EVIDENCE BASED PHARMACY PRACTICE

Evidence

Evidence-based Pharmacy Practice (EBPP):

PEPTIC ULCER DISEASE

Ilse Truter
Drug Utilization Research Unit (DURU), Department of Pharmacy, Nelson Mandela Metropolitan University

A peptic ulcer is an erosion in a segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or
the first few centimeters of the duodenum (duodenal ulcer), that penetrates through the muscularis mucosae.1
Symptoms typically include burning epigastric pain that is often relieved by food.1

Nearly all ulcers are caused by Helicobacter pylori (H pylori) infection or non-steroidal anti-inflammatory drug
(NSAID) use. H pylori has been clearly associated with both gastric and duodenal ulcers, and, in the absence of
NSAIDs, eradication of the organism results in long-term healing with re-infection being rare.2 H pylori is said to
account for 80% of all gastric or stomach ulcers and more than 90% of all duodenal ulcers.3,4 Confirmation of the
presence of H pylori prior to eradication therapy is recommended.2

Definition of peptic ulcer disease

A peptic ulcer indicates an interruption in the continuity of the
intestinal mucosa as a result of the action of acids and pepsin.5
The ulceration can occur in the stomach, duodenum and sometimes in the jejunum.5 Ulcers may range in size from several
millimeters to several centimeters.1 Ulcers are delineated from
erosions by the depth of penetration (erosions are more superficial and do not involve the muscularis mucosae).
Gastritis indicates inflammation of the gastric mucosa, without
ulceration.5 Gastritis is usually a precursor of ulceration, but
either condition can occur in isolation.5

Epidemiology of peptic ulcer disease

Ulcers can occur at any age, including infancy and childhood, but
are most common in middle-aged adults.1 Peptic ulcer (gastric
and duodenal) occurs most commonly in patients aged 30 to 50
years6, although patients over the age of 60 years account for
80% of deaths even though they only account for 15% of cases7.
Prevalence has shifted from predominance in males to similar
occurrences in both sexes.8 Lifetime prevalence is approximately
11% to 14% for men and 8% to 11% for women.8

Aetiology/pathophysiology

H pylori and NSAIDs disrupt the normal mucosal defense and

repair, making the mucosa more susceptible to acid.1 H pylori
infection is present in 80% to 90% of patients with duodenal
ulcers and 70% to 90% of patients with gastric ulcers.1 If H pylori
is eradicated, only 10% to 20% of patients have recurrence of
peptic ulcer disease, compared with 70% recurrence in patients
treated with acid suppression alone.1
Although the cause of peptic ulceration in some patients is apparent
(such as aspirin usage), in most cases the pathogenesis is unknown. There are, however, a number of factors which have been
identified as possibly leading to peptic ulceration, namely5,8:

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Helicobacter pylori infection: As already mentioned, H pylori is present in the mucosa of 80% of
patients with peptic ulceration and gastritis, while it is
only present in 20% of the normal healthy population.
Genetic tendency: A genetic tendency occurs
especially in the case of duodenal ulceration.
Furthermore, a family history exists in 50% to 60% of
children with duodenal ulcer.1
Medicine: Medicine such as aspirin, NSAIDs and
corticosteroids can cause peptic ulceration.
Alcohol: Chronic drinkers of alcohol develop
ulceration, while the occasional drinker normally
only develops gastritis. Although alcohol is identified
as a strong promoter of acid secretion, no definite
data link moderate amounts of alcohol to the development or delayed healing of ulcers.1
Cigarette smoking1: It is a risk factor for the development of ulcers and their complications. In addition, smoking impairs ulcer healing and increases
the incidence of recurrence. Risk correlates with the
number of cigarettes smoked per day.
Stress: Severe physiologic stress can cause peptic
ulcer disease, for example burns, central nervous
system trauma, surgery and severe medical illness.8
Bile salts and pancreatic enzymes: They can
cause ulceration when they leak back into the
stomach on account of an inefficient pyloric sphincter, or when stasis of the intestinal bolus occurs as a
result of partial obstruction.
Toxins secreted by micro-organisms: e.g. toxins
secreted in chronic gastroenteritis.
Hypersecretory states. This is an uncommon
cause. Examples include gastrinoma (ZollingerEllison syndrome), multiple endocrine neoplasia
(MEN-I), antral G cell hyperplasia, systemic mastocy-

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EVIDENCE BASED PHARMACY PRACTICE

tosis and basophilic leukemias. Very few patients have

hypersecretion of gastrin (Zollinger-Ellison syndrome).1
Chronic conditions: Diseases associated with an
increased risk of peptic ulcer disease include cirrhosis,
chronic obstructive pulmonary disease, renal failure and
organ transplantation.8
Rare conditions: Other rare, miscellaneous causes
include radiation-induced or chemotherapy-induced
ulcers, vascular insufficiency and duodenal obstruction.8

