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

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Thalidomide

Thalidomide (Thalomid) is a derivative of glutamic acid that is chemically related to glutethimide.

THALIDOMIDE

 

Thalidomide (Thalomid) is a derivative of glutamic acid that is chemically related to glutethimide. It exerts a number of biological effects as an immunosuppressive, antiinflammatory, and antiangiogenic agent, yet its mechanisms of action have not been fully elucidated. Thalidomide potently inhibits production of tumor necrosis factor (TNF) and interleukin (IL) 12, and its effect on these and other cytokines may account for some of its clinical effects.

 

Its absorption from the gastrointestinