Dyspepsia

Dyspepsia, Peptic Ulcer
Disease and
Helicobacter Pylori
Pharmacology & Therapeutics February
2007
Dyspepsia
40% of all adults
4% GP consultations
10% further investigations
10-20% NSAID users
Endoscopy findings
15% Duodenal or Gastric ulcer
15% Oesophagitis = GORD
30% Gastritis duodenitis or hiatus

hernia
30% Normal = functional dyspepsia
Pathogenesis of Dyspepsia
Factor
Treatment approach
Infection with H. pylori
Eradication of H. pylori
infection, e.g. triple tx
gastric HCl secretion
HCl secretion or
neutralizing it, e.g. H2
antagonists, pirenzepine,
antacids , PPIs
Inadequate mucosal
defence against gastric
HCl
Agents that protect

gastric mucosa, e.g.
sucralfate
Altered gastric motility
Prokinetic agents eg
metoclopramide
Gastric acid secretion
Helicobacter Pylori
Symptomatic
treatment
Antacids
MOA: Weak bases that

react with gastric acid to
form H20+salt. pepsin
activity as pepsin
inactive at pH>4
Symptom relief,
liquids>tablets
Drug
Side effect
Magnesium
severe osmotic
diarrhoea
(therefore
combined with
AlOH)
drug
absorption
Aluminium
phosphate,
absorption of
tetracycline,
thyroxine &
chlorpromazine
, constipation
Calcium
Ca in blood &
urine (high
doses)
E.g. Maalox = Mg(OH)2

+ Al(OH)3
Mucosal Protective Agents

1) Sulcralfate
MOA: Binds to positively charged proteins present on damaged mucosa
forming a protective coat
Useful in stress ulceration
As effective as H2-R antagonists/high dose antacids
SE: Constipation
absorption of cimetidine, digoxin, phenytoin & tetracycline
2) Bismuth
MOA: Antimicrobial action. Also inhibit pepsin activity, mucus secretion
& interact with proteins in necrotic mucosal tissue to coat & protect the
ulcer crater
Additional agents
Antifoaming agent
Dimethicone to relieve flatulence (surfactant)
Alginates
- form a raft on surface of stomach contents to reduce reflux
Carbenoxolone
- liquorice derivative ? Alters mucin s/e H2O retention
K+
H2-receptor antagonists
Drug
Side effects
Cimetidine
-reversible impotence, gynaecomastia &

sperm count (high doses) (nonsteroidal
antiandrogen)
-mental status abnormalities-confusion,
hallucinations (elderly/renal impairment)
-leukopenia & thrombocytopenia (rare)
-cytochrome P450 inhibitor (e.g. impairs
metabolism of warfarin, theophylline &
phenytoin)
Ranitidine,famotidi -Impotence, gynaecomastia & confusion less

ne
frequently than cimetidine.
-Little interference with cytochrome P450
-Reversible drug-induced hepatitis with all H2antagonists
Proton-pump Inhibitors (PPI)
MOA: block parietal cell H+/K+ ATPase enzyme system

(proton pump) secretion of H+ ions into gastric lumen
More effective than H2-antagonists or antacids
Used in antimicrobial regimens to eradicate H. pylori
SE: n&v, diarrhoea, dizziness, headaches,

gynaecomastia & impotence (rare), thrombocytopenia,
rashes
Helicobacter Pylori
95% Duodenal ulcers
70% Gastric ulcers
10% Non-ulcer dyspepsia
Treatment benefits gastritis more

than reflux symptoms
Diagnosing H. pylori
Urea breath test 95% sensitive & specific
Stool antigen test 92% sensitive & specific
Serology 80% sensitive & specific
Endoscopy CLO test 98% sensitive & specific

(urea and phenol red, a dye that turns pink in a pH of 6.0 or
greater)
H. Pylori Eradication
1st line eradication tx
for H. pylori
2nd line tx
Preferred tx= PPI PO +

Clarithromycin 500mg BD PO +
Amoxicillin 1 gm BD PO for 7
days
PPI + Bismuth 120mg QDS PO

+ Metronidazole 500mg TDS
PO + Tetracycline 500mg QDS
PO for 7 days
If Penicillin allergic= PPI +

Clarithromycin 500mg BD PO +
Metronidazole 400mg BD PO for Subsequent failures handled
7 days
on individual basis with advice
from gastro/micro
E.g. of PPI: Lansoprazole 30mg
BD PO
H. Pylori eradication
1 week triple-therapy regimens eradicate H.

