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P A R T 1 1
Drugs acting on the gastrointestinal system
P
henothiazines
The two
phenothiazines
most commonly used as
antiemetics are prochlorperazine (
Stemetil
) and pro-
methazine (
Phenergan
), both of which have rapid onset
and limited adverse effects. Other drugs in this group
include chlorpromazine (
Largactil
). Chapter 22 dis-
cusses the phenothiazines in greater detail. (
See the
Critical thinking scenario for additional information
about caring for a person taking prochlorperazine
.)
Therapeutic actions and indications
Phenothiazines are centrally acting antiemetics that
change the responsiveness or stimulation of the CTZ in
the medulla (Figure 59.1). The phenothiazines are rec-
ommended for the treatment of nausea and vomiting,
including that specifically associated with anaesthesia;
severe vomiting; and
intractable hiccoughs
, which occur
with repetitive stimulation of the diaphragm and lead
to persistent diaphragm spasm. See Table 59.1 for usual
indications for each of these agents.
Pharmacokinetics
These drugs are available as tablets or as syrup for oral
administration, as rectal suppositories and as solution
for intramuscular (IM) or intravenous (IV) use. Route
of choice is determined by the condition of the person.
They have a rapid onset of action of 5 to 20 minutes and
duration of action of 3 to 12 hours, depending on route
of administration. They are metabolised in the liver
and excreted in the urine. They are known to cross the
placenta and enter breast milk.
Contraindications and cautions
In general, antiemetics should not be used in people with
coma or severe central nervous system (CNS) depres-
sion or in those who have experienced brain damage or
injury
because of the risk of further CNS depression.
Other contraindications include severe hypotension or
hypertension and severe liver dysfunction,
which might
interfere with the metabolism of the drug.
Caution
should be used in individuals with renal dysfunction,
moderate liver impairment, active peptic ulcer or during
pregnancy and breastfeeding
because of the potential
for adverse effects on the fetus or baby
. See Chapter 22
for details about the phenothiazines.
Adverse effects
Adverse effects associated with antiemetics are linked
to their interference with normal CNS stimulation or
TABLE 59.1
DRUGS IN FOCUS Antiemetic agents (continued)
Drug name
Dosage/route
Usual indications
5-HT
3
receptor blockers (continued)
granisetron (Kytril)
Adult and paediatric (>2 years): 10 mcg/kg IV
over 5 mins starting within 30 minutes of
chemotherapy; or 1 mg PO b.d. beginning up
to 1 hour before chemotherapy and giving the
second dose 12 hours after, use only on days
of chemotherapy
Treatment of nausea and vomiting
associated with emetogenic
chemotherapy
ondansetron (Zilfojim,
Zofran)
Adult: 8 mg b.d. before chemotherapy, then
8 mg b.d.
Paediatric (4–12 years): 4 mg PO t.d.s.; use
same IV dose as adults
Treatment of severe nausea and
vomiting associated with emetogenic
chemotherapy, radiation therapy,
postoperative situations
palonosetron (Aloxi)
0.25 mg IV as a single dose over 30 seconds
given 30 minutes before the start of
chemotherapy; do not repeat dose for 7 days
Treatment of acute and delayed vomiting
associated with highly emetogenic
chemotherapy
tropisetron (Navoban)
Adult: 5 mg/day for 6 days
Treatment of severe nausea and
vomiting associated with emetogenic
chemotherapy, radiation therapy,
postoperative situations
Substance P/neurokinin 1 receptor antagonists
aprepitant (Emend)
125 mg PO 1 hour before chemotherapy
(day 1); then 80 mg PO in the morning, on
days 2 and 3, with dexamethasone 12 mg
PO on day 1 and 8 mg PO on days 2–4, and
32 mg ondansetron IV on day 1 only
Prevention of acute and delayed nausea
and vomiting associated with highly
emetogenic cancer chemotherapy
fosaprepitant (Emend IV )
Adult 115 mg IV 30 minutes before
chemotherapy
Prevention of acute and delayed nausea
and vomiting associated with highly
emetogenic cancer chemotherapy
