Transcript PEPTIC ULCER AND NON ULCER DYSPEPSIA

PEPTIC ULCER AND NON ULCER
DYSPEPSIA
DR BANU NISA ABDUL HAMID
MASTER IN FAMILY MEDICINE
1ST YEAR POSTGRADUATE , UKM
Objective
• most likely causes of dyspepsia
• risk factors of recurrent peptic ulcer disease
• role of Helicobacter pylori in the pathogenesis of
peptic ulcer
• disease and its relationship to ulcer relapses
• manage patients presented with dyspepsia
• role of available drugs for the treatment of dyspepsia
• recognise the indications for long-term maintenance
therapy
• manage patients with PUD and concomitant high CVD
risk needing antiplatelet therapy
DYSPEPSIA
• Defination:
- having one or more symptoms of epigastric
pain, burning, post-prandial fullness, or early
satiation.
5 MAJOR CAUSE
a) Gastro-esophageal reflux (GERD)
b) Medications
c) Functional dyspepsia (FD) – non ulcer
dyspepsia
d) Peptic ulcer disease (PUD)
e) Malignancy
Some medications that commonly
cause dyspepsia
•
•
•
•
•
•
•
NSAIDS
Cox-2 inhibitors
Bisphosphonates
Erythromycin
Tetracyclines
Iron
Potassium supplements
•
•
•
•
•
Acarbose
Digitalis
Theophylline
Orlistat
Aspirin
FUNCTIONAL DYSPEPSIA
FUNCTIONAL DYSPEPSIA
• Rome III working group defined FD
presence of symptoms thought to originate in
gastro-duodenal region, in the absence of any
organic, systemic ,or metabolic disease that is
likely to explain them.[Tack et al. 2006].
FUNCTIONAL DYSPEPSIA
• Non ulcer dyspepsia
FD
FD
(subgroups)
• Irritable bowel
syndrome
• Post prandial distress
syndrome (PDS)
• Epigastric pain
syndrome (EPS)
Rome III diagnostic criteria for
functional dyspepsia
At least 3 months of one or more of the
following:
• bothersome postprandial fullness
• early satiation
• epigastric pain
• epigastric burning
AND
• no evidence of structural disease (including upper
endoscopy) that is likely to explain the symptoms.
Pathophysiological mechanism
• Delayed gastric emptying
• Impaired gastric accommodation to a meal
• hypersensitivity to gastric distention
• H. pylori infection
• altered duodenal response to lipids or acid
• abnormal duodenojejunal motility
• central nervous system dysfunction
[Tack et al. 2004].
Pathophysiologic mechanisms in functional
dyspepsia. H+, acid exposure.
CNS modulation  stress,illness
Visceral hypersensitivity (fat,
,wall distension)
Vagal neuropathy
Inflammation gastric contents
[bacteria (H. pylori), viruses, etc.]
Acid hypersensitivity
Decrease fundic
accommodation
Abnormal distribution of
Igastric contents
Gastric dysarrhytmias
Delayed gastric emaptying/
Antral hypomotility
Overdistended antrum
Duodenal hypersensitivity
Small bowel dysmotility
Diagnostic criteria: PDS
1. Bothersome postprandial fullness, occurring
after ordinary sized meals, at least several
times per week AND/OR
2. Early satiation that prevents finishing a
regular meal
Supportive criteria
1. Upper abdominal bloating, postprandial
nausea or excessive belching can be present
2. Epigastric Pain Syndrome may coexist
Diagnostic criteria: EPS
1. Pain or burning localized to the epigastrium
of at least moderate severity at least once per
week AND
2. The pain is intermittent AND
3. Not generalized or localized to other
abdominal or chest regions AND
4. Not relieved by defecation or passage of
flatus AND
5. Not fulfilling criteria for gallbladder and
sphincter of Oddi
Diagnostic criteria: EPS
Supportive criteria
1. Upper abdominal bloating, postprandial
nausea or excessive belching can be present
2. The pain is commonly induced or relieved by
ingestion of a meal but may occur while
fasting
3. Postprandial distress syndrome may coexist
Management of
functional dyspepsia.
PPI
FD
H.pylori
eradiacation
Promotility
agents
Nonresponders
Alternative
therapies
Tricyclics
SSRI
Promotility
agents
PEPTIC ULCER DISEASE
PEPTIC ULCER
• Defination:
mucosal lesions that penetrate the muscularis
mucosae layer and form a cavity surrounded
by acute and chronic inflammation.
