C H A P T E R 5 7
Drugs affecting gastrointestinal secretions
901
• Prophylaxis of stress-induced ulcers and acute upper
GI bleeding in critical people (blocking the production
of acid protects the stomach lining, which is at risk
because of decreased mucus production associated
with extreme stress).
• Treatment of erosive gastro-oesophageal reflux
(decreasing the acid being regurgitated into the
oesophagus will promote healing and decrease pain).
• Relief of symptoms of heartburn, acid indigestion and
dyspepsia.
See the Critical thinking scenario for additional infor-
mation on H
2
antagonists.
Pharmacokinetics
Ranitidine is available in oral and parenteral forms.
Nizatidine, cimetidine and famotidine are available only
in oral form. Cimetidine was the first drug in this class to
be developed. It has been associated with antiandrogenic
effects, including gynaecomastia and galactorrhoea. It
reaches peak levels in 1 to 1.5 hours and is metabolised
mainly in the liver; it can slow the metabolism of many
other drugs that use the same metabolising enzyme
system. It is excreted in urine. It has a half-life of 2 hours
and is known to cross the placenta and enter breast milk.
Ranitidine, which is longer acting and more potent
than cimetidine, is not associated with the antian-
drogenic adverse effects or the marked slowing of
metabolism in the liver as cimetidine is. It reaches peak
levels in 5 to 15 minutes when given parenterally and
1 to 3 hours when given orally. It has a duration of 8 to
12 hours and a half-life of 2 to 3 hours. Ranitidine is
metabolised by the liver and excreted in urine. It crosses
the placenta and enters breast milk.
Famotidine is similar to ranitidine, but it is much
more potent than either cimetidine or ranitidine. It
reaches peak effects in 1 to 3 hours and has a duration
of 6 to 15 hours. Famotidine is metabolised in the liver
and excreted in urine with a half-life of 2.5 to 3.5 hours.
Famotidine crosses the placenta and enters breast milk.
Nizatidine, the newest drug in this class, is similar
to ranitidine in its effectiveness and adverse effects. It
differs from the other three drugs in that it is eliminated
by the kidneys, with no first-pass metabolism in the liver.
It is the drug of choice for people with liver dysfunction
and for those who are taking other drugs whose metab-
olism is slowed by the hepatic activity of the other three
H
2
antagonists. It reaches peak effects in 0.5 to 3 hours
and has a half-life of 1 to 2 hours. Like the other three
drugs, it crosses the placenta and enters the breast milk.
Contraindications and cautions
The H
2
antagonists should not be used with known
allergy to any drugs of this class
to prevent hyper-
sensitivity reactions
. Caution should be used during
pregnancy or breastfeeding
because of the potential for
adverse effects on the fetus or breastfeeding infant
and
with hepatic or renal dysfunction,
which could interfere
with drug metabolism and excretion.
(Hepatic dysfunc-
tion is not as much of a problem with nizatidine.) Care
should also be taken if prolonged or continual use of
these drugs is necessary
because they may be masking
serious underlying conditions.
Adverse effects
The adverse effects most commonly associated with
H
2
antagonists include the following: GI effects of
TABLE 57.1
DRUGS IN FOCUS Drugs used to treat gastro-oesophageal reflux disease and ulcer disease (continued)
Drug name
Dosage/route
Usual indications
GI protectant
sucralfate (Carafate,
Ulcyte)
1 g PO b.d to q.i.d.
Short-term treatment of duodenal ulcers;
maintenance of duodenal ulcers (at
reduced dose) after healing in adults;
treatment of oral and oesophageal
ulcers due to radiation, chemotherapy
or sclerotherapy; currently under
investigation for treatment of gastric
ulcers, gastric damage induced by
non-steroidal antiinflammatory drugs
(NSAIDs), prevention of stress ulcers in
acutely ill individuals
Prostaglandin
misoprostol (Cytotec)
200 mcg PO q.i.d.; reduce dose in people with
renal impairment
Prevention of NSAID-induced ulcers in
adults at high risk for development of
these gastric ulcers; under investigation
for treatment of duodenal ulcers in
people who are not responsive to H
2
antagonists; used in combination therapy
with mifepristone as an abortifacient
