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.