2. New Perspectives in The Management of Peptic
Ulcer Disease.
Professor Javed Akram.
Mb, MEE(Can), MRCP(UK), FRCP(Glasg), FRCP(Edin), FRCP(London),
FACP(USA), FASIM(USA), FACC(USA).
3. Peptic Ulcer Disease
A peptic ulcer is a break (an ulceration) in
the protective mucous lining (mucosa) of
the lower esophagus, stomach or duodenum
4. Common Misconceptions
A peptic ulcer is NOT:
A stress ulcer
Chronic gastritis (a symptom as well as a disease state
that may lead to peptic ulcers)
Dyspepsia (the symptoms that may or may not be
diagnosed as an ulcer)
Peptic Ulcers cannot be diagnosed solely on the
basis of clinical presentation (Werdmuller et al.
1996)
6. Dyspepsia - Definition
A group of symptoms which alert
clinicians to consider disease of the upper
gastrointestinal tract
(British Society of Gastroenterology, 1996)(British Society of Gastroenterology, 1996)
7. Symptoms of Functional Dyspepsia
NocturnalNocturnal
painpain
LocalizedLocalized
epigastricepigastric
burningburning
BetterBetter
with foodwith food
HeartburnHeartburn
RetrosternalRetrosternal
burningburning
NauseaNausea
BloatingBloating
Early satietyEarly satiety
WorseWorse
with foodwith food
Ulcer-like DominantUlcer-like Dominant Dysmotility-like DominantDysmotility-like Dominant
8. Quick Stats:Peptic Ulcer
5-10% lifetime incidence
1-2% of people have ulcer at any given time
$5.65 billion industry
10. Types
Gastric
Slightly more common in men and way more
common in elderly
Most commonly located in the stomach’s lesser
curvature, antrum
1-3% associated with gastric carcinomas
Basic defect is disruption of gastric mucosal
barrier (gastritis, duodenal reflux, H. pylori,
NSAIDS)
11. Types
Duodenal
Almost always located in the duodenal bulb
More likely culprit in chronic disease
No association with cancer
12.
13.
14. Risk Factors
Smoking
33-100% more likely to develop duodenal ulcers
Retards healing of identified ulcers
J Akram& Colleagues ..E.J.of Gastrenterology.Nov2003)
Age and Sex
Alcohol
Diet
Milk
Stress
Ramadan fasting
15. Risk Factors
NSAIDS
Responsible for majority of ulcers not caused
by H.pylori
Greater risk for complications once ulcer
identified
Risk of GU increases sixfold when taking
>three aspirin/day. Buffered coat has no
advantage
16. Prevalence of Endoscopic
NSAID-Induced Ulceration
Mean Range
Gastric Ulcer 15 % 10 to 30%
Duodenal Ulcer 5 % 4 to 10 %
Clinically Significant Ulcers 2% 1 to 4%
17. Risk Factors for
Serious GI Adverse Events with NSAIDs: Relative Risks
Rodriguez. Lancet. 1994; Guttham. Epidemiology. 1997; Shorr. Arch Intern Med.
1993; Piper. Ann Intern Med. 1991.
0 5 10 15
4.4 (2.0-9.7)
12.7 (6.3-25.7)
2.9 (2.2-3.8)
5.8 (4.0-8.6)
5.6 (4.6-6.9)
3.1 (2.5-3.7)
1.6 (1.4-2.0)
13.5 (10.3-17.7)
Corticosteroid use
Anticoagulant use
Low dose NSAIDLow dose NSAID
High dose NSAID
Age 70-80
Age 60-69
Age 50-59
Prior bleed
Relative RiskRelative Risk
19. Peptic Ulcers and Stress
Experimental stress results in decreased
upper gastrointestinal blood flow in animals
(Kauffman, 1997; Livingston 1993)
Effect of stress seems to be reversible
(Levenstein et al., 1996)
20. Peptic Ulcer and Personality
Studies have found a strong association
between dependency and peptic ulcers
Patients with peptic ulcer have significantly
more personality disturbances than control
subjects (Feldman et al.)
Ulcer patients also more inclined to
pessimism and excessive dependence
(Akram et al.)
