Antimalarial Drugs

Like dapsone, the antimalarial drugs chloroquine, hy-droxychloroquine, and quinacrine are useful in some noninfectious skin diseases, although the mechanism of their therapeutic effect is unknown. Their pharmacology is discussed in Chapter 53.

Antimalarial drugs have many effects, including impairment of lysosomal phagosomal activity, inhibition of neutrophilic iodination and locomotion, and diminution of macrophage and T-cell responsiveness in vitro. Chloroquine (Aralen) and hydroxychloroquine (Plaquenil) also form complexes with hepatic por-phyrins and can chelate iron, thereby enhancing their urinary excretion. Both drugs have an affinity for melanin, which may at least partially explain their oph-thalmological toxicities (retinopathy).

Hydroxychloroquine is approved for the treatment of both systemic and cutaneous lupus erythematosus. Both chloroquine and quinacrine (Atabrine) are also effective in this skin disease. Low-dose chloroquine is used for the therapy of porphyria cutanea tarda in patients in whom phlebotomy has failed or is contraindi-cated. Other skin diseases in which the drugs are useful (after sunscreens and avoidance of sun exposure) include polymorphous light eruption and solar urticaria.

The duration of treatment for skin diseases is often longer than it is for malaria, and therefore, dose-related toxicities are important. The most serious toxicities are ophthalmological. Reversible alterations include ciliary body dysfunction and corneal changes with edema and deposits. Irreversible retinopathy also occurs; however, it is less common with quinacrine than with the other two drugs. Toxicity may be asymptomatic, but the earliest symptoms are night blindness, scotoma, or tunnel vision.

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