Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 3 ADVERSE DRUG REACTIONS
Hemoglobin
Another species difference which may raise the risk of
adverse reactions in cats compared to dogs is the
increased susceptibility of feline hemoglobin to oxidation
and therefore methemoglobinemia. There are a
number of proposed mechanisms postulated to explain
this, including the different structure of feline hemoglobin,
lower concentrations or activities of intracellular
repair enzyme and differences in intracellular concentrations
of glutathione-conjugating enzymes. Drugs affecting
oxidative processes include the sulfonamides,
nitrofurans and sulfones.
Receptors
Differences between dogs and cats with respect to drug
receptor distribution and affinity have been described,
with morphine representing the archetypal example. In
addition to a slower rate of biotransformation due to
the deficiency of glucuronidation in the cat, differences
observed in the pharmacodynamic effects of morphine
in the cat compared to the dog include CNS stimulation
(CNS depression in the dog), centrally mediated emesis
at much reduced sensitivity of the cat compared to the
dog (dog requires dose 1/740 that of cat) and pupillary
dilation (miosis in the dog). However, at a dose rate of
0.1 mg/kg subcutaneously (compared with 0.1–2 mg/kg
in the dog), morphine provides effective analgesia in
the cat.
Various receptors in the vomiting center, the chemoreceptor
trigger zone (CRTZ), the vestibular pathways
and the periphery (e.g. gut) are involved in the vomiting
reflex. Species differ in the relative importance of some
neurotransmitter–receptor systems related to vomiting
and this has an impact on the efficacy of antiemetics.
For example, apomorphine, a D 2 -dopamine receptor
agonist, is a potent emetic agent in dog and man but
not in cat, monkey, pig, horse or domestic fowl. This
suggests that D 2 -dopamine receptor antagonists such as
metoclopramide might not be very useful as antiemetic
agents in the cat.
In contrast, xylazine, an α 2 -adrenergic agonist, is a
more potent emetic agent in the cat than the dog, suggesting
that α 2 -adrenergic antagonists, e.g. prochlorperazine
(Stemetil), might be more useful antiemetic
agents than D 2 -dopamine receptor antagonists. Cytotoxic
drug-induced emesis has been shown to be mediated
by 5-HT 3 receptors in the CRTZ of the cat in
contrast to the dog where visceral and vagal afferent
5-HT 3 receptors are activated.
Histamine receptors have not been demonstrated in
the CRTZ of the cat. Studies based on eliminating the
emetic response to parenterally administered compounds
by lesioning the CRTZ suggest that the CRTZ may be
less sensitive to emetic compounds in the cat than in the
dog. Alternatively, other sites for the origin of emesis
may be more sensitive in the cat than the dog.
Other drug effects
Other examples of drugs which have different effects in
cats compared to dogs include febantel (which induces
emesis much more readily in cats than dogs) and digitalis
glycosides (the cat is less tolerant than the dog,
presumably because of increased sensitivity of feline
cardiac Na + ,K + -ATPase to inhibition). Cats are more
susceptible to aminoglycoside neurotoxicity than other
species.
Behavioral differences
The grooming behavior of cats increases the likelihood
that topically applied medications will be ingested.
Advantage can be taken of this behavior by applying
medications intended for ingestion to accessible parts of
the cat’s body (for example, anthelmintic or antibiotic
paste preparations). However, cats are at greater risk
of exposure to purposefully or adventitiously applied
topical toxicants such as disinfectants (particularly phenolics
that are principally candidates for glucuronidation)
or pesticides. Indeed, concentrated preparations of
permethrin applied topically to cats can be lethal when
ingested.
Drugs which should not be used or used cautiously
in cats and those which have a different toxicity profile
to dogs are listed in Tables 3.2 and 3.3.
Table 3.2 Drugs not recommended for use in cats
Acetominophen
(paracetamol)
Apomorphine
Azathioprine
Benzocaine
Cisplatin
Propylthiouracil
Phenytoin
Scopolamine
Sodium phosphate
enemas
Permethrin (high
concentration
products)
Methemoglobinemia and Heinz body
anemia
Significant CNS depression
Bone marrow suppression
Methemoglobinemia
Laryngeal edema
Fatal, acute pulmonary edema
Lethargy
Weakness
Anorexia
Bleeding diathesis
Sedation
Ataxia
Anorexia
Dermal atrophy
Tendency to cause behavioral changes
Depression
Ataxia
Vomiting
Bloody diarrhea
Hyperesthesia, generalized tremors,
muscle fasciculations, hyperthermia,
seizures, death
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