These factors weaken the normal protective barrier of the

mucous membrane of the stomach and small intestine and
may cause increased secretion of acid and pepsin, with
resulting inflammation and subsequent ulceration.5

Diagnosis of peptic ulcer disease

Symptoms depend on ulcer location and patient age. Many
patients, particularly elderly patients, have few or no symptoms.1 Pain is however the most common symptom, often
localised to the epigastrium or mid-epigastrium and relieved
by food or antacids.1,6 The pain is described as burning,
gnawing, constant or annoying, or sometimes a sensation of
hunger.1,6 The course is usually chronic and recurrent. Only
about 50% of patients present with the characteristic pattern
of symptoms.1 Table I distinguishes between the symptoms
of gastritis, gastric and duodenal ulcer.

approximately an hour after eating), and is generally relieved by

antacids or food but aggravated by alcohol and caffeine.6,7
Weight loss and gastrointestinal bleeding occur more
frequently with gastric ulcers.6 Patients can experience
weight loss of 5 kg to 10 kg and although this could indicate
carcinoma, especially in people over 40 years, on investigation a benign gastric ulcer is found most of the time.7
Duodenal ulcers tend to produce more consistent pain. Pain
is absent when the patient awakens but appears midmorning, is relieved by food, but recurs two to three hours
after a meal.1 Pain that awakens a person at night, a few
hours after falling asleep, is also common and is highly
suggestive of duodenal ulcer.1 The pain then usually
subsides by morning and is often relieved after eating.6 This
is not commonly noticed in gastric ulceration.7 In neonates,
perforation or haemorrhage may be the first manifestation of
duodenal ulcer. Haemorrhage may also be the first recognised
sign in later infancy and early childhood, although repeated
vomiting or evidence of abdominal pain may be a clue.1

Gastric ulcer symptoms often do not follow a consistent pattern

(for example, eating sometimes exacerbates rather than
relieves, pain).1 This is especially true for pyloric channel
ulcers, which are often associated with symptoms of obstruction
(for example bloating, nausea and vomiting) caused by
oedema and scarring.1 In general, however, in gastric ulcers,
pain typically starts whenever the stomach is empty (usually

Diagnosis of peptic ulcer is by patient history, and confirmed by

endoscopy and testing for H pylori. Table II gives a summary of
persons that should be tested for H pylori. The following are
examples of tests that can be done for H pylori8,9,10:
Carbon-13 urea breath tests detect active H pylori
infection by testing for the enzymatic activity of bacterial
urease. In the presence of urease produced by H pylori,
labeled carbon dioxide is produced in the stomach,
absorbed into the bloodstream, diffused into the lungs
and exhaled.
Stool or faecal antigen testing identifies active H pylori
infection by detecting the presence of H pylori antigens in
stools.

Table I: Differences between

gastritis, gastric and duodenal ulcers5

Table II: Persons who should be tested for H pylori3

Property
Pain:
Localisation

Gastritis

Epigastric

Gastric Ulcer

Duodenal
Ulcer

Epigastric

Epigastric or
umbilical
Spreading
Substernal
Substernal
Back
Nature
Burning
Sharp, stabbing Dull
Frequency
Especially after Every day
Periodic, somecausative fac- Pain more se- times persistent
tors, e.g. alcohol vere
Response to in- Pain similar or Seldom
Pain improves
gestion of food better
Night time pain Seldom
Relieves pain
Often
Antacids
Relieves pain
Relieves pain
Family history

Seldom

Occasionally

Age

Any age

Older than 45 Between 30 and

years
40 years

Ability to eat af- Often

ter vomiting

Always

Strength of recommendation for testing

Population

Recommended

Evidence of active duodenal or gastric

ulcer
Asymptomatic patients who have a
documented history of ulcer disease
and are on antisecretory therapy
Family history of gastric cancer
Low-grade gastric mucosa-associated
lymphoid tissue (MALT) lymphomas

Should be considered

Symptoms suggestive of peptic ulcer

disease
New-onset dyspepsia, if patient is under the age of 50 years and has no
symptoms of malignancy

Not recommended

Chronic symptoms suggestive of

gastro-oesophageal reflux disease

Often

Occasionally

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EVIDENCE BASED PHARMACY PRACTICE

Evidence

Serology, which is immunoglobulin G (IgG) based, can be

measured in serum, plasma or whole blood. It will,
however, not distinguish between a previous or a current
infection.
Biopsy-based urease tests, which are invasive and can
only be done at gastroscopy or in the acute hospital
setting. There are two methods for this test. In the CLO
test (Campylobacter-like organisms test, the rapid
urease test) a fragment of mucosal membrane is placed
into a special jelly which undergoes a colour change in
10 to 20 minutes, or the specimen is sent for histology
which may take up to 24 hours to obtain the result.

