patients intolerant of or refractory
to first-line agents and they may
have some place as salvage agents
for patients with breakthrough
emesis.
Before the introduction of
5-HT3 RAs, dopamine receptor
antagonists were an essential part
of antiemetic therapy in CINV.
Metoclopramide, introduced in
1981, is a substituted benzamide
dopamine antagonist, causing
central and peripheral dopamine
D2 antagonism at low doses.
Before the introduction of 5-HT3
RAs, metoclopramide was thought
to be one of the most
effective single agents
for prevention of
emesis in CINV.
Although it was
part of former
international
guidelines,
its use is not
recommended
anymore for
prevention of acute
CINV. However, it
has proven efficacy in the
prevention of delayed CINV. 1,3,47
The use of metoclopramide is
related to the risk of irreversible
tardive dyskinesia with higher
doses and long-term use and a
special alert due to its association
with extrapyramidal symptoms in
children. 47
Domperidone is a selective
peripheral dopamine (D2)
antagonist, less likely to cross the
blood–brain barrier than other
agents, and thus is less prone to,
but not free from, extrapyramidal
reactions. Administration of these
drugs to children and young
adolescents as first-line treatment
is not recommended. 1,3 Its use is
not mentioned anymore in current
guidelines. 6,7,9 Alizapride has shown
to be inferior to metoclopramide
when given as monotherapy,
or in combination with a
corticosteroid or benzodiazepine.
It might be effective in managing
breakthrough CINV in patients
already treated with a 5-HT3 RA
and a corticosteroid.
The most common
adverse effect is
drowsiness and
its use has been
associated with
extrapyramidal
symptoms. 1,3,48
Phenothiazines
act predominantly
by antagonising
dopaminergic
receptors (D2) involved
in emesis. All phenothiazines
(chlorpromazine, perphenazine)
have antiemetic properties,
although the relative efficacy of
these agents remains unclear. Main
adverse effects are extrapyramidal
reactions such as dystonia and,
with prolonged use, tardive
dyskinesia. 3
Butyrophenones (haloperidol,
droperidol) are major tranquilisers
that have an antiemetic effect
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