Two types:
Gastric
ulcer
Duodenal
ulcer
• Located in the
stomach often along
the lesser curvature
• Located in the
duodenal bulb.
In Malaysia
• Few reports on the pattern of peptic ulcer in
Malaysia.
• Male are more prone than female
• In both sexes, GU –older age grp compare to
DU
• Of the 3 main Malaysian ethnic grp, Chinese
of both sexes had the highest frequency of
peptic ulcer.
• Chinese female had the highest frequency of
DU.
(Source: Profile of PUD in Malaysia,M V Kudva)
Prevalence of PUD reached a peak early in 20th
century but decreased during more recent
decades.
Widespread use of ASA & NSAIDS esp in older
patients and those with comorbidities.
The decreasing prevalance both from the
reduction of patient with recurrent ulcer treated
for H.pylori AND from the decreasing prevalence
of H.pylori infection in the population.
Risk factor
• Major risk factor:
Helicobacter pylori infection
NSAIDS
ASA
Etiology and risk factors for peptic ulcer
disease
Odds Ratio
Nonsteroidal anti-inflammatory drugs
3.7
Helicobacter pylori
3.3
Chronic obstructive pulmonary disease
Chronic renal insufficiency
2.34
2.29
Current tobacco use
1.99
3 or more doctor visits in a year
1.49
Coronary heart disease
1.46
Former alcohol use
1.29
obesity
1.18
Clinical Manifestation
• Night time awakening /episodic epigastric pain
relieved following food intake (most specific
clinical sign)
• Epigastric pain describe as episodic , dull,
burning (dyspepsia) pain.
• 46% of patients had reflux symp (heartburn,
acid regurgitation) ~ GERD
Clinical manifestation
DU
GU
• Awakening at night
between 12 to 3am
• Pain improves with
food intake
• Weight loss
precipitated by fear
of food intake
Clinical manifestation
• Most common symp of
PUD (> 80 yo) :
1) Epigastric pain (74%)
2) Nausea (23%)
3) Vomiting ( 20%)
•
-
Less common features:
Indigestion
Belching
Vomiting
Associated with
gastric/pyloric stenosis
- LOA
- Intolerance to fatty
foods
- Positive FHX
Definitive diagnosis
• direct visualization of the ulcer via
radiography (upper GI barium swallow, double
contrast) or upper GI endoscopy (EGD).
• Referral to EGD should be considered in all
patients:
50 years of age or older, with persistent
symptoms, anorexia, weight loss, vomiting,
 and in the presence of signs of GI bleeding.
Differential diagnosis of peptic ulcer disease
CONDITION
TEST(s)
FINDINGS
Gastritis
Upper gastrointestinal
endoscopy
Gastric inflammation
Gastroesophageal
reflux disease
Symptoms
Dyspepsia worse with eating
and upon lying down
Gastroparesis
History
History of diabetes
Cholelithiasis
Examination
Abdominal ultrasound
Right upper quadrant
tenderness
Gallstones
Pancreatitis
Amylase/lipase
Elevated
Gastric cancer
Upper gastrointestinal
endoscopy
Abdominal CT scan
Biopsy
Abdominal aortic
aneurysm
Abdominal ultrasound
Abdominal CT scan
Size of aorta
Hepatitis
Liver function tests
Elevated
Condition
Test(s)
Findings
Myocardial ischemia
Cardiac enzymes
Electrocardiogram
Elevated CPKMB
Elevated troponin
ST segment changes
Deep symmetric T wave
inversion
Mesenteric ischemia
Symptoms
Abdominal CT
Pain after meals
Mesenteric edema; bowel
dilatation; bowel wall
thickening; intramural
gas; mesenteric stranding
Common Complication
GI bleeding
Perforation
Gastric outlet
obstruction
GI Bleeding
• 80 % stop
spontaneously- only
supportive Rx required
• Asymptomatic/hematemesis,coffee ground
emesis,malena,
tachycardia,shock.
• Urgent OGDS –detect
cause of bleeding, start
on appropriate therapy.
• Shock presentaggressive resuscitation
& blood transfusion
needed.
• Surgery remains a
definate indication and
best Rx –
OGDS/interventional
radiology fails.