Endoscopy allows for biopsy or cytologic brushing of gastric

and oesophageal lesions to distinguish between simple
ulceration and ulcerating stomach cancer. Stomach cancer
may present with similar signs and symptoms and must be
excluded, especially in patients who are over 45 years of
age, have lost weight, or report severe or refractory symptoms.1 The incidence of malignant duodenal ulcer is extremely low, therefore biopsies of lesions in that area are
generally not warranted. Endoscopy can also be used to
definitely diagnose H pylori infection, which should be
sought when an ulcer is detected.
Gastrin-secreting malignancy and Zollinger-Ellison syndrome should be considered when there are multiple ulcers,
when ulcers develop in atypical locations or are refractory to
treatment, or when the patient has prominent diarrhoea or
weight loss. Serum gastrin levels should be measured in
these patients.1

Counselling approach to follow

A thorough history regarding habits and medication usage should be taken, a physical examination can be performed and, if appropriate,
laboratory/diagnostic tests (often endoscopy) may be
conducted to exclude other conditions. The overall aim is to
reduce epigastric pain, to improve the patients quality of life
by identifying, treating and/or eliminating the underlying
cause of the peptic ulceration, and to use pharmacological
therapy when indicated. This should be accomplished
without adverse effects or with clinically acceptable adverse
effects. A list of aspects that should be addressed in a
patient assessment history is given in Table III.
If the pharmacist is convinced that a patient is only suffering
from gastritis, therapeutic treatment can be offered. If a
peptic ulcer is suspected, the pharmacist can provide
temporary, symptomatic treatment, followed by referral to a
medical practitioner. Empiric therapy is therefore often
begun without a definite diagnosis.

When to refer

The following are indicative of referral:

All patients with a new or recurring ulcer should be
referred to a medical practitioner for diagnosis and

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Table III: Specific questions to ask the patient with suspected peptic ulcer diease
Aspect

Question

Pattern, duration and se- Describe the location of the pain

verity of symptoms
Describe the type of pain that you are
experiencing (for example, constant or
intermittent, gnawing or stabbing)
Are you sometimes awakened by the
symptoms after a few hours of falling
asleep?
Is the pain relieved or worsened by the
intake of food?
Onset

When did the symptoms start?

Has there been any change to your
work routine, stress levels, use of medicine, eating or drinking habits?

Associated factors and Do you have any other symptoms (for

conditions
example, blood in your stools, nausea
or vomiting)?
What current or preceding illnesses do
you suffer from?
What medicine do you take?
Are any other family members experiencing similar symptoms?
Previous similar symp- Have you experienced similar symptoms
toms before? If yes, what was the
cause?
Previous and current ac- What are you taking or doing to relieve
tions to relieve symptoms the symptoms?

treatment. The pharmacist should only offer short-term

symptomatic treatment (one to two days).5
Since a high percentage of gastric carcinoma occurs as a
result of gastric ulceration, early referral of a suspected
gastric ulcer is an urgent necessity.
Any complications such as acute bleeding, perforation or
obstruction constitute an emergency which necessitates
urgent medical attention.

The following are potential complications of an undiagnosed

and untreated peptic ulcer5:

Chronic, slow gastrointestinal bleeding with resulting

anaemia (tiredness and pallor) and occult blood in the
stools.
Reduced food intake due to pain, with resultant weight
loss and emaciation.
Complications specifically in cases of ulceration:
o Acute bleeding with:
- Clear blood in stools
- Haematemesis
- Hypovolaemic shock and death
o Perforation of the ulcer with peritonitis. An acute
abdomen presents.
o On healing, fibrosis and stenosis can occur, with
partial or complete obstruction.
o Gastric carcinoma often presents as a gastric ulcer.

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EVIDENCE BASED PHARMACY PRACTICE

Evidence

Available treatment options for peptic ulcer

disease
The choice of the most appropriate treatment for peptic ulcer
disease depends on the cause. The most effective therapy is
generally to treat or eliminate the underlying cause (in the
majority of cases H pylori).

With current pharmacological therapy, the number of patients

requiring surgery has declined dramatically during the last
number of years. Indications for surgery include perforation,
obstruction, uncontrolled or recurrent bleeding, and symptoms that do not respond to drug therapy.1 Surgery consists
of a procedure to reduce acid secretion, often combined with
a procedure to ensure gastric drainage.1

