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Cold and Cough Medications (Toxicity)



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 amounts.

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 intestinal secretions/motility).

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 needed.


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

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