APD Presentation by Prof.Javed akram

APD

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)

5. Dyspepsia.

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
Nocturnal Nocturnal
pain pain
Localized Localized
epigastric epigastric
burning burning
BetterBetter
with food with food
HeartburnHeartburn
RetrosternalRetrosternal
burningburning
NauseaNausea
BloatingBloating
Early satietyEarly satiety
WorseWorse
with food with food
Ulcer-like DominantUlcer-like Dominant Dysmotility-like Dominant Dysmotility-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

9. Peptic Ulcer Hospitalization RatesPeptic Ulcer Hospitalization Rates
Kurata JH. Kurata JH. Semin Gastrointest DisSemin Gastrointest Dis 1993:4 1993:4
RateRate
per per
100,000100,000
Gastric UlcerGastric Ulcer Duodenal UlcerDuodenal Ulcer
70 75 80 85 90
0
20
40
60
80
100
Uncomplicated Uncomplicated
HemorrhageHemorrhage

Perforation Perforation
70 75 80 85 90
0
20
40
YearYear YearYear
30
10
Uncomplicated Uncomplicated
HemorrhageHemorrhage
Perforation Perforation

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

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
MeanRange
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

18. NSAID
↑ Leukocyte-Endothelial
Interactions
Capillary
Obstruction
Ischemic
Cell Injury
Proteases +
Oxygen Radicals
Endo/Epithelial
Cell Injury
Mucosal Ulceration
L
o
s s o
f P
G
E
2
a
n
d
P
G
I 2
m
e d
i a
t e d
i n
h
i b
i t i o
n
o
f a
c i d
s e c r e t i o
n
a
n
d
c y
t o
p
r o
t e c t i v
e e f f e c t
Loss of PGI
2
induced inhibition of LTB
4
mediated
endothelial adhesion and activation of neutrophils

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.)

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

23. Diagnosis of Peptic Ulcer

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

25. Physical Exam
Epigastric tenderness
Rectal exam!!

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)

28. Complications
Perforation
Reoccurrence
Obstruction
Bleeding
Cancer

29. Upper GI Bleeding

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 %

31. Bleeding Stats:Mayo J.Akram etal 2001PJGE

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

35. ULCOCID
(Sucralfate)

36. Chemical Structure of Sucralfate p
p c,dfMvep5dtiv,N)uite ppppppp AMNhpiN,UPr,Up:hwfMIPwe
ppp pppppp c,dfiNyite
pppp Q .l p: 2 p5 .. pRc5 J pmN l px5:H & Eprp: l p5

Sucrose Octasulphate Poly aluminum Hydroxide
Sucralfate
C12 H6 O11 [SO3 Al2 (OH)5] n H2 O

37. ULCOCID
(Sucralfate).gppWMrpvhvteUPd
lgppQhtM)fMtedtPCe
JgppmdPwppfeNitewpwPvMfwefv
1. Non systemic
2. Cytoprotective
3. Acid related disorders

38. A:mTmQ5jFWk(FQc
PHAMACOKINETICSm cD>A(F5W

TPrPUiNpiOvMf)tPMrpOhpbF(pJG&$
ABS0RPTION
Minimal absorption by GIT 3-5%k0Q>k(F5W

m))fMIPUiteNhp/D$pPvpeIdfetewpPrptuepvtMMN6pCefh
p vUiNNpiUM,rtpPvpeIdfetewpPrptuep,fPreg
EXCRETION
Approximately 90% is excreted in the stool, very
small amount is excreted in the urine.

39. INDICATIONS OF ULCOCID
S,MweriNp,Ndefv

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difdPrMUiv
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.g 3BQ5QFS ptiONetvp
xpdMrtiPrPrsp&DDpUspc,dfiNyitep)efptiONetpHg
lg 3BQ5QFS ptiONetvp
xpdMrtiPrPrsp.pspc,dfiNyitep)efptiONetpHg
Jg 3BQ5QFS ppc,v)gp2DpUN
p xpdMrtiPrPrsp.pspc,dfiNyitep)efp&UNHgp
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 ULCOCID9Mfp3NdefpAitPertv
ppppppppppppppppppppppppppppppppppppppppp TMfrPrs
ppppppppp lsp3NdMdPw
ppppppppppppppppppppppppppppppppppppppppp kCerPrs
pppppppppppppp 9MfpWMrp3NdefpAitPertv
ppppppppppppppppppppppppppppppppppppppppp TMfrPrs
ppppppppp .psp3NdMdPw
ppppppppppppppppppppppppppppppppppppppppp kCerPrs
For Ulcer Patients
Morning
2g Ulcocid
Evening
For Non Ulcer Patients
Morning
1 g Ulcocid
Evening

42. ULCOCID3BQ5QFS pvuM,NwpiN-ihvpOep
tioerp.puM,fpOeyMfepUeiNvpitp
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OeyMfepMfpiytefptioPrsp
3BQ5QFSp xAMNhtuefi)hH g
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 Ne wPrs

a,vtpvhU)tMUitPdptuefi)hg

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yMfpueiNPrsg

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difwPidp)itPertvg

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Oedi,vepMypyfeE,ertpwMveptioerg
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.pcwtwPr

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ULCOCID
Ulcer healing occurs.
None
Palatable
Dosage is convenient.