21.
22. Helicobacter pylori
Gram-negative spiral organism
Most common and important risk factor for
duodenal ulcer
Variable risk factor for gastric ulcers
10% healthy people under 30, 60% healthy
people over 60.
Will cause disease in 15-20% of infected
Eradication is the key
24. Diagnosis
Vague discomfort and feeling of gnawing hunger
Duodenal usually has predictable food relationship (1-3 hrs after meal)
Gastric ulcer relationship with food more variable
Gastric ulcer-weight loss
Duodenal ulcer-weight gain
Watch for peptic ulceration/bleeding: melena, radiation of pain to
back/shoulder
26. Studies
Radiography
Barium swallow with double contrast
Duodenal-detects 40-80%
Gastric-detects 65-80%
Endoscopy
Gold standard
Detects up to 95% gastroduodenal ulcers
Generally considered the study of choice esp. for
large ulcers or those not clearly benign
27. Diagnosis of H. pylori
Invasive (if patient requires endoscopy)
Histologic testing (50-90% sensitive, 100%
specific)
Rapid urease (CLO) test (95% sensitive and
95% specific)*
Noninvasive
IgG antibody*
Urea breath test (96% sensitive, 98% specific)
30. A common medical condition
250,000 – 500,000 admissions/year in US
UGI bleeding incidence 100/100,000 adults
Incidence increases 20-30 fold from third to
ninth decade of life
GI bleeding stops spontaneously in 80 %
32. Therapy
Goal is to heal the ulcer and prevent
recurrence
Both can be accomplished by eradicating H.
pylori if present
Treat the acute pain if necessary
33. Nonpharmacologic
There is no evidence that dietary modifications
changes the course of the disease
Quit smoking
Milk intake
Faster healing, lower recurrence, lower
complications
Discontinue NSAIDS
COX2 Inhibitors?
34. Treatment of ulcers
Eradicate H. pylori
Single antibiotic therapy does not work
Compliance is key
More than 60% of the doses must be taken to ensure
eradication
If eradicated, maintenance therapy not needed. If
recurs, check for H. pylori again
If H. pylori not found, check again and treat with H2-
receptor antagonists, PPI’s and sucralfate
Document healing of gastric ulcers with endoscopy
38. PHAMACOKINETICSPHAMACOKINETICS
ABS0RPTION
Minimal absorption by GIT 3-5%
ABS0RPTION
Minimal absorption by GIT 3-5%
EXCRETION
Approximately 90% is excreted in the stool, very
small amount is excreted in the urine.
EXCRETION
Approximately 90% is excreted in the stool, very
small amount is excreted in the urine.
39. INDICATIONS OF ULCOCID
Duodenal ulcers
Gastric ulcers
treatment of reflux and peptic oesophagitis
H.pylori
treatment of NSAID & aspirin induced GI symptoms and
mucosal damage.
Prevention of stress ulcers and GI bleeding in critically ill
patients.
Treatment of oral and oesophageal ulcers due to radiation
chemotherapy & sclerotherapy.
Sucralfate enemas in ulcerative colitis & colonic
carcinomas
Duodenal ulcers
Gastric ulcers
treatment of reflux and peptic oesophagitis
H.pylori
treatment of NSAID & aspirin induced GI symptoms and
mucosal damage.
Prevention of stress ulcers and GI bleeding in critically ill
patients.
Treatment of oral and oesophageal ulcers due to radiation
chemotherapy & sclerotherapy.
Sucralfate enemas in ulcerative colitis & colonic
carcinomas
40. AVAILABILITY OF DRUG
1. ULCOCID tablets
( containing 500 mg Sucralfate per tablet ).
2. ULCOCID tablets
( containing 1 g Sucralfate per tablet ).
3. ULCOCID Susp. 60 ml
( containing 1 g Sucralfate per 5ml).
1. ULCOCID tablets
( containing 500 mg Sucralfate per tablet ).
2. ULCOCID tablets
( containing 1 g Sucralfate per tablet ).
3. ULCOCID Susp. 60 ml
( containing 1 g Sucralfate per 5ml).