Perforation
• Lifetime prevelance of
• S/S of septic shock
perforation in PUD pts
tacycardia,hypotension,
~5%.
lethargy,anuria,cyanosis
• Cause: NSAIDS, H.pylori • Simple surgical
• Bleeding, sudden onset
closures, intensive
of sudden severe, sharp
medical treatment, H
abdominal pain/
pylori eradication,
epigastric pain
NSAID withdrawal have
been reported to result
• Abd : generalized
in very low recurrence
tenderness, guarding,
rates.
rigidity, rebound
tenderness
Gastric outlet obstruction
• more commonly due to
malignancy than PUD.
• nausea, vomiting, bloating,
indigestion, epigastric pain,
and weight loss.
• endoscopy has the advantage
of being diagnostic and can
rule out possible malignancy.
• Malignant obstruction is
reported in 66% of patients.
• Outcomes may be improved
with effective ulcer therapy
with acid reduction and
eradication of H pylori.
• Surgery is associated with
significant morbidity and
mortality and should be
reserved for endoscopic
treatment failures.
• Surgical palliation for
malignant disease has poor
results and high rates of
morbidity and mortality.
HELICOBACTER PYLORI
HELICOBACTER PYLORI (HP)
• Gram negetive spiral bacteria
• Transmitted: fecal-oral ,oral-oral, mother to
child routes, iatrogenic.
• Highly prevalent in developing country &
lower socioeconomic .
• HP +ve subjects have 10-20% lifetime risk of
developing PUD.
PIC of halicobacter
Common Treatment Regimn
Regimen
Comment
Trile therapy
PPI; amoxicillin 1 g BID; clarithromycin
500mg BID for 10 -14 days
First line treatment
Sequential therapy
PPI and amoxicillin 1 g BID for 5 days
followed by PPI,
clarithromycin 500mg BID, tinidazole
500mg BID for 5 days
May be first line where macrolide
resistance is common
Quadruple therapy
PPI; bismuth 525mg QID; metronidazole
500mg QID;
and tetracycline 500mg QID for 14 days
Treatment for failure
• Overall ,triple therapy for 14 days has been shown to be
more effective at eradication of H pylori than dual therapy.
• A recent meta-analysis did not find a difference in H pylori
eradication rate between quadruple (PPI +bismuth
+metronidazole + tetracycline for 10–14 days) and triple
therapy (PPI+clarithromycin +azithromicin for 7–14
days).
• H. pylori has been found more frequently in
dyspeptic patients than in controls and has
been shown to affect acid secretion and, to a
lesser extent, gastric motility .
• “Test and treat strategy”(< 50YO, no alarming symp)
• In areas of low H. pylori prevalence (< 20%),
the empirical use of PPIs alone is considered
to be an equal option for symptom relief .
• NICE guidelines recommend initiation of a 4
week trial of full dose PPI therapy in patients
with uninvestigated dyspepsia.
Test available for H.pylori:
• Blood antibody test (enzyme-linked immunosorbent
assay [ELISA]). This test detects exposure to H pylori but
cannot be used to confirm successful treatment.
• Urea breath test. This test is adequate for screening
and for confirming cure following treatment. The use of PPIs
within 2 weeks of testing can interfere with the results.
• Stool antigen test. This test is adequate for screening
and for confirming cure following treatment.
• Stomach biopsy. Gold standard. It is adequate for
screening and for confirming cure. Results depend on the
number of biopsies and the experience of the pathologist.
RELATIONSHIP WITH ULCER
RELAPSES
• Studies showed that the rate of Helicobacter pylori
"reappearance" and of duodenal ulcer relapse up to
6 years after eradication of H. pylori.
(Archimandritis A, Balatsos V. 'Bacteriology and epidemiology of Helicobacter pylori infection. J Clin Gastroenterol. 1999;28(4):345.)
• Recent studies have suggested that the eradication
of H. pylori affects the natural history of duodenal
ulcer disease such that the rate of relapse decreases
markedly.
(Asaka M, Ohtaki T, Kato M. Causal role of Helicobacter pylori in peptic ulcer relapse. Gastroenterol. 1994 Jul;29 Suppl 7:134-8.)
• Chronic PUD was almost exclusively due to H. pylori
infection with up to 90% of duodenal ulcers and 70% of
gastric ulcers attributed to this bacterium.
• However, NSAIDs and aspirin are now responsible for
most ulcer disease in developed countries.
