Antihistamines are H1-receptor
antagonists that provide symptomatic relief of allergic signs caused by
histamine release, including pruritus and anaphylactic reactions. They are also
used as sedatives and antiemetics. Antihistamines belong to different classes
and are categorized as first- or second-generation (also called nonsedating)
antihistamines. First-generation antihistamines may cause adverse effects
because of their cholinergic activity and ability to cross the blood-brain
barrier. Second-generation antihistamines are more lipophobic than
first-generation antihistamines and are thought to lack CNS and cholinergic
effects at therapeutic doses. Antihistamines are often found in combination with
other ingredients (eg, decongestants, analgesics like acetaminophen or NSAIDs)
in many OTC cold, sinus, and allergy medications.
Chlorpheniramine is a first-generation propylamine-derivative
antihistamine. Oral absorption of chlorpheniramine in dogs is rapid and
complete, reaching peak plasma concentrations in 30–60 min. Chlorpheniramine
maleate undergoes substantial first-pass effect. Chlorpheniramine and
its metabolites are primarily excreted in urine. The recommended dose in cats
and dogs is 1–2 mg and 2–8 mg respectively, PO, bid-tid. Mild clinical signs
such as depression and GI upset have been reported for dosages <1 mg/kg.
Significant clinical signs such as ataxia, tremors, depression or hyperactivity,
hyperthermia, and seizures may be seen within 6 hr of ingestion of large
Clemestine, because of its low oral bioavailability in dogs (3% vs
20%–70% in people), may have limited effectiveness at the recommended dosages of
0.05–0.1 mg/kg, PO, bid; 1.34 mg of clemestine fumerate is equivalent to 1 mg of
clemestine. Common adverse effects of clemestine may include sedation, lethargy,
and anticholinergic signs (dry mouth, tachycardia, agitation, decreased
Dimenhydrinate and diphenhydramine
are first-generation ethanolamine-derivative antihistamines. Dimenhydrinate is
used for its antiemetic effects and for prevention of motion sickness in dogs
and cats. Diphenhydramine is well absorbed orally in people but undergoes
first-pass metabolism in the liver with only 40%–60% of the drug reaching the
systemic circulation. Peak plasma concentrations of ethanolamine-derivative
antihistamines occur within 1–5 hr; elimination half-lives vary from 2.4–10 hr.
A recommended dosage of dimenhydrinate and diphenhydramine in cats and dogs is
4–8 mg/kg and 2–4 mg/kg, respectively. Hyperactivity or depression,
hypersalivation, tachypnea, and tachycardia are the most common adverse effects
reported with these antihistamines, generally within 1 hr of exposure.
Promethazine hydrochloride is an ethylamino derivative of
phenothiazine and first-generation antihistamine used to manage motion sickness.
Promethazine is widely distributed in body tissues and readily crosses the
placenta. Overdoses may result in CNS depression or excitation. CNS depression
was reported in a dog 30 min after ingesting promethazine at 1 mg/kg.
Meclizine is a first-generation piperazine-derivative antihistamine
commonly used as an antiemetic. Peak plasma concentrations occur within 2–3 hr
of oral administration. Meclizine is primarily excreted as metabolites in urine,
with a reported serum half-life of 6 hr. The recommended dose in dogs is 25
mg/day (per dog). When dogs have received meclizine at <33 mg/kg, only mild
hyperactivity or depression has been reported.
Loratadine is a tricyclic, long-acting antihistamine with selective
peripheral histamine H1-receptor antagonist activity. In
people, loratadine is well absorbed orally and extensively metabolized to an
active metabolite. Most of the parent drug is excreted unchanged in the urine.
The mean elimination half-life in people is 8.4 hr. Loratadine appears to have a
large margin of safety in animals. The suggested dose in dogs is 5–10 mg, PO,
once to twice daily (per dog). No deaths were reported at oral dosages up to
5 g/kg in rats and mice. In rats, mice, and monkeys, no clinical signs were seen
at 10 times the maximum recommended human daily oral dose.
Cetirizine, a major metabolite of hydroxyzine, is a piperazine
derivative nonsedating antihistamine. It selectively inhibits peripheral
H1 receptors and does not have significant
anticholinergic or antiserotonergic effects when used at the recommended dosage.
The recommended dosage for histamine-mediated pruritic conditions in dogs is 1
mg/kg, PO, once to twice daily, and 5 mg, PO, bid for cats. The drug appears to
be well tolerated in dogs and cats. The minimum lethal dosage is 237 mg/kg in
mice and 562 mg/kg in rats. Adverse reactions include vomiting, hypersalivation,
sedation, drowsiness, and occasionally hyperactivity.
Treatment of antihistamine toxicosis is primarily
symptomatic and supportive. Emesis should only be considered in asymptomatic
patients. Activated charcoal may be useful for recent ingestion. Symptomatic
patients should be watched for anticholinergic signs (agitation, mydriasis,
tachycardia, decreased intestinal motility) and treated as needed.
Cardiovascular functions (heart rate and blood pressure) and body
temperature should be closely monitored. Propranolol (0.02-0.06 mg/kg, IV)
can be helpful to treat consistent tachycardia in normotensive patients.
Diazepam can be used to control seizures or seizure-type activity.
Physostigmine is recommended to counteract the CNS anticholinergic effects
of antihistamine overdoses in people, although the risk of seizures
associated with this drug may limit its use. IV fluids should be given as
Dextromethorphan is a nonsedating, nonaddictive, centrally
acting opioid cough suppressant. It is available in many OTC cold and cough
medications. At the recommended dosage, it enhances the threshold for coughing.
It is rapidly absorbed orally and converts to the active metabolite dextrorphan
in the liver. Cough suppressant activity can last 3–12 hr, depending on the
formulation. Overdoses can cause CNS and GI effects such as agitation,
hallucination, nervousness, mydriasis, shaking, vomiting, or diarrhea. Some
clinical signs may be similar to those of serotonin syndrome (agitation,
disorientation, hyperthermia, nervousness, shaking). Treatment is mainly
supportive care. Diazepam can be used to control some of the CNS effects.
Phenothiazine tranquilizers (acepromazine or chlorpromazine) or cyproheptadine
(1.1 mg/kg, PO or per rectum, for dogs, and 2–4 mg per cat; repeat once in 6–8
hr if needed) can be given for serotonin syndrome.
Last full review/revision August 2014 by Safdar A. Khan, DVM, MS, PhD, DABVT