41. DOSAGE RECOMMENDATION OF ULCOCID
For Ulcer Patients
Morning
2g Ulcocid
Evening
For Non Ulcer Patients
Morning
1 g Ulcocid
Evening
For Ulcer Patients
Morning
2g Ulcocid
Evening
For Non Ulcer Patients
Morning
1 g Ulcocid
Evening
42. ULCOCID
ULCOCID should always be
taken 1 hour before meals at
bed time (Monotherapy)
Do not take antacids 1/2 hour
before or after taking
ULCOCID (Polytherapy).
ULCOCID should always be
taken 1 hour before meals at
bed time (Monotherapy)
Do not take antacids 1/2 hour
before or after taking
ULCOCID (Polytherapy).
43. ANTACIDS Vs ULCOCD
ANTACIDS
Just symptomatic therapy.
Intense antacid regimen required
for healing.
Not safe for hypertensive or
cardiac patients.
Non-Palatable.
Not suitable for working class
because of frequent dose taken.
ANTACIDS
Just symptomatic therapy.
Intense antacid regimen required
for healing.
Not safe for hypertensive or
cardiac patients.
Non-Palatable.
Not suitable for working class
because of frequent dose taken.
ULCOCID
Ulcer healing occurs.
None
Palatable
Dosage is convenient.
ULCOCID
Ulcer healing occurs.
None
Palatable
Dosage is convenient.
44. Ulcocid Vs H2- Receptor AntagonistsUlcocid Vs H2- Receptor Antagonists
Ulcocid
Less side effects
Can be administered to elderly.
Smokers can use it.
Does not effect hepatic
metabolism of drugs.
Does not effect pulmonary
functions in patients with pre-
existing broncho- pulmonary
diseases.
Ulcocid
Less side effects
Can be administered to elderly.
Smokers can use it.
Does not effect hepatic
metabolism of drugs.
Does not effect pulmonary
functions in patients with pre-
existing broncho- pulmonary
diseases.
H2-Receptor Antagonists
More side effects
Causes hallucination and delirium
in elderly
Only for non- smokers.
Does effect the metabolism of
drugs metabolized by Cytochrome
P-450 path-way.
H2 – blockers may worsen the
condition.
H2-Receptor Antagonists
More side effects
Causes hallucination and delirium
in elderly
Only for non- smokers.
Does effect the metabolism of
drugs metabolized by Cytochrome
P-450 path-way.
H2 – blockers may worsen the
condition.
45. Human Studies.Human Studies.
Comparative evaluation of Sucralfate &
Cimetidine efficacy in treatment of chronic
erosive gastritis.
The results of patients with chronic erosive
gastritis treated with Sucralfate &
Cimetidine were compared. The result of
examinations indicate that chronic erosive
gastritis is difficult to be heal; Sucralfate
proved to be more efficient than
Cimetidine.
Ref: Au:Kula-Z:Walasek-L So:Pizegl-Lek 1998; 51(2): 73-6
Comparative evaluation of Sucralfate &
Cimetidine efficacy in treatment of chronic
erosive gastritis.
The results of patients with chronic erosive
gastritis treated with Sucralfate &
Cimetidine were compared. The result of
examinations indicate that chronic erosive
gastritis is difficult to be heal; Sucralfate
proved to be more efficient than
Cimetidine.
Ref: Au:Kula-Z:Walasek-L So:Pizegl-Lek 1998; 51(2): 73-6
46. Meta-analysis:Human Studies.Meta-analysis:Human Studies.
Comparative evaluation of Sucralfate &
Cimetidine efficiency in treatment of
chronic erosive gastritis proved that
Sucralfate is more efficient than
Cimetidine.
Ref: Au: Kula-Z:Walasek-L So:Pizegl-Lek 1999; 51(2): 73-6
Comparative evaluation of Sucralfate &
Cimetidine efficiency in treatment of
chronic erosive gastritis proved that
Sucralfate is more efficient than
Cimetidine.
Ref: Au: Kula-Z:Walasek-L So:Pizegl-Lek 1999; 51(2): 73-6
47. ULCOCID Vs ACID PUMP
INHIBITORS
ULCOCID Vs ACID PUMP
INHIBITORS
Acid Pump Inhibitors
Jaundice has been reported.