Pylori in >90% cases. Usually no need for
continued antisecretory tx unless ulcer
complicated by bleeding/perforation
2 week triple-therapy offer higher eradication

rates cf 1 week but SE common & poor
compliance
2-week dual-therapy with PPI & antibacterial

produce low rates of H. pylori eradication & not
recommended
H. pylori eradication
Treatment failure may be due to

- Resistance to antibacterial drugs
- Poor compliance
Drug
Side effects
Bismuth
n&v, unpleasant taste, darkening of tongue &

stools, caution in renal disease
Metronidazole n&v, unpleasant taste, effectiveness OCP, care

with lithium/warfarin
Amoxicillin
GI side effects, effectiveness OCP,
& tetracycline pseudomenbranous colitis
Lansoprazole
effectiveness OCP
Practical Management
of dyspepsia
Who needs
endoscopy?
GI bleeding
Unintentional weight loss
Dysphagia
Persistent vomiting
Iron deficiency anaemia
Epigastric mass
>55 with unexplained persistent/recent onset

dyspepsia
PUD on endoscopy
Stop NSAIDs
Start full dose PPI for 2 months
Eradication treatment if H Pylori

positive
Repeat endoscopy for gastric ulcer 2%

cancer risk
GORD on endoscopy
Lifestyle advice
Full dose PPI for 1-2 months
H Pylori Eradication may not benefit reflux symptoms
If recurrence - lowest dose PPI to control symptoms
GORD
GORD = Symptoms of heartburn
General advice includes AVOIDING
Drug Tx
Meals
antacids=+/-alginic
at night, lying down after
meals
Elevate head of bed
Heavy lifting, tight clothing,
bending
Being overweight
Smoking (nicotine relaxes lower
oesophageal sphincter)
Aggravating substances (spicy
foods, C2H5OH)
Drugs which encourage reflux
(e.g. antimuscarinic, smooth
muscle relaxants, theophylline)
acid
Pro-kinetic agent, e.g.
metoclopramide
H2-antagonist
PPI
If severe sx when tx stopped, or
bleed from oesophagitis or
stricture maintenance tx with PPI
or surgery may be necessary
NSAID Induced
Dyspepsia
10-20% develop endoscopically visible PUD
1-5% perforation or major bleeding
Endogenous prostaglandins (PGE2 & I2) contribute to GI mucosa

integrity by
- stimulation of mucus & bicarbonate secretion
- maintenance of blood flow (allows removal of luminal H-ions)
- prevent luminal H-ions from diffusing into the mucosa
- gastric acid secretion
- helping to repair damaged epithelium
NSAID Induced
Dyspepsia
Elderly >65 years
History PUD
Other drugs eg bisphosphonates, Steroids
PPI or misoprostol protection for at risk
Consider screening & eradicating H Pylori

infection
Prostaglandin analogues
Misoprostol = synthetic prostaglandin E1 analogue

Prevents NSAID induced ulcers & heals chronic GU & DU
SE: Abdo pain, n&v, diarrhoea, abortifacient (produces
uterine contractions)
Non ulcer dyspepsia
Treat H pylori (no routine retesting)
Symptomatic treatment
PPI (proven benefit)
Prokinetic agent eg
metoclopramide (probable benefit)
Dyspepsia without alarm

symptoms
Lifestyle advice
Antacids and medication review
Empiric PPI
Test and treat for H Pylori
Shah, R.
BMJ 2007;334:41-43
Copyright 2007
BMJ Publishing Group Ltd.

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Dyspepsia, Peptic Ulcer

40% of all adults

10% further investigations

10-20% NSAID users

15% Duodenal or Gastric ulcer

15% Oesophagitis = GORD

30% Gastritis duodenitis or hiatus

30% Normal = functional dyspepsia

Infection with H. pylori

gastric HCl secretion

Agents that protect

Altered gastric motility

Gastric acid secretion

MOA: Weak bases that

E.g. Maalox = Mg(OH)2

Mucosal Protective Agents

-reversible impotence, gynaecomastia &

Ranitidine,famotidi -Impotence, gynaecomastia & confusion less

Proton-pump Inhibitors (PPI)

MOA: block parietal cell H+/K+ ATPase enzyme system

More effective than H2-antagonists or antacids

Used in antimicrobial regimens to eradicate H. pylori

SE: n&v, diarrhoea, dizziness, headaches,

95% Duodenal ulcers

70% Gastric ulcers

10% Non-ulcer dyspepsia

Treatment benefits gastritis more

Urea breath test 95% sensitive & specific

Stool antigen test 92% sensitive & specific

Serology 80% sensitive & specific

Endoscopy CLO test 98% sensitive & specific

Preferred tx= PPI PO +

PPI + Bismuth 120mg QDS PO

If Penicillin allergic= PPI +

1 week triple-therapy regimens eradicate H.

2 week triple-therapy offer higher eradication

2-week dual-therapy with PPI & antibacterial

Treatment failure may be due to

n&v, unpleasant taste, darkening of tongue &

Metronidazole n&v, unpleasant taste, effectiveness OCP, care

Unintentional weight loss

Iron deficiency anaemia

>55 with unexplained persistent/recent onset

Start full dose PPI for 2 months

Eradication treatment if H Pylori

Repeat endoscopy for gastric ulcer 2%

Full dose PPI for 1-2 months

H Pylori Eradication may not benefit reflux symptoms

If recurrence - lowest dose PPI to control symptoms

General advice includes AVOIDING

at night, lying down after

10-20% develop endoscopically visible PUD

1-5% perforation or major bleeding

Endogenous prostaglandins (PGE2 & I2) contribute to GI mucosa

Elderly >65 years

Other drugs eg bisphosphonates, Steroids

PPI or misoprostol protection for at risk

Consider screening & eradicating H Pylori

Misoprostol = synthetic prostaglandin E1 analogue