicillin
or metronidazole
• For a quadruple therapy, bismuth chelate is added.
• These regimen eradicate h. pylori 85% of cases
• Dual therapy of PPI and one antibiotic can be used, but produces
low rates of eradication
• PPI regimen is continued for 4-8 weeks to ensure wound healing 67

68. Amoxycillin
• Active against H. pylori
• Shown to be 90% active against H. pylori
• Should not be given to patients with true
penicillin allergy
• Erythematous rash
• Maculopapular rash
• GI adverse effects do not constitute allergy
(nausea, vomiting, diarrhoea)
• Uticarial rash does not constitue true penicillin
allergy
68

69. Clarithromycin
• Very active against h. pylori
• Generally well tolerated
• May cause GI adverse effects such as:
– Nausea
– Diarrhoea
– Vomiting
• Not given to pregnant and lactating women,
excreted in milk
69

70. Metronidazole
• Active against gram negative bacteria including h.
pylori
• Causes disulfiram-like reactions with alcohol
• Side effect:
• Metallic taste in mouth
• GI irritations including nausea and vomiting
• Metronidazole is not the first line antibiotic in h.
pylori eradication
• But it can be given when there’s treatment
failure, symptoms do not resolve.
• Tinidazole can be give in place of Metronidazole.
70

71. Current trends in management
Of peptic ulcer disease
71

72. Overview of treatment
• Give initial treatment
• Test for H. pylori
• Endoscopy and H.pylori retesting
• Stop NSAID use if possible
• Ongoing care if symptoms recur or continues
72
NICE guidelines (2015)

73. Initial treatment
– Offer H. pylori eradication therapy to people who have
tested positive for H. pylori and who have peptic ulcer
disease.
– For people using NSAIDs with diagnosed peptic ulcer, stop
the use of NSAIDs where possible.
– Offer full-dose PPI or H2RA therapy for 8 weeks and, if H.
pylori is present, subsequently offer eradication therapy.
– Offer full dose PPI or H2ra for4-8 weeks for people who
have tested negative for H. pylori and are not on NSAID’s
73

74. 74

75. ENDOSCOPY & H. PYLORI RETESTING
• Repeat endoscopy and H. pylori retesting for
patient 6-8 weeks after treatment
• This depends on the size of the lesion
• Carbon 14 breath test may be insufficient at
this stage
75

76. NSAID USE
• Discuss potential of nsaid treatment for people
who have to take NSAID’s after the ulcer is healed
• Review the need for NSAID use regularly, at least
every 6 months
• Consider dose reduction or substituting with
paracetamol
• Or use an alternative or low dose ibuprofen
• If NSAID continuation is very necessary, consider
cox 2 selective NSAIDs
76

77. UHEALED ULCER/ CONTINUED SYMPTOMS/
RECURRENCE
• In people with an unhealed ulcer, rule out
– non-adherence,
– malignancy,
– failure to detect H. pylori,
– inadvertent NSAID use or other ulcer-inducing medication
– and rare causes such as Zollinger–Ellison syndrome or
Crohn's disease.
• If symptoms recur after initial treatment, offer a PPI to
be taken at the lowest dose possible to control
symptoms.
• Discuss using the treatment on an 'as-needed'
basis with people to manage their own symptoms.
77

78. Current drug regimen- H. pylori eradication
PPI ANTIBIOTIC
amoxicillin clarithromycin metronidazole
Esomeprazole
20mg 12hrly
1g 12hrly 500mg 12hrly ------------
----------- 500mg 12hrly 400mg 12hrly
Omeprazole
20mg 12hrly
1g 12hrly 500mg 12hrly ------------
500mg 8hrly -------------- 400mg 8hrly
-------- 500mg 12hrly 400mg 12hrly
Rabeprazole
20mg 12hrly
1g 12hrly 500mg 12hrly
---------
----------- 500mg 12hrly 400mg 12hrly
78

79. CURRENT DRUG REGIMEN- NSAID INDUCED
ULCERS
• Esomeprazole, oral:
– Adults:-20 mg daily for 4 weeks. Repeat course if
ulcer is not fully healed.
• Or Omeprazole, oral,
– Adults:20 mg daily for 4 weeks. Repeat course if
ulcer is not fully healed.
• Or Rabeprazole, oral,
– Adults:20 mg daily for 4 weeks. Repeat course if
ulcer is not fully healed.
79

80. CURRENT DRUG REGIMEN- BLEEDING PEPTIC
ULCER
• · Esomeprazole, IV,
– Adults:40 mg daily
• Or Omeprazole, IV,
– Adults:40 mg 12 hourly for up to 5 days
80

81. PATIENT EDUCATION
• Seek pharmacist advice when purchasing OTC analgesics
• Patients with risk of peptic ulceration should be advised to avoid otc
aspirin and NSAIDs
• Taking aspirin and NSAIDs with or after food may decrease risk of
dyspepsia
• Patient should be aware of optimum time for administration of PPI,
dose duration therapy
• Misoprostol should not be used in pregnant women and women of
child bearing age
• Patients need to know the importance of adherence to eradication
therapy for successful treatment, to prevent resistance
81

82. ROLE OF THE PHARMACIST…
• Pharmaceutical care for peptic ulcer patients
– Monitoring treatment
– Efficacy of treatment: (the signs and symptoms and
investigations are looked)
– the toxicity of the medicines: (relies on harmful side effects).
– Counselling
• if patients are adequately counselled on their disease, aims of
therapy, life style modification and advice on managing side effects
effective concordance can be obtained.
82

83. ROLE OF THE PHARMACIST
• General public (patient) Education and Counseling on;
– Potentially harmful agents, including:
• NSAIDs
• Aspirin
• Alcohol
• Tobacco
• Caffeine
– Stress Reduction
83

84. CONCLUSION
• An understanding of how peptic ulcer occurs, in
concept with a good knowledge of potent acid
suppressing drugs as well as the implication of H.
pylori in PUDs have changed the face of ulcer
therapy providing hope for better prognosis over
time.
84

85. REFERENCES
• Annual Report,2013, Korle Bu Teaching Hospital, pp
22,111-112
• British National Formulary (BNF) 68th edition
• Hatakeyama, M et al (2014). H.pylori cagA and gastric
cancer: a paradigm for hit and run carcinogenesis
• Etc……
85

86. THANK YOU
86