Non-pharmacological management

Smoking should be discontinued, and alcohol consumption

discontinued or limited to small amounts of dilute alcohol.1
Stress reduction counseling may be helpful in individual
cases but is not needed routinely.8 There is limited or no
evidence that changing the diet (the so-called ulcer diets)
speeds ulcer healing or prevents recurrence. However,
many medical practitioners recommend eliminating those
foods only that cause distress.1 The following are precautionary dietary measures that can be taken5:
Eat small meals at regular times, and include snacks
between meals.
Eat slowly and chew thoroughly.
Adjust the diet to the severity of the condition. During an
acute phase, the following should be avoided:
- Strong, excessively hot tea or coffee, alcohol and
caffeine (especially on an empty stomach).
- Spices, such as curries, and blue cheese.
- Roasts and fatty foods, for example sausage, oily fish
and pasta.
- Green and dried fruits as well as fibrous vegetables,
for example onions, radishes and celery.
Ensure that sufficient vitamin C in the form of fruit,
vegetables and fresh juices is taken.
Prevent anaemia by eating foods rich in iron, such as
liver.
Rest for 15 minutes after each meal.
If possible, avoid emotional stress.

Pharmacological treatment

Pharmacological treatment of both gastric and duodenal

ulcer involves acid suppression, eradication of H pylori (if
present) and the avoidance of NSAIDs.1 For duodenal
ulcers, it is particularly important to suppress nocturnal acid
secretion.1 A number of medicines are effective in reducing
acid secretion but vary in cost, duration of therapy and
convenience of dosing. In addition, mucosal protective
medicine (for example, sucralfate) may be used.
Antacids
Antacids neutralise gastric acid and reduce pepsin activity.1
In addition, some antacids adsorb pepsin. Antacids relieve

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symptoms, promote ulcer healing and reduce recurrence.1

The efficacy of antacids compares well with some of the
other ulcer-healing drugs. Antacids remain safe, simple and
effective agents for the symptomatic treatment of gastricrelated symptoms. Studies have shown that lower doses
may be as effective as the high doses formerly recommended. In practice, antacids have been superseded by H
pylori eradication strategies in peptic ulcer disease and are
used only for short-term symptom relief.
There are two types of antacids: absorbable and nonabsorbable.1 Absorbable antacids (for example, sodium
bicarbonate and calcium carbonate) provide rapid, complete
neutralisation but may cause alkalosis and should only be
used for one to two days. Non-absorbable antacids (for
example, aluminium or magnesium hydroxide) cause fewer
systemic side effects and are preferred.
Proton pump inhibitors
The proton pump inhibitors (PPIs) are the most potent
suppressors of gastric acid secretion.2 Examples include
omeprazole, esomeprazole, lansoprazole, pantoprazole and
rabeprazole. They act by irreversibly binding to and inhibiting the H+/K+-ATPase enzyme of the gastric parietal cell.
These drugs can completely inhibit acid secretion and have
a long duration of action. They promote ulcer healing and
are key components of H pylori eradication regimens. PPIs
have replaced H2-blockers in most clinical situations because of greater rapidity of action and efficacy.
H2-receptor antagonists
The H2-receptor antagonists reduce gastric secretion by
blocking the action of histamine at the H2-receptors in the
parietal cells of the stomach.2 Gastric acid secretion in
response to other secretagogues (for example, acetylcholine
and gastrin) is also reduced. Examples include cimetidine,
ranitidine and nizatidine. H2-blockers are well absorbed from
the gastrointestinal tract, and duration of action is proportional to the dose (ranging from 6 to 20 hours).1
Prostaglandins
The production of protective prostaglandins is inhibited by
NSAIDs. This is thought to be the mechanism of NSAIDinduced ulceration.4 Certain prostaglandins, especially
misoprostol, inhibit acid secretion and enhance mucosal
defense.1 Misoprostol, a synthetic prostaglandin E1 analogue, is indicated for protection against NSAID-associated
gastric and duodenal ulceration. Misoprostol was found to
decrease the incidence of serious gastrointestinal events
(relative risk 0.57, 95% confidence interval 0.36-0.91).9
Patients at high risk for NSAID-induced ulcers (for example,
elderly patients, those with a history of ulcer or ulcer complication, or those also taking corticosteroids) are candidates
for taking misoprostol. The major drawback of misoprostol is
the incidence of diarrhoea, particularly at the higher dose of
200 g four times daily.4

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Sucralfate
Sucralfate, a sucrose-hydrogen-sulphate-aluminum complex,
is a mucosal protective agent. It has a local protective action
on the ulcer base, without the side-effects that may occur
with systemic agents.2 In the stomach, a paste-like gel is
formed from a reaction with hydrochloric acid, which adheres
to the base of ulcer craters (both in the stomach and duodenum), protecting ulcer epithelium from ulcerogenic substances such as gastric acid, pepsin and bile.2 It also directly
adsorbs bile and pepsin. It has no effect on acid output or
gastrin secretion.
Bismuth subcitrate
Bismuth subcitrate has a high affinity for damaged tissue and
forms a visible coating in the base of the ulcer crater,
protecting the ulcer from gastric acid, pepsin and bile. Its
efficacy in the treatment of duodenal and gastric ulcers
compares favourably with H2-receptor antagonists and other
ulcer healing agents.2

