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 side 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 that is effective for an animal (see Systemic Pharmacotherapeutics of the Integumentary System: Antihistamine Dosages). Antihistamines may act synergistically with NSAID, glucocorticoids, or fatty acid supplements and may allow dosages of these agents to be reduced in some cases.

Table 3
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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

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 (thus they are contraindicated in cardiac patients), dry mouth, blurred vision (they are 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.

Last full review/revision March 2012 by Michael Shipstone, BVSc, FACVSc, DACVD