White : Diseases of the Skin - Systemic Therapies

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Gary M. White & Neil H. Cox

Diseases of the Skin

4	Systemic Therapies

ANTIHISTAMINES

Oral antihistamines are widely used in dermatology. It is helpful to divide drugs with antihistamine effects into the following groups, the first two of which are marketed as antihistamines for dermatologic conditions.

•	Conventional or first-generation ‘sedating' antihistamines, for example chlorpheniramine (chlorphenamine), cyproheptadine, hydroxyzine, alimemazine (trimeprazine), and promethazine. (Note: patients taking these drugs should be warned about drowsiness and the potential impact on driving or operating machinery).
•	Second-generation ‘non-sedating' antihistamines, for example acrivastine, loratadine or desloratidine, cetirizine or levocetirizine, fexofenadine, and mizolastine.
•	Other drugs that have antihistaminic or antipruritic activity, for example amitriptyline and doxepin.
•	H 2 antagonists (e.g. cimetidine)—may be an adjunct in treatment of urticaria; some studies show benefit in clearing viral warts.

The importance of this division is that the second-generation agents are much more specifically antihistaminic; this is beneficial in avoidance of sedation, but it does mean that their value is limited in itch that is not primarily related to histamine (although some do have other effects, for example on eosinophils or on cytokine activity). Thus, for example, patients with eczema often derive little benefit from non-sedating antihistamines. Even in urticaria, where histamine is important, the sedative effect of an older agent at nighttime can be beneficial.

Some side effects of antihistamines are important. Most are metabolized in the liver; those that are metabolized by cytochrome P450 (especially mizolastine and terfenadine) should be avoided in conjunction with grapefruit juice or with drugs that block this enzyme (e.g. azoles and macrolides). There is a risk in such situations, or in the elderly or patients with liver or cardiac disease, of cardiac arrhythmias. Additionally, some (mainly sedating) antihistamines have anticholinergic activity and should be avoided in patients with glaucoma, hypertension, airway obstruction, or prostatism.

PRACTICE POINTS

•	It can be very useful in difficult urticaria to use a non-sedating antihistamine in the daytime and a sedating agent at night.
•	Non-sedating antihistamines are generally of little value in the treatment of eczema; an appropriate-potency topical corticosteroid is dramatically more helpful.
•	Beware of exceeding recommended doses of non-sedating antihistamines, especially if there is a potential for drug interactions.
•	Grapefruit juice interferes with the metabolism of some non-sedating antihistamines.