Dyspepsia, Peptic Ulcer Disease And: Helicobacter Pylori

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 Agents that protect gastric
against gastric HCl mucosa, e.g. sucralfate
Altered gastric motility Prokinetic agents eg

metoclopramide
Gastric acid secretion
Helicobacter Pylori
Symptomatic treatment
Antacids
Drug Side effect
Magnesium severe osmotic
MOA: Weak bases that diarrhoea
react with gastric acid to (therefore
form H20+salt. pepsin combined with
activity as pepsin inactive at AlOH)
pH>4 drug absorption
Symptom relief, Aluminium phosphate,

liquids>tablets absorption of
tetracycline,
thyroxine &
E.g. Maalox = Mg(OH)2 + chlorpromazine,
Al(OH)3 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 H2-
antagonists
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 2nd line tx

H. pylori
Preferred tx= PPI PO + PPI + Bismuth 120mg QDS PO +
Clarithromycin 500mg BD PO + Metronidazole 500mg TDS PO +
Amoxicillin 1 gm BD PO for 7 days Tetracycline 500mg QDS PO for 7
days
If Penicillin allergic= PPI +
Clarithromycin 500mg BD PO +
Metronidazole 400mg BD PO for 7
days Subsequent failures handled on
individual basis with advice from
E.g. of PPI: Lansoprazole 30mg BD gastro/micro
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, pseudomenbranous
& tetracycline 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 at night, lying down after meals antacids=+/-alginic acid
Elevate head of bed Pro-kinetic agent, e.g. metoclopramide
Heavy lifting, tight clothing, bending H2-antagonist
Being overweight PPI
Smoking (nicotine relaxes lower If severe sx when tx stopped, or bleed

oesophageal sphincter) from oesophagitis or stricture
Aggravating substances (spicy foods, maintenance tx with PPI or surgery may
C2H5OH) be necessary
Drugs which encourage reflux (e.g.
antimuscarinic, smooth muscle
relaxants, theophylline)
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.

Dyspepsia, Peptic Ulcer Disease And: Helicobacter Pylori

Uploaded by

Copyright:

Available Formats

Dyspepsia, Peptic Ulcer Disease And: Helicobacter Pylori

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Dyspepsia, Peptic Ulcer Disease And: Helicobacter Pylori

Uploaded by

Copyright:

Available Formats

Dyspepsia, Peptic Ulcer

Disease and Helicobacter

Pharmacology & Therapeutics February 2007

40% of all adults

15% Duodenal or Gastric ulcer

Factor Treatment approach

Infection with H. pylori Eradication of H. pylori

gastric HCl secretion HCl secretion or

Altered gastric motility Prokinetic agents eg

Symptom relief, Aluminium phosphate,

Drug Side effects

Cimetidine -reversible impotence, gynaecomastia & sperm count

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, gynaecomastia &

95% Duodenal ulcers

Urea breath test 95% sensitive & specific

Stool antigen test 92% sensitive & specific

Serology 80% sensitive & specific

Endoscopy CLO test 98% sensitive & specific

1st line eradication tx for 2nd line tx

1 week triple-therapy regimens eradicate H. Pylori

2 week triple-therapy offer higher eradication rates

2-week dual-therapy with PPI & antibacterial

Drug Side effects

H Pylori Eradication may not benefit reflux symptoms

General advice includes AVOIDING Drug Tx

Heavy lifting, tight clothing, bending H2-antagonist

Being overweight PPI

Smoking (nicotine relaxes lower If severe sx when tx stopped, or bleed

Endogenous prostaglandins (PGE2 & I2) contribute to GI mucosa integrity

Elderly >65 years

PPI or misoprostol protection for at risk

Misoprostol = synthetic prostaglandin E1 analogue

Treat H pylori (no routine retesting)

You might also like