Helicobacter pylori eradication

Eradication of H pylori has been shown to increase the rate
of healing of duodenal ulcers compared with acid suppression alone.4 After four to eight weeks, an average of 69% of
duodenal ulcer patients receiving acid suppression will be
healed.4,13 Eradication of H pylori increases this by a further
5.4%, a number needed to treat (NNT) of 18.4,13 The principal
benefit of eradication however, is the reduction in ulcer
recurrence rates, thereby reducing the need for long-term
acid suppression therapy.
H pylori eradication therapy does not increase gastric ulcer
healing in H pylori positive patients when compared with
acid suppression alone in trials of 4 to 8 weeks duration.13 H
pylori eradication therapy does however reduce gastric ulcer
recurrence in H pylori positive patients.13
H pylori eradication is achieved by a combination of antibiotic therapy and acid suppression. Various combinations of
dual, triple, one and two week therapies have been used in
South Africa. High eradication rates (in excess of 90%) have
been reported with 7-day regimens comprising2:
a PPI, plus
two of the following antibiotics:
- clarithromycin 500 mg twice daily
- amoxicillin 1 g twice daily
- metronidazole 400 mg twice daily
Gastric ulcers and ulcers complicated by haemorrhage or
perforation may require the PPI therapy to be continued for
one month (or until the ulcer has healed).2
If a PPI is contraindicated, an alternative regimen is2:
ranitidine (300 mg daily for 7 days), plus
bismuth subcitrate (120 mg 6 hourly for 7 days), plus
two antibiotics (as above).

SA Pharmaceutical Journal January/February 2009

Evidence-based guidelines
The efficacy of the various H pylori eradication regimens is
reviewed in the full National Institute for Health and Clinical
Excellence (NICE) guideline on dyspepsia.12,13 PRODIGY
recommendations for the first-line treatment of peptic ulcer
disease mirror those advised by NICE10 and will not be
discussed in detail. In Figure 1 the management flowchart
for gastric ulcer according to the NICE guidelines is given,
and in Figure 2 the management flowchart for duodenal
ulcer.
Table IV provides an overview of the NICE guidelines on
initial therapy for peptic ulcer disease. One week triple
therapy in a regimen containing clarithromycin is considered
to be the gold standard.4 PPI-based dual therapy has been
shown to be less effective than triple therapy, and regimens
containing a PPI, amoxicillin and metronidazole are less
effective than clarithromycin-based regimens.4
NICE guidelines12,13 recommend either of the following for
seven days as first line therapy:
PPI full dose twice daily, amoxicillin 1 g twice daily and
clarithromycin 500 mg twice daily; or
PPI full dose twice daily, metronidazole 400 mg twice
daily and clarithromycin 250 mg twice daily.
These regimens are equally effective and achieve eradication in 80% to 85% of patients.4,13 Although the second
regimen is less expensive than the first one, there are some
concerns that the second therapy may induce resistance to
both metronidazole and clarithromycin.4 Resistance to
amoxicillin is not as common.4
Increasing the length of therapy to 14 days increases
eradication rates by approximately 10% although it was not
found to be cost-effective when modeled by NICE.4,13 The
increased length of treatment is also likely to result in lower
adherence.
Table IV: NICE guidelines on initial therapy
for peptic ulcer disease4,13
Diagnosis

Treatment

Follow-up

H pylori positive Eradication of H py- Gastric ulcers do an

(duodenal or gastric lori
endoscopy at six to
ulcer)
eight weeks after
treatment.
NSAID use (duodenal Stop NSAID if posor gastric ulcer)
sible.
H pylori positive reFull dose of PPI for peat carbon-13 urea
one to two months.
breath test to check
eradication (ensure
NSAID use and H py- Stop NSAID if pos- acid
suppression
lori positive (duodenal sible.
therapy is stopped for
or gastric ulcer)
Full dose of PPI for
two weeks).
eight weeks.
Continued NSAID use
Eradicate H pylori.
gastroprotection required.

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EVIDENCE BASED PHARMACY PRACTICE