44. pivnvThMMagMMmofMUlvlD.nAM b.k(nbTg.g
Ulcocid Vs H2- Receptor AntagonistspivnvTh

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eIPvtPrspOfMrduMGp),NUMrifhp
wPveivevg
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.mofUlvlD.nAM b.k(nbTg.g

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dMrwPtPMrg
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. :,Uirpct,wPevg
Human Studies.QMU)ifitPCepeCiN,itPMrpMypc,dfiNyitepAp
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>eynpm,nj,NiGJnKiNiveoGBpcMnAPFesNGBeop.//LIp&.xlHnpMJG2
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. NewPwrwspctcivnTwrhMenatNcg
Meta-analysis:Human Studies.hh moTfwUwetlNhNlwsnwetorhoDhMn.UwsDweNhAh
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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. %Om2m$Ghh’chhum$Gh:% :h
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ULCOCID Vs ACID PUMP
INHIBITORS NewPrspcPtiveneThMa

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Acid Pump Inhibitors
Jaundice has been reported.
Hypoglycaemia, Wt. Gain.
Increased intragastric
concentrations of viable
bacteria during the T/M.gmNhNew

3ohEwnrat.NhUNfoUeNah

3orN

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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

49. Ulcocid Counters the Effect of
H.Pylori on Gastric Mucosavg:>O2($
? P n.nchltc.octep
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? P 3w/&v/hNA.bwrkNhoDhTn.nc
? P n.ocwshIt.wUIorweNhcN.UNetor
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fNUTNwItsteph
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? h MnUDw.NhbpaUofboIt.tep
? h mNsshTNTIUwrNhfNUTNwItstep
? h v/hBw.ChatDDnctorg
H.PYLORI
¯ Mucus viscosity
¯ Glycoproteins & lipids
¯ Na+/H+ exchange of mucus
¯ Mucosal bicarbonate secretion
¯ Cell desquamation
¯ Mucosal microvessel
permeability
¯ Mucosal blood flow?
¯ Surface hydrophobicity
¯ Cell membrane permeability
­ H+ Back diffusion.%Om2m$G
? P n.nchltc.octep
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? h n.ocwsh:JjSRh n.ocwsh
UNrNCws
? h n.ocwshIsooahDsoC
? h MnUDw.NhbpaUofboIt.tep
? h mNsshTNTIUwrNhfNUTNwItstep
? h v/hBw.ChatDDnctorg
ULCOCID
­ Mucus viscosity
­ Glycoproteins & lipids
­ Na+/H+ exchange of mucus
­ Mucosal bicarbonate secretion
­ Mucosal PGE2, Mucosal
renewal
­ Mucosal blood flow
­ Surface hydrophobicity
­ Cell membrane permeability
¯ H+ Back diffusion.

50. HUMAN AND ANIMAL STUDIEShhh $rlteUohwrah.strt.wshawewhcnkkNcehebweheUtfsNh
ebNUwfphCtebhM%m(uOEuxjhtchNDDN.etlNhtrh
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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. vnTwrhMenatNc
Human StudiesJsp.ocnsDwewcNhw.etltephoDhvgh:psoUtheoCwUachbnTwrh
kwceUt.hTn.tr9hNDDN.ehoDhMn.UwDweNg
(NcnsechaNTorceUweNhebwehvgh:psoUtRhebUonkbhtechJsp.ocnsDwewcNh
w.etltephwDDN.echebNhcnsfbweNahTn.trhAhksp.NUoPksn.oPstftah
.oreNrehoDhebNhfUoeN.etlNhTn.onchswpNUhAhebwehwretPns.NUh
aUnkhMn.UwsDweNhtchwIsNheoh.onreNUw.ehebNhaNeUtTNrewshw.etorh
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JwceUoNreNUosghW111hMNf9hFQ-1F9hWW5SPQ
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. %Om2m$Gh$3v$B$xMhxvjhjEEjmxh2Eh
vg:psoUthorhkwceUt.hTn.trc
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.

54. Recurrent Aphthous Stomatitis (RAS)
Minor apthae

55. Recurrent Aphthous Stomatitis (RAS)
Major apthae

56. Sucralfate in apthous ulcers.
F.Khan,A.Awan,J.Akram SMJ,Jun,2003
Statistically significantly better pain relief
Earlier ulcer healing rates
Better QOL

57. Sucralfate Enema
Ulcerative Colitis
Ca.Colon

58. v% u3hMx%G$jMh
HUMAN STUDIES wrwkNTNrehoDhIsNNatrkhtrhwhfwetNrehCtebh
.osoUN.ewsh.wr.NUi
M%m(uOEuxj hwrhoUwsh.peofUoeN.etlNRhncNah
eoft.wssphtrhwhfwetNrehCtebh.osoPUN.ewsh.wr.NUh
UNcnsetrkhtrh.oreUoshoDhIsNNatrkRhsNcch
so.wstyNahfwtrhwrahToUNhDUNNaoThAh
traNfNraNr.NhDoUhebNhfwetNreg
(NDihunihEwT.oTINP hMoihMnffoUeP.wUNP.wr.NURhW115h wp 9W-5FiW61P0Gg
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. dv>hhh%Om2m$GhD
WHY ULCOCID ?
EwcehfwtrhUNstNDg

jA.NssNrehbNwstrkhUweNg

jBnwshkooahDoUhcToCNUchwrahrorhPhcToCNUcg

JooahDoUhNsaNUspg

jBnwssphkooahDoUhns.NUhwrahrorhPhns.NUh
fwetNrecg

j.oroTt.ws
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

60. Thank You.