A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

PEPTIC ULCERATION 249
• With regard to drug therapy, several drugs (see below) are
effective. Documented duodenal or gastric ulcerations
should be treated with an H 2 -blocker or proton-pump
inhibitor.
• Test for the presence of H. pylori by using the urease CLO
test or antral biopsy at endoscopy.
• All suspected gastric ulcers should be endoscoped and
biopsied to exclude malignancy, with repeat endoscopy
following treatment, to confirm healing and for repeat
biopsy.
• The current recommendation in relation to H. pylori is
summarized above.
Key points
General management of peptic ulceration
• Stop smoking.
• Avoid ulcerogenic drugs (e.g. NSAIDs, alcohol,
glucocorticosteroids).
• Reduce caffeine intake.
• Diet should be healthy (avoid obesity, and foods that
give rise to symptoms).
• Test for the presence of H. pylori.
The choice of regimen used to eradicate H. pylori is
based on achieving a balance between efficacy, adverse effects,
compliance and cost. Most regimens include a combination
of acid suppression and effective doses of two antibiotics.
A typical regime for eradication of H. pylori is shown in
Table 34.1.
Eradication should be confirmed, preferably by urea breath
test at a minimum of four weeks post-treatment.
Non-steroidal anti-inflammatory
drug-associated ulcer
NSAID-related ulcers will usually heal if the NSAID is withdrawn
and a proton-pump inhibitor is prescribed for four
weeks. If the NSAID has to be restarted (preferably after healing),
H 2 -receptor antagonists or proton-pump inhibitors or
misoprostol (see below) should be co-prescribed. If H. pylori is
present it should be eradicated.
Key points
Ulcer-healing drugs
Reduction of acidity:
• antacids;
• H 2 -blockers;
• proton-pump inhibitors;
• muscarinic blockers (pirenzapine).
Mucosal protection:
• misoprostol (also reduces gastric acid secretion);
• bismuth chelate (also toxic to H. pylori);
• sucralfate;
• carbenoxolone (rarely prescribed).
Table 34.1: Typical triple therapy Helicobacter pylori eradication regime
Lansoprazole
30 mg bd
}
Amoxicillin a 1 g bd all for 1 week
Clarithromycin
500 mg bd
a Metronidazole 400 mg bd if patient is allergic to penicillin.
DRUGS USED TO TREAT PEPTIC ULCERATION BY
REDUCING ACIDITY
ANTACIDS
Use and adverse effects
Antacids have a number of actions which include neutralizing
gastric acid and thus relieving associated pain and nausea,
reducing delivery of acid into the duodenum following a
meal, and inactivation of the proteolytic enzyme pepsin by
raising the gastric pH above 4–5. In addition, it is thought that
antacid may increase lower oesophageal sphincter tone and
reduce oesophageal pressure.
A number of preparations are available and the choice will
depend on the patient’s preference, often determined by the
effect on bowel habit (see Table 34.2).
In general terms, antacids should be taken approximately
one hour before or after food, as this maximizes the contact
time with stomach acid and allows the antacid to coat the
stomach in the absence of food.
Drug interactions
Magnesium and aluminium salts can bind other drugs in the
stomach, reducing the rate and extent of absorption of antibacterial
agents such as erythromycin, ciprofloxacin, isoniazid,
norfloxacin, ofloxacin, pivampicillin, rifampicin and
most tetracyclines, as well as other drugs such as phenytoin,
itraconazole, ketoconazole, chloroquine, hydroxychloroquine,
phenothiazines, iron and penicillamine. They increase
the excretion of aspirin (in alkaline urine).
H 2 -RECEPTOR ANTAGONISTS
H 2 -receptors stimulate gastric acid secretion and are also
present in human heart, blood vessels and uterus (and probably
brain). There are a number of competitive H 2 -receptor
antagonists in clinical use, which include cimetidine and
ranitidine. The uses of these are similar and will be considered
together in this section. Because each drug is so
widely prescribed, separate sections on their individual
adverse effects, pharmacokinetics and interactions are given
below, followed by a brief consideration of the choice
between them.
Use
1. H 2 -receptor angonists are effective in healing both gastric
and duodenal ulcers. A four-week course is usually