Page 409 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

376 SECTION | IV Drugs of Use and Abuse

VetBooks.ir used as antiemetics to treat motion sickness. Doxylamine is TABLE 21.3 Antihistamines (H 1 Histamine Receptor
used as a sedative in sleep aids. Hydroxyzine is used by
Inhibitors) See Gwaltney-Brant (2006) for more
veterinarians to treat canine atopy (Tegzes et al., 2002).
Malicious poisoning with diphenhydramine has been detailed information
reported in a dog (Buchweitz et al., 2014).
First Generation Second Generation
Toxicity Alkylamines Piperadines
Brompheniramine Terfenadine
An incomplete list of antihistamines is provided in
Table 21.3. Chlorpheniramine is the antihistamine most Chlorpheniramine Astemizole
commonly associated with adverse effects in dogs (Papich, Dexbrompheniramine Levocabastine
1990; Gwaltney-Brant, 2004). The IV LD 50 for diphenhy-
Dexchlorpheniramine Loratadine
dramine is 24 30 mg/kg in dogs, and the human mini-
mum oral lethal dose is about 10 mg/kg. The oral LD 50 for Dimetindene
clemastine in dogs is 175 mg/kg. The therapeutic dose Pheniramine Third Generation
for hydroxyzine is 2.2 mg/kg, and 111 mg/kg is reported
Triprolidine Desloratadine
as toxic in dogs (Tegzes et al., 2002). Terfenadine, which
is no longer sold in the United States, caused clinical Ethanolamines Fexofenadine
signs of toxicosis in a dog at a dose of 6.6 mg/kg Clemastine Levocetirizine
(Otto and Greentree, 1994; Gwaltney-Brant, 2004). Dimenhydrinate
Electroencephalogram changes were noted in dogs dosed
Diphenhydramine
with 30 mg terfenadine/kg, clinical signs were noted in
dogs given in 100 mg/kg/day for 2 3 weeks, and vomiting Bromodiphenhydramine
was a consistent finding in dogs dosed with 150 mg/kg. Carbinoxamine

Doxylamine
Pharmacokinetics
Phenyltoloxamine
Antihistamines are well-absorbed by the monogastric gas-
Ethylenediamines
trointestinal tract, but oral doses are poorly absorbed in
ruminants (Adams, 2001; Gwaltney-Brant, 2004). The Antazoline
anticholinergic effects of antihistamines can slow absorp- Pyrilamine
tion by delaying gastric emptying. Peak plasma concentra-
Tripelennamine
tions usually occur within 2 4 h of ingestion, and the
onset of clinical effects tends to be 20 45 min after inges- Phenothiazines
tion. Therapeutic effects usually last from 3 to 12 h. Methdilazine
Antihistamines are highly protein-bound. First-generation Trimeprazine
antihistamines freely cross the BBB, and are more likely
Piperazines
to cause CNS effects than second-generation products,
which do not normally enter the CNS, unless given at very Hydroxyzine
high doses. Terfenadine has been detected in cerebrospinal Cyproheptadine
fluid in overdose situations (Otto and Greentree, 1994).
Meclozine
Metabolism of antihistamines takes place predomi-
nantly in the liver, and there can be significant first-pass Cyclizine
effect. Only 40% 60% of diphenhydramine enters the Buclizine
general circulation from the portal circulation in humans.
Chlorcyclizine
Hydroxyzine is metabolized to the active product cetiri-
zine, which does not cross the BBB. The elimination half- Niaprazine
life of antihistamines is dependent upon the individual Certirizine
compound. Most metabolites are excreted in the urine, Tricyclics
although there is some biliary excretion of terfenadine.
Promethazine
Antihistamines excreted into the bile can undergo entero-
hepatic cycling.