Figure 1: Management flowchart for gastric ulcer

Gastric ulcer

Stop NSAIDs,
if used 1

Full dose PPI for
two months

H pylori positive
Ulcer associated
with NSAID use

H pylori
positive

Eradication
therapy3

H pylori
negative

Endoscopy and
H pylori test4

Full dose PPI for one

or two months

H pylori positive
Ulcer not associated
with NSAID use



Test for
H pylori2

Ulcer healed
H pylori
negative

Low dose treatment as required5

Ulcer not healed

H pylori negative

Healed

Endoscopy4
Not healed

Periodic review 6

1
2
3
4
5
6

16

Refer to specialist
secondary care

Return to self care

Refer to specialist
secondary care

If NSAID continuation is necessary, after ulcer healing offer long term gastric protection or consider substitution to a newer COXselective NSAID.
Use a carbon-13 urea breath test, stool antigen test or, when performance has been validated, laboratory-based serology.
Use a PPI, amoxicillin, clarithromycin 500 mg (PAC500) regimen or a PPI, metronidazole, clarithromycin 250 mg (PMC250) regimen.
Follow guidance found in the British National Formulary for selecting 2nd line therapies.
After two attempts at eradication manage as H pylori negative.
Perform endoscopy 6-8 weeks after treatment. If retesting for H pylori use a carbon-13 urea breath test.
Offer low dose treatment, possibly used on an as required basis, with a limited number of repeat prescriptions.
Review care annually to discuss symptoms, promote stepwise withdrawal of therapy when appropriate and provide lifestyle advice. In
some patients with an inadequate response to therapy it may become appropriate to refer to a specialist.

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EVIDENCE BASED PHARMACY PRACTICE

Figure 2: Management flowchart for duodenal ulcer

Duodenal ulcer

Stop NSAIDs,
if used1

Full dose PPI for
two months

Test positive
Ulcer associated
with NSAID use

Eradication
therapy 3

Test negative

Test positive
Ulcer not associated
with NSAID use

Response

Test for
H pylori2

No response
or relapse

Retest for
H pylori4

Full dose PPI

for one or two
months

Negative

Response

No response

Positive

Eradication
therapy 5

No response
or relapse

2
3
4
5
6
7

No response

Exclude other
causes of DU7

Low dose
treatment as
required 6
Response

Response

Return to self care

Review 8

If NSAID continuation is necessary, after ulcer healing offer long term gastric protection or consider substitution to a newer COXselective NSAID.
Use a carbon-13 urea breath test, stool antigen test or, when performance has been validated, laboratory-based serology.
Use a PPI, amoxicillin, clarithromycin 500 mg (PAC500) regimen or a PPI, metronidazole, clarithromycin 250 mg (PMC250) regimen
Use a carbon-13 urea breath test.
Follow guidance found in the British National Formulary for selecting 2nd line therapies.
Offer low dose treatment, possibly used on an as required basis, with a limited number of repeat prescriptions.
Consider non-compliance with treatment, possible malignancy, failure to detect H pylori infection due to recent PPI or antibiotic
ingestion, inadequate testing, or simple misclassification; surreptitious or inadvertent NSAID or aspirin use; ulceration due to ingestion
of other drugs; Zollinger-Ellison syndrome; Crohns disease.
A small number of patients with chronic, refractory peptic ulceration may require maintenance acid suppression. In some patients with
an inadequate response to therapy it may become appropriate to refer to a specialist for a second opinion.
Review care annually to discuss symptoms, promote stepwise withdrawal of therapy when appropriate and provide lifestyle advice.

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EVIDENCE BASED PHARMACY PRACTICE

Evidence

Eradication of H pylori in duodenal ulcers should be checked

by retesting using a carbon-13 urea breath test. There is a
small risk that gastric ulcers may be malignant, therefore
patients should receive repeat endoscopy and biopsy,
retesting for H pylori six to eight weeks after starting treatment. Acid suppression should be stopped two weeks
before retesting since acid suppression therapy increases
the possibility of false negative results. If a patient remains
positive for H pylori after initial treatment, a regimen that uses
different antibiotics from those used previously should be
chosen. A European consensus report in 20004 suggested a
quadruple drug regimen of a twice daily PPI full dose,
bismuth subsalicylate/subcitrate 120 mg four times daily,
metronidazole 400 mg three times daily, and tetracycline
500 mg four times daily for a minimum of seven days.
Patients on H pylori eradication therapy should be counseled on the importance of completing the course of antibiotics.4 It should also be explained that successful eradication
will reduce the chance of peptic ulcer recurrence. As with
most antibiotics, the most common side effects are gastrointestinal (for example, nausea and diarrhoea). Patients
should avoid alcohol when using regimens that contain
metronidazole, and patients taking the quadruple regimen
should be warned that their tongue and stools may turn black
temporarily as a side effect of the bismuth salt.