(d2- advances in public health, effective H.pylori eradication therapy).
EGD
(Esophagogastroduodenoscopy)
Alarm symptoms that require prompt
EGD in dyspeptic patients.
•
•
•
•
•
•
•
Anemia
Evidence of acute/chronic bleeding
Previous history of peptic ulcer
Odynophagia
Dysphagia
Recurrent or persistent vomiting
Unintentional weight loss
• Prompt endoscopy is recommended in patients with alarm
symptoms or patients over a threshold age (35-55 years).
• Men , younger age ↑prevalence at diagnosis of
upper GI malignancy
• Once failed a 48 week trial of PPI therapy (in an area of
low prevalence of H. pylori)/ failed to respond to
eradication of H. pylori (in an H. pylori endemic region)
upper endoscopy is indicated.
• Performing upper endoscopy during a symptomatic
period especially while the patient is off acid-suppressant
therapy is important to making a diagnosis of functional
dyspepsia by excluding other potential causes of
symptoms.
• Upper GI barium radiography:
inferior to upper endoscopy and is generally
not recommended as part of the work up for
dyspepsia.
Management of dyspepsia
Dyspepsia
Age>50 or
alarm symptoms
Age<50 and no
alarm symptoms
EGD
Dyspepsia
without GERD or
offending medication
High or intermediate
Prevalence
of H. pylori (>20%)
Use of NSAIDs
or other probable
offending medication
Typical GERD
symptoms
Trial off medication
or change to
an alternate medication
Full dose PPI trial
Continued symptoms despite
adequate PPI trial
Yes
Test and treat
for H. pylori
(Stool antigen or breath
test off PPI for >2 weeks)
Symptom
resolution
No
Negetive
Treat as GERD
Empiric trial of PPI
4–6 weeks
Test and treat
for H. pylori
(Stool antigen or breath
test off PPI for >2 weeks)
Empiric trial of PPI
4–6 weeks
No respond
No response
EGD
Abnormal
EGD
Treatment based
on endoscopic findings
Normal EGD
1. Biopsy for H. pylori (unless negative
H. pylori stool antigen or breath test
OFF PPI for greater than 2 weeks)
1. Reassurance
4. Evaluate and treat for IBS
2. Consider alternate causes of abdominal pain
3. Consider trial of low dose trycydic
antidepressant or antispasmotic
Note: diagnostic algorithm may differ based on regional cancer risk, gender, and age
of patient at presentation.
Refractory Functional Dyspepsia
• Patients who do not respond to empiric PPI
therapy, have normal upper endoscopy, and
who either are negative for H. pylori or have
cleared infection following treatment yet
continue to have dyspepsia represent a
challenging group.
• First, the diagnosis should be re-evaluated,
considering other disorders that may be
mistaken for dyspepsia.
• In the absence of an alternate disease,
reassurance and education of the patient
with functional dyspepsia becomes important.
• Although not validated in the functional
dyspepsia population, a positive physicianpatient interaction including reassurance can
reduce health care seeking behavior.
• Patients are often also educated to eat
smaller, more frequent meals to avoid gastric
distention and to avoid food that aggravates
symptoms.
TREATMENT
• Treatment of PUD consists of healing the ulcer and prevention of
complications. All plans should include appropriate management of PUD
risk factors.
• discontinue smoking; offered stress management programs and
counseled to avoid NSAIDs, aspirin, and alcohol abuse.
• Management of patients with PUD requires detection and eradication of
H pylori infection and the administration of antisecretory therapy,
preferably PPIs, for a minimum of 4 weeks.
• If patients recover after the first course of treatment, they should be
observed.
• If symptoms persist, antisecretory therapy with PPIs / histamine receptor
(H2) blockers should be continued for an additional 4 to 8 weeks, and
repeat EGD should be considered.
• re-evaluated for H pylori infection
NSAIDS
• Economic modeling suggests that Cox-1 NSAIDs + H2
blockers or Cox-1 NSAIDs + PPIs are the
most cost-effective strategies for avoiding
endoscopic ulcers in patients requiring long-term
NSAID therapy.
• PPIs are more effective than H2-blockers at standard
dosages in reducing the risk of gastric and duodenal
ulcer, and are superior to misoprostol in preventing
duodenal but not gastric lesions.
ASPIRIN
• Aspirin is commonly recommended to reduce the risk of
cardiovascular events.
