Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CLASSES OF ANTIEMETICS
wide margin of safety for the drug suggests that this
may not have clinically relevant adverse effects.
5-HT 3 antagonists
EXAMPLES
Ondansetron (Zofran®), granisetron (Kytril®), dolasetron
(Carpuject®, Anzemet®, Anemet®, Zamanon®) and
tropisetron
Clinical applications
The 5-HT 3 receptor antagonists are extremely potent
(and expensive) antiemetics used in the management of
cancer therapy-induced emesis in humans. Their clinical
efficacy is orders of magnitude better than metoclopramide
(e.g. 100 times better in the ferret) and they are
often used in cases when ‘first-line’ antiemetics (e.g.
metoclopramide or chlorpromazine) are ineffective. In
this regard, these drugs can often control vomiting in
puppies with parvoviral gastroenteritis. They have been
used occasionally in dogs to control cisplatin-induced
emesis but cost is prohibitive for most veterinary clinical
situations.
Mechanism of action
5-HT 3 receptors are located in the CTZ and, peripherally,
on vagal nerve terminals and on enteric neurones
in the gastrointestinal tract. Although initially 5-HT 3
antagonists were thought to have a central action on the
CTZ, recent work suggests that their main effect is
through antagonism of peripheral 5-HT 3 receptors in
the gut. This is supported by work demonstrating that
chemotherapy-induced vomiting is caused by serotonin
release from small intestinal enterochromaffin cells.
Formulations and dose rates
Most veterinary experience has been with ondansetron; most of the
other drugs have not had extensive use at the current time. No
veterinary formulations of any of these drugs are available.
ONDANSETRON
Ondansetron is available both as injectable and as tablet
formulations.
DOGS
Prevention of cisplatin-induced vomiting
• 0.5 mg/kg IV as a loading dose and then 0.5 mg/kg/h as an
infusion for 6 h
• 0.1 mg/kg PO q.12–24 h or at 30 min prior to and 90 min after
cisplatin infusion
For intractable vomiting, when first-line drugs are ineffective
• 0.1–0.176 mg/kg q.6–12 h as a slow intravenous push
• 0.5–1.0 mg/kg PO once or twice daily
CATS
The use of ondansetron in cats is controversial and many pharmacologists
do not recommend its use in this species.
OTHER 5-HT 3 ANTAGONISTS
Dolasetron is also available as both injectable (0.625 mL ampoules)
and tablet (50 mg and 100 mg strength) formulations. The size of
tablets is inconvenient for most cats and dogs, such that oral ondansetron
preparations are preferred.
• 0.5–0.6 mg/kg IV, SC or PO q.24 h
Adverse effects
● Experimental studies suggest that 5-HT 3 antagonists
are very safe in animals, showing minimal toxicity at
doses up to 30 times greater than those needed to
abolish vomiting.
● Given that ondansetron, and related products, are
potent antiemetics, their use may mask signs of ileus
or gastrointestinal distension. These drugs should be
used with caution in cases where gastrointestinal
obstruction cannot be excluded because appropriate
therapy may be delayed.
● In humans, constipation, headaches, occasional
alterations in liver enzymes and rarely hypersensitivity
reactions have been reported.
● Dolasetron has also been associated with ECG interval
prolongation (of the P-R, Q-T and J-T segments),
whilst arrhythmias and hypotension have also been
reported for ondansetron.
● Safety of this drug group during gestation has not
been clearly established, so the drug should be used
with caution in pregnant animals.
● Ondansetron is a potential substrate of P-glycoprotein.
Given that some rough collies have a mutation
causing a nonfunctional protein, these dogs and
associated breeds may be more sensitive to the effects
of 5-HT 3 antagonists.
Anticholinergics
EXAMPLES
Atropine, butylscopolamine (hyoscine), propantheline,
isopropamide
Clinical applications
Anticholinergics are mainly used for their antispasmodic
and antisecretory actions for some types of diarrhea.
Given that their use is contradicted in many
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