Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 11 GLUCOCORTICOSTEROIDS AND ANTIHISTAMINES
Pharmacokinetics
The pharmacokinetics of antihistamines in the dog and
cat are largely unknown but following oral administration,
these drugs are rapidly absorbed, achieving peak
plasma levels within 1 h. Metabolism generally occurs
in the liver and excretion is via the urine. Antihistamines
may cross the placenta and be secreted in milk. A recent
study has reported the pharmacokinetics of clemastine
in the dog. After oral administration (0.5 mg/kg),
the bioavailability was 3% and the drug was unable
to inhibit wheal formation after intradermal injection
of histamine. By contrast, intravenous administration
(0.1 mg/kg) inhibited wheal formation for up to 7 h post
injection. The results of this study suggest that oral
clemastine administered at currently recommended dose
rates (see above) is unlikely to be an effective therapy.
Similar studies are required for other antihistamines
used in companion animals.
Adverse effects
● H 1 -blockers may induce a wide range of adverse
effects, which vary with the drug used and the individual
patient; however, these are generally mild and
do not warrant discontinuation of therapy.
● Depending upon the drug used, some form of adverse
effect was recorded in 0–25% of treated dogs in
published studies.
● The most commonly recognized adverse effect is
CNS depression (lethargy, depression, drowsiness,
somnolence), which has been recorded in dogs
given amitriptyline, chlorphenamine (chlorpheniramine),
clemastine, diphenhydramine, hydroxyzine,
terfenadine or alimemazine (trimeprazine). This
depression may spontaneously resolve after 3–7
days, even in the face of continued antihistamine
administration.
● Less common side effects include the following.
– Excitement (restlessness, nervousness, tremors,
hyperactivity), due to reduced seizure threshold,
has been reported in dogs given cyproheptadine,
doxepin, hydroxyzine or terfenadine.
– Gastrointestinal effects (anorexia, vomiting, diarrhea,
constipation) are recorded in dogs treated
with amitriptyline, chlorphenamine (chlorpheniramine),
clemastine, diphenhydramine, doxepin,
hydroxyzine or terfenadine. These effects may
sometimes be prevented if the drugs are given
with food.
– Anticholinergic effects (dry mouth, throat, nose
and eyes; urinary retention or dysuria; intestinal
atony) have been recorded in dogs given chlorphenamine
(chlorpheniramine) or clemastine.
– An increase in pruritus has occasionally been recognized
in dogs treated with chlorphenamine
(chlorpheniramine), diphenhydramine, hydroxyzine
or terfenadine. This may occur more frequently
with higher dosages of the drugs.
– Cardiovascular effects (tachycardia, arrhythmia,
hypertension) have been reported after overdosing
with some antihistamines.
● Similar adverse effects have been recorded in
10–40% of cats treated with antipruritic doses of
H 1 -blockers. These include:
– drowsiness (with chlorphenamine
(chlorpheniramine))
– diarrhea (with clemastine)
– polyphagia, sedation, increased vocalization and
vomiting (with cyproheptadine).
Known drug interactions
● H 1 -blocking antihistamines are reported to act synergistically
with products containing ω-6/ω-3 fatty
acids in the control of pruritus in the dog and cat,
and have also been administered concurrently with
glucocorticoids, enabling a reduced dosage of glucocorticoid
to be used.
● Contraindications include the concurrent administration
of monoamine oxidase inhibitors (e.g.
amitraz), which may potentiate the anticholinergic
effects of these antihistamines, or coadministration
of other CNS depressant agents (e.g. barbiturates,
narcotics, anesthetics), which may cause additive
CNS depression.
● Antihistamines may partially counteract the anticoagulative
effects of histamine or warfarin.
● Astemizole or terfenadine should not be coadministered
with ketoconazole, itraconazole, fluconazole,
clarithromycin or erythromycin, as these drugs
may increase the plasma levels of the antihistamine
by inhibiting metabolism, and enhance the potential
for the antihistamine to induce cardiac arrhythmia
(reported in humans but not in dogs).
● The phenothiazine antihistamines should not be administered
with quinidine, antidiarrheal mixtures (e.g.
kaolin/pectin), antacids or adrenaline (epinephrine).
● Doxylamine, diphenhydramine or pyrilamine may
also enhance the effects of adrenaline.
Contraindications and precautions
● Antihistamines are not recommended for animals
with hepatic or cardiovascular disease, hypertension,
glaucoma, hyperthyroidism or a history of seizures,
urinary retention or intestinal atony.
● There is no information on the safety of administration
during pregnancy or potential effects of transfer
in the milk. Antihistamine therapy should be withdrawn
before performing intradermal skin testing for
allergy.
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