• Several factors have been identified to increase the risk of
patients to develop aspirin-associated GI bleeding. These
include a history of previous GI ulcer, ulcer
complications, dyspepsia, H pylori infection, and
simultaneous use of aspirin with NSAIDs or clopidogrel.
• The use of enteric-coated or buffered aspirin does
not significantly decrease the risk of ulcer
complications due to its systemic effect.
• PPI + aspirin significantly reduces the risk recurrent
ulcer bleeding.
MEDICATION
CLASS
Medication
Typical dose
Precautions
Histamine -2
Receptor
blocker
Cimetidine
(Tagamet)
400 mg BID
High incidence of side
effects and potential for
drug interactions due to
inhibition of CYP450
150mg BD
Ranitidine (Zantac)
20 mg BD
Famotidine (Pepcid)
Proton pump
inhibitors
Omeprazole
20-40 mg daily
Altered metabolism of
medications through
CYP450
Lansoprazole
15-30 mg daily
Pantoprazole
40mg BD
Prostaglandin
s
Misoprostol
200 mg QID
Dose-dependent diarrhea
and abdominal pain
Avoid in fertile women and
during pregnancy
Other
medications
Sucralfate
1 g QID
Contains aluminum, should
be avoided in patients
with renal failure
Can prevent absorption of
other medications
INTERACTIONS H2 RECP ANTAGO
• Cimetidine (Tagamet) will inhibit drug metabolizing
enzymes and increase plasma concentrations for:
•
•
•
•
•
•
Benzodiazepines
Theophylline
Oral hypoglycemics
Tricyclic antidepressants
Propranolol
Tegretol
Coumadin
Caffeine
Dilantin
Flagyl
PROTON PUMP INHIBITORS
• Omeprazole (Prilosec)
• Lansoprazole (Prevacid)
• In a cost-simulation model, PPI therapy was
calculated as the most cost effective strategy
in dyspeptic patients at 30 years of age and in
areas of low H. pylori prevalence.
• For 60-year-old patients, H. pylori test and
treat was the most cost-effective strategy .
• Significantly better response rate for
omeprazole (31%) than for ranitidine (21%),
cisapride (13%) and placebo (14%).
MISOPROSTIL
• Prostaglandin analog that replaces
prostaglandins lost in stomach as result of
NSAID therapy
• Only indicated for NSAID induced ulceration
• Side effects : diarrhea and abdominal pain
SULCRALFATE - CARAFATE
• Viscous gel
• Adheres to ulcerated tissue and protects it
from acid / pepsin
• Minor side effect is constipation
• No major side effects
• May impede absorption of some drugs
NON-DRUG THERAPY
• Diet plays only a minor role in ulcer management.
• No conclusive evidence that caffeine containing
beverages promote ulcer formation or interfere with
recovery.
• Thought that alcohol can be harmful to lining of
stomach
• Beneficial to eat 5-6 small meals a day instead of 3
large ones to decrease fluctuations in gastric pH.
When to refer
• Patient ≤ 55 yo presenting with dyspepsia
without red flags, routine endoscopy is
unnecessary ( chances of devp GIT cancer is 1
in a million).
• Older than 55yo with new onset persistant
dyspepsia despite lifestyle & drug modification
& 4/52 Rx.
• Younger than 55 & symp unresponsive to full
dose PPI ,HP eradication,& lifestyle
modification where concern exists about
diagnosis.
Case Scenario
Case scenario:
•
•
•
•
•
•
•
•
A 60 year old man
k/o :Diabetes Mellitus and Hypertension for 10 years
c/o: epigastric discomfort for 1 month duration.
The pain worsened at night and would awaken him from
sleep.
He denied of other GIT symptoms such as malena, lost of
weight or anorexia.
He also suffered Left hemiparesis from Ischaemic Stroke
since 3 months ago.
His current treatment is metformin 1gm bd, perindopril
4mg od, aspirin 150mg od and Simvastatin 20mg ON.
Currently, his vital signs are stable and examination
including abdomen was unremarkable.
Proceed with management
• This history is typical of dyspepsia.
• Non-pharmacology :
stop aspirin
Explain that dyspepsia is a common condition
that usually responds well to treatment
Offer lifestyle advice, including smoking
cessation, weight loss, reduced alcohol and
caffeine intake, and regular exercise.
• Pharmacological:
 Aspirin + PPI
Caspirin + PPI
Ticlid