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Antihistamines for Integumentary Disease

By Michael Shipstone, BVSc, FACVSc, DACVD, Queensland Veterinary Specialists

Antihistamines block either H1 or H2 receptors. H1 receptors are responsible for pruritus, increased vascular permeability, release of inflammatory mediators, and attraction of inflammatory cells. H1 blockers act by competing with histamine for H1-receptor sites on effector cells (they do not block release of histamine but can antagonize its effects). They also have anticholinergic, sedative, and local anesthetic effects and vary greatly in their potency, dosage, incidence of adverse effects, and cost.

Second-generation H1 blockers (eg, terfenadine, cetirazine, loratadine, astemazole) are less likely to cross the blood-brain barrier, or they have a low affinity for brain compared with peripheral H1 receptors. They have not proved useful to date in controlling pruritus in small animals. Responses to antihistamines vary considerably, and several trials may be necessary to find one effective for an animal (see Table: Antihistamine Dosages). Antihistamines may act synergistically with NSAIDs, glucocorticoids, or fatty acid supplements and may allow dosages of these agents to be reduced in some cases.

Antihistamine Dosages

Drug

Dosage

Diphenhydramine

2–4 mg/kg, bid-tid

Hydroxyzine

0.5–2 mg/kg, tid-qid

Clorpheniramine

Cats: 2–4 mg, bid

Dogs <20 kg: 4 mg, tid

Dogs >20 kg: 8 mg, tid; 0.25–0.5 mg/kg, tid

Cyproheptadine

0.25–0.5 mg/kg, tid; 1.1 mg/kg, bid

Terfenadine

5 mg/kg, bid

Clemastine

Cats: 0.05 mg/kg, bid

Dogs: 0.1 mg/kg, bid

Trimeprazine

1 mg/kg, bid

Cetirizine

Dogs: 1 mg/kg or 10–20 mg per dog, once or twice daily

Cats: 1 mg/kg or 5 mg per cat, once or twice daily

Fexofenadine

Dogs: 2–5 mg/kg, once or twice daily

Cats: 10–15 mg per cat, once or twice daily

First-generation antihistamines may cause drowsiness or GI signs (eg, vomiting, diarrhea). Overdoses may cause CNS hyperexcitability and may be fatal. Anticholinergic properties lead to hypertension (and thus contraindicated in cardiac patients), dry mouth, blurred vision (contraindicated in glaucoma), and urinary retention. Hydroxyzine is teratogenic. They may also stimulate appetite (particularly cyproheptadine).

Second-generation antihistamines are cardiotoxic at high doses. High doses of terfenadine and astemizole lead to prolonged QT intervals and arrhythmias (eg, ventricular tachycardia, cardiac arrest). Cardiotoxicity has been reported only as a result of overdose in animals with impaired hepatic metabolism.

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