Chapter: Modern Pharmacology with Clinical Applications: Drugs Used in Dermatological Disorders

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Photochemotherapy

Photochemotherapy is exposure of the patient to light of an appropriate wavelength after topical application or oral ingestion of a photosensitizing drug.

PHOTOCHEMOTHERAPY

 

 

Photochemotherapy is exposure of the patient to light of an appropriate wavelength after topical application or oral ingestion of a photosensitizing drug. The most com-mon photosensitizing drugs used in dermatology are synthetic psoralens; psoralens also occur naturally in many plants, such as citrus fruits and celery).

 

Psoralen and Ultraviolet A Therapy

 

Psoralens form covalent linkages with pyrimidine bases in DNA when exposed to light of the appropriate wave-length, and if oxygen is present, reactive oxygen species also are generated. Although inhibition of DNA repli-cation may account for some of the beneficial effects of PUVA therapy in certain hyperproliferative disorders such as psoriasis, PUVA has other important biological effects. It suppresses contact hypersensitivity and may evoke other immunological changes by affecting T lym-phocytes and epidermal Langerhans cells. It increases melanin pigmentation in the skin and is useful in treat-ing vitiligo. PUVA also inhibits mast cell release of in-flammatory mediators.

 

Orally administered psoralens are rapidly absorbed (maximum photosensitivity for the most common preparation, 8-methoxypsoralen [Oxsoralen Ultra], is 1–1.5 hours). Although the elimination half-life is 2.2 hours, the skin remains photosensitive for 8 to 12 hours. Most excretion is renal, and the drug does not accumu-late. It can be absorbed if applied topically, and after application to the entire body, therapeutic plasma levels can be detected.

 

PUVA is most useful for the treatment of severe psoriasis. Early (patch and plaque) stage cutaneous T-cell lymphoma (CTCL) also responds to PUVA ther-apy. In addition, patients in advanced stages of CTCL have been treated with a modification of PUVA known as extracorporeal photopheresis. In this therapy, blood from a CTCL patient who has taken psoralen is ex-posed to UVA light and returned to the patient. Lymphocytes are altered or destroyed by the treatment, and theoretically, the return of these abnormal cells triggers an immune response directed against certain lymphocyte surface antigens. The effectiveness of this modality appears to be variable.

 

Both topical and systemic PUVA are useful in some patients with vitiligo, although repigmentation is rarely complete. Other skin diseases for which PUVA may be helpful include atopic dermatitis, dyshidrotic eczema, and polymorphous light eruption.

Nausea is the most common acute side effect. About 36 to 48 hours after therapy, erythema and blistering can occur, especially if the UVA dose is too high or if the patient is exposed to other sources of UVA (such as sunlight). Long-term toxicities include the following:

 

·            Squamous cell carcinoma of the skin (especially of the male genitalia). This risk is increased in patients already at risk because of fair skin, a history of skin cancer, and a history of expo-sure to other cutaneous carcinogens.

 

·            Melanoma. After 15 years or more of PUVA ( 200 treatments) the risk of melanoma in-creases approximately fivefold in patients treated with higher doses in the United States.

 

·            Cataracts. Patients should wear UVA-absorb-ing wraparound sunglasses when exposed to ul-traviolet light during the 24 hours after taking the drug.

 

·              Hyperpigmentation and development of dis-creet dark macules called PUVA lentigines

 

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