NSAID or aspirin use plus H pylori

NSAIDs are usually stopped where possible in patients with
peptic ulcer disease. If H pylori is also found, eradication
therapy is used. However, the role of H pylori eradication in
NSAID-induced ulcers is not clear.4 Eradicating H pylori does
not appear to make a difference to healing rates, whether or
not the NSAID is discontinued. If the NSAID must be continued after ulcer healing, eradication of H pylori is a less
effective secondary prevention strategy than continued acid
suppression with PPIs. There is some evidence that continued presence of H pylori may even be beneficial if NSAIDs
must be continued with gastroprotection. In two studies (the
OMNIUM and ASTRONAUT studies)14,15, patients receiving a
NSAID and omeprazole after ulcer healing had a lower
relapse rate if they were H pylori positive.
The need for gastroprotection in high risk patients on low
dose aspirin is also not clear. The risk of gastrointestinal
bleeding in patients taking 50 mg to 162.5 mg aspirin is
nearly double (odds ratio 1.59), in comparison to a four-fold
increased risk for patients taking NSAIDs.4 It may be sensible
to use gastroprotection. Based on studies, misoprostol and
PPIs are likely to be effective gastroprotective agents.4
NSAID-associated ulcers where NSAIDs cannot be stopped
The most effective strategy for minimising NSAID-induced
ulceration is to limit the use of NSAIDs, encouraging the use of
paracetamol-based analgesia, using NSAIDs for short courses
to manage episodes of acute inflammation, and if NSAIDs must
be used, to use the lowest dose of the safest NSAID (for

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example, ibuprofen 400 mg three times daily). For NSAIDassociated ulcers, NSAIDs should be stopped where
possible, and simple analgesics such as paracetamol with or
without a low dose opioid should be prescribed. Those with
inflammatory diseases, for example rheumatoid arthritis, may
however depend on NSAIDs for effective pain relief.
For prophylaxis, if a NSAID must be used, a concurrent
gastroprotectant should be used or one of the cyclo-oxygenase (COX)-2 selective agents can be considered. When
making this decision, the outcome needs to be considered
whether serious gastrointestinal bleeding can be prevented
and whether symptomatic ulcers can be prevented.
Misoprostol can be used for gastroprotection. A reduction in
serious events has not been demonstrated with PPIs, but
they do reduce the incidence of symptomatic ulcers.4 More
research is, however, needed. H2-antagonists should not be
used for gastroprotection.4 Standard doses have been
shown endoscopically to prevent duodenal ulcers but not
gastric ulcers, while double doses have been shown to
reduce the incidence of endoscopically detected ulcers but
not symptomatic ulcers or serious gastrointestinal complications. In theory, COX-2 inhibitors inhibit the production of
inflammatory prostaglandins while preserving production of
gastroprotective prostaglandins driven by COX-1.4 They can
be used in high risk patients without cardiovascular disease.8
The actual clinical benefit of these drugs has generated
much controversy and the reported increased incidence of
cardiac events fall outside the scope of this article. Therefore, on the basis of cost, safety and tolerability, the PPIs are
most commonly used for gastroprotection. Misoprostol can
also be used, provided the side effects are tolerable. COX-2
inhibitors are an option if the patient is not using aspirin.
For treatment, studies have shown that ulcer healing can be
achieved with PPIs in the continued presence of NSAIDs. The
OMNIUM study14 was a double-blind study, where 935 patients
who required continuous NSAID therapy and who had ulcers or
more than 10 erosions in the stomach or duodenum (or both)
were randomly assigned to receive 20 mg or 40 mg of
omeprazole orally in the morning or 200 g of misoprostol orally
four times daily. The overall rates of successful treatment of
ulcers, erosions, and symptoms associated with NSAIDs were
similar for the two doses of omeprazole and misoprostol.
Maintenance therapy with omeprazole was associated with a
lower rate of relapse than misoprostol. Omeprazole was better
tolerated than misoprostol.
In the ASTRONAUT study15, 541 patients who required
continuous treatment with NSAIDs and who had ulcers or
more than 10 erosions in either the stomach or duodenum
were studied. Patients were randomly assigned to doubleblind treatment with omeprazole, 20 mg or 40 mg orally per
day, or ranitidine, 150 mg orally twice a day, for four or eight
weeks. It was concluded that in patients who use NSAIDs
regularly, omeprazole healed and prevented ulcers more
effectively than did ranitidine.

SA Pharmaceutical Journal January/February 2009

EVIDENCE BASED PHARMACY PRACTICE

Evidence

In the OMNIUM study4,14, 75% of patients were successfully

treated after eight weeks of omeprazole 20 mg. These rates
were comparable to 400 g of misoprostol (71%, a nonsignificant difference). In the ASTRONAUT study4,15, 80% of
patients were successfully treated after eight weeks, superior
to 150 mg twice daily of ranitidine (63%, P=<0.001). Both
studies, however, included patients with endoscopic erosions as well as ulcers. NICE guidelines recommend four to
eight weeks treatment with a PPI, whether or not NSAIDs are
discontinued.12,13

Other ulcers
The prevalence of H pylori is falling with successive birth
cohorts, so ulcers unrelated to H pylori are becoming a
proportionally greater problem.4 These ulcers should heal
with a four to eight week course of PPI, but other aspects
should also be considered, for example failure to detect H
pylori due to recent acid suppression or antibiotic use,
inadvertent NSAID use, other drugs (for example,
biphosphonates or sustained release potassium chloride),
and alternative diagnoses such as Zollinger-Ellison syndrome or Crohns disease.

