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
•
E.g. Maalox = Mg(OH)2 +
Al(OH)3
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)
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,famotidine
-Impotence, gynaecomastia & confusion less 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

Stool antigen test

Serology

Endoscopy – CLO test
95% sensitive & specific
92% sensitive & specific
80% sensitive & specific
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 7
days
E.g. of PPI: Lansoprazole 30mg BD
PO
Subsequent failures handled on
individual basis with advice from
gastro/micro
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
& tetracycline
GI side effects, ↓ effectiveness OCP, 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.