C H A P T E R 5 7
Drugs affecting gastrointestinal secretions
907
of erosive oesophagitis and ulcers; and in combination
with amoxycillin and clarithromycin for the treatment
of
H. pylori
infection. See Table 57.1 for usual indica-
tions for each of these agents.
Pharmacokinetics
Esomeprazole, omeprazole and pantoprazole are availa-
ble in oral forms and as IV preparations. Lansoprazole
and rabeprazole are available only in delayed-release
oral forms.
These drugs are acid labile and are rapidly absorbed
from the GI tract, reaching peak levels in 3 to 5 hours.
They undergo extensive metabolism in the liver and are
excreted in urine. Omeprazole is faster acting and more
quickly excreted than the other proton pump inhibitors.
It has a half-life of 30 to 60 minutes. Esomeprazole is a
longer-acting drug; it has a half-life of 60 to 90 minutes
and a duration of 17 hours. It is not broken down as
rapidly in the liver as the parent drug omeprazole. Lan-
soprazole has a half-life of 2 hours and duration of
12 hours.
Pantoprazole and rabeprazole have half-lives of
90 minutes and durations of 12 to 14 hours. There are
no adequate studies about whether these drugs cross the
placenta or enter breast milk.
Contraindications and cautions
These drugs are contraindicated in the presence of
known allergy to either the drug or the drug compo-
nents
to prevent hypersensitivity reactions
. Caution
should be used in pregnant or breastfeeding women
because of the potential for adverse effects on the fetus
or neonate
. The safety and efficacy of these drugs have
not been established for people younger than 18 years of
age, except for lansoprazole, which is the proton pump
inhibitor of choice if one is needed for a child.
Monitoring of serum magnesium levels prior to and
during treatment should be considered for:
•
people expected to require long-term PPI treatment.
•
people who take other medicines such as digoxin or
medicines that may cause hypomagnesaemia (such as
diuretics).
Adverse effects
The adverse effects associated with these drugs are
related to their effects on the H
+
, K
+
-ATPase pump on
the parietal and other cells. CNS effects of dizziness and
headache are commonly seen; asthenia (loss of strength),
vertigo, insomnia, apathy and dream abnormalities
may also be observed. GI effects can include diar-
rhoea, abdominal pain, nausea, vomiting, dry mouth
and tongue atrophy. Upper respiratory tract symptoms,
including cough, stuffy nose, hoarseness and epistaxis,
are frequently seen. Other, less common adverse effects
include rash, alopecia, pruritus, dry skin, back pain and
fever. In preclinical studies, long-term effects of proton
pump inhibitors included the development of gastric
cancer. Recent studies show an increase in bone loss in
people using these drugs long term.
Clinically important drug–drug interactions
There is a risk of increased serum levels and increased
toxicity of benzodiazepines, phenytoin and warfarin if
these are combined with these drugs; people should be
monitored closely. Decreased levels of ketoconazole and
theophylline have been reported when combined with
these drugs, leading to loss of effectiveness. Sucralfate
is not absorbed well in the presence of these drugs, and
doses should be spaced at least 30 minutes apart if this
combination is used.
Prototype summary: Omeprazole
Indications:
Short-term treatment of active duodenal
ulcer or active benign gastric ulcer; treatment of
heartburn or symptoms of gastro-oesophageal
reflux; treatment of pathological hypersecretory
syndromes; eradication of
H. pylori
infection as
part of combination therapy.
Actions:
Specifically inhibits the hydrogen–
potassium adenosine triphosphatase enzyme system
on the secretory surface of the gastric parietal
cells, blocking the final step in acid production and
decreasing gastric acid levels.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
0.5–3.5 hours
Varies
T
1/2
:
30 to 60 min; metabolised in the liver and
excreted in urine and bile.
Adverse effects:
Headache, dizziness, vertigo,
insomnia, rash, diarrhoea, abdominal pain, nausea,
vomiting, upper respiratory infection symptoms,
cough.
Care considerations for
people receiving proton pump inhibitors
Assessment: History and examination
■
■
Assess for
possible contraindications or cautions
:
history of allergy to a proton pump inhibitor
to
reduce the risk of hypersensitivity reaction
; current
status of pregnancy or breastfeeding
because of the
potential for adverse effects on the fetus or infant
.
■
■
Perform a physical examination to establish
baseline data before beginning therapy