9.

10.
11.
12.
13.

14.

15.

Hooper L, Brown T, Elliott R, Payne K, Roberts C & Symmons D. 2004.

The Effectiveness of Five Strategies for the Prevention of Gastrointestinal Toxicity induced by Non-steroidal Anti-inflammatory Drugs: Systematic Review. British Medical Journal, 329: 948-952.
Boreham H. 2008. Peptic Ulcer Treatment. Pharmacy Update, 1 (4),
August/September: 29-32.
Standard Treatment Guidelines and Essential Drugs List for South Africa:
Primary Health Care. 2003. Pretoria: The National Department of Health.
British Society of Gastroenterology Endoscopy Committee. 2002. Nonvariceal Upper Gastrointestinal Haemorrhage: Guidelines. Gut, 51: iv1iv6.
North of England Dyspepsia Guideline Development Group. 2004.
Dyspepsia: Managing Dyspepsia in Adults in Primary Care. EvidenceBased Clinical Practice Guideline. Available on the web: http://
www.nice.org.uk/Guidance/CG17/Guidance/pdf/English (date accessed:
25 November 2008).
Hawkey CJ, Karrasch JA, Szczepanski L, Walker DG, Barkun A,
Swannell AJ & Yeomans ND for The Omeprazole versus Misoprostol for
NSAID-Induced Ulcer Management (OMNIUM) Study Group. 1998.
Omeprazole compared with misoprostol for ulcers associated with
nonsteroidal anti-inflammatory drugs. New England Journal of Medicine,
338: 727-734.
Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, Van Rensburg
CJ, Swannell AJ & Hawkey CJ for The Acid Suppression Trial: Ranitidine
versus Omeprazole for NSAID-Associated Ulcer Treatment (ASTRONAUT)
Study Group. 1998. A comparison of omeprazole and ranitidine for
treating and preventing ulcers associated with non-steroidal antiinflammatory drugs (ASTRONAUT Study). New England Journal of
Medicine, 338: 719-726.

Toll-free National HIV

Health Care Worker Hotline

Conclusion

The treatment of peptic ulcer disease generally includes

removal of possible causes of ulceration (for example,
NSAID use or the presence of H pylori), acid suppression
therapy and H pylori eradication therapy. Pharmacists play
an important role in the management of peptic ulcer disease.
They need to ensure that a detailed drug history is taken, in
particular establishing NSAID or aspirin use that may be
contained in over-the-counter products such as cold and flu
preparations. Pharmacists, however, need to know when to
refer and therefore need to be aware of symptoms that
warrant immediate referral.
Advances in the treatment of peptic ulcer disease continue
and pharmacists should ensure that they remain up-to-date
with the latest developments in this field. An extremely
useful reference source for any pharmacist interested to
know more about evidence-based pharmacy practice of
dyspepsia and peptic ulcers is the NICE guideline on
dyspepsia13 that is available at the following website: http://
www.nice.org.uk/Guidance/CG17/Guidance/pdf/English

References:
1.
The Merck Manual of Diagnosis and Therapy. 2006. 18th Edition.
Edited by MH Beers. Whitehouse Station: Merck Research Laboratories.
2.
South African Medicines Formulary (SAMF), 8th Edition. 2008. Edited by
CJ Gibbon. Claremont: Health and Medical Publishing Group of the
South African Medical Association.
3.
Anderson J & Gonzalez J. 2000. H pylori Infection: Review of the
Guideline for Diagnosis and Treatment. Geriatrics, 55 (6): 44-49.
4.
Greer D. 2006. Peptic Ulcer Disease Pharmacological Treatment.
Hospital Pharmacist, 13: 245-250.
5.
Dekker A, Dreyer AC & Smit R. 1993. Pharmacist Initiated Therapy:
Recognition and Treatment of Minor Ailments. Kenwyn: Juta & Co, Ltd.
6.
Rutter P. 2005. Symptoms, Diagnosis and Treatment: A Guide for
Pharmacists and Nurses. Edinburgh: Elsevier Churchill Livingstone.
7.
Rutter P. 2004. Community Pharmacy: Symptoms, Diagnosis and
Treatment. Edinburgh: Churchill Livingstone.
8.
Le TH & Fantry GT. 2008. Peptic Ulcer Disease. eMedicine, 17 July.
Available on the web: http://www.emedicine.com/MED/topic1776.htm
(date accessed: 3 November 2008).

20

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Cape Town provides a toll-free national HIV hotline to all health
care workers in South Africa for patient treatment related
enquiries. The service is free to health care workers.
The toll-free national HIV health care worker hotline provides
information on queries relating to:

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SA Pharmaceutical Journal January/February 2009