Hypoglycaemia, Wt. Gain.
Increased intragastric
concentrations of viable
bacteria during the T/M.
Acid Pump Inhibitors
Jaundice has been reported.
Hypoglycaemia, Wt. Gain.
Increased intragastric
concentrations of viable
bacteria during the T/M.
Ulcocid
No jaundice reported
None
None
Ulcocid
No jaundice reported
None
None
48. Anti Helicobacter effects
Omeprazole Vs Ulcocid
(With Clarithromycin and Metronidazole)
75
80
85
90
95
100
4 Weeks
Healing
H.Pylori
eradication
Omeprazole
Ulcocid
50. HUMAN AND ANIMAL STUDIES
Invitro and clinical data suggest that triple
therapy with SUCRALFATE is effective in
eradicating HELICOBACTER PYLORI and
reducing duodenal ulcer relapse.
Ref: Louw- Ja So:Scand-J-Gastroenterol-Suppl. 1998; 191:28-31
Invitro and clinical data suggest that triple
therapy with SUCRALFATE is effective in
eradicating HELICOBACTER PYLORI and
reducing duodenal ulcer relapse.
Ref: Louw- Ja So:Scand-J-Gastroenterol-Suppl. 1998; 191:28-31
51. Human StudiesHuman Studies
Glycosulfatase activity of H. Pylori towards human
gastric mucin; effect of Sucrafate.
Results demonstrate that H. Pylori, through its Glycosulfatase
activity affects the sulphated mucin & glycero-gluco-lipid
content of the protective mucous layer & that anti-ulcer
drug Sucralfate is able to counteract the detrimental action
of this enzyme.
Ref: Slomiany-BL; Piotrowski-J; Grabska-M; SLOMIANY-a So: Am-j-
Gastroenterol. 1999 Sep; 87(9); 1132-7
Glycosulfatase activity of H. Pylori towards human
gastric mucin; effect of Sucrafate.
Results demonstrate that H. Pylori, through its Glycosulfatase
activity affects the sulphated mucin & glycero-gluco-lipid
content of the protective mucous layer & that anti-ulcer
drug Sucralfate is able to counteract the detrimental action
of this enzyme.
Ref: Slomiany-BL; Piotrowski-J; Grabska-M; SLOMIANY-a So: Am-j-
Gastroenterol. 1999 Sep; 87(9); 1132-7
52. ULCOCID INHIBITS THE EFFECT OF
H.Pylori on gastric mucins
ULCOCID INHIBITS THE EFFECT OF
H.Pylori on gastric mucins
0
200
400
600
800
1000
1200
Specific binding (dpm/assay)
Control 10 40 80
ULCOCID (mg/ml)
53. ULCOCID
Direct binding to ulcer
crater
Stimulates prostaglandin
production
Enhances the surface
active phospholipid
mucosal barrier.
Stimulates growth factors
. Epidermal
. Transforming
. Fibroblast
Anti-helicobacter effects.
58. HUMAN STUDIESHUMAN STUDIES
Management of bleeding in a patient with
colorectal cancer:
SUCRALFATE an oral cytoprotective, used
topically in a patient with colo-rectal cancer
resulting in control of bleeding, less
localized pain and more freedom &
independence for the patient.
Ref: Au: Famcombe-M So: Support-care-cancer, 1993 May;1(3):159-60.
Management of bleeding in a patient with
colorectal cancer:
SUCRALFATE an oral cytoprotective, used
topically in a patient with colo-rectal cancer
resulting in control of bleeding, less
localized pain and more freedom &
independence for the patient.
Ref: Au: Famcombe-M So: Support-care-cancer, 1993 May;1(3):159-60.
59. WHY ULCOCID ?WHY ULCOCID ?
Fast pain relief.
Excellent healing rate.
Equal good for smokers and non - smokers.
Good for elderly.
Equally good for ulcer and non - ulcer
patients.
Economical
Fast pain relief.
Excellent healing rate.
Equal good for smokers and non - smokers.
Good for elderly.
Equally good for ulcer and non - ulcer
patients.
Economical