with ondansetron, granisetron
and tropisetron and, recently,
palonosetron. 17–19
Second-generation 5-HT 3 RAs
Palonosetron is structurally
unrelated to other available 5-HT 3
RAs. It differs in having 30–100-
fold higher affinity for the 5-HT 3
receptor and has a significantly
longer half-life (40 hours)
compared with first-generation
5-HT 3 antagonists (ondansetron:
children <15 years: 2–7 hours;
adults: 3–6 hours; granisetron:
oral 6 hours; intravenously
9 hours; dolasetron: ≤10 min;
hydrodolasetron: adults: 6–8 hours;
children: 4–6 hours; tropisetron:
8 hours). 1,3,18,19
Clinical trials have
demonstrated the non-inferiority
and superiority of palonosetron
versus first generation 5-HT 3
RAs. 20,21
Palonosetron is also indicated in
paediatric patients ≥1 month up to
17 years of age for the prevention
of acute nausea and vomiting
associated with initial and repeat
courses of emetogenic cancer
chemotherapy, including HEC. 19
The safety of palonosetron is
similar to other currently available
5-HT 3 RAs. Common adverse events
include headache, constipation,
fever, abdominal pain, diarrhoea,
pruritus, pain, asthenia and
insomnia. As with other 5-HT 3 RAs,
caution should be exercised in the
concomitant use of palonosetron
with medicinal products that
increase the QT interval, or in
patients who have, or are likely
to develop, prolongation of the
QT interval. 1,3,19 Palonosetron is
the only 5-HT 3 RA that does not
prolong QT interval in a clinically
significant way. 22
Palonosetron and granisetron
subcutaneous extended release
injection are the preferred 5-HT 3
RAs for delayed nausea and
prevention in MEC. 7
Neurokinin-1 (NK 1 ) RAs
Substance P, an 11-amino acid
neuropeptide, is the endogenous
ligand for the NK 1 receptor. NK 1
RAs represent the newest class
of antiemetic agents effective for
the prevention of CINV and have
significantly improved the rate of
complete response in the overall,
acute and delayed phases.
Substance P is a neuropeptide
from the family of tachykinins
that is abundantly and widely
distributed in the central nervous
system and other tissues. NK 1
receptors are localised in the
brainstem nuclei and the dorsal
vagal complex, regions of the brain
involved in the regulation process
of emesis. Substance P itself is able
to induce emesis.
The signals of substance P
are mediated through the NK 1
receptor, classified as a G-protein-
coupled receptor, that is associated
to the inositol phosphate signal
transduction pathway. 1,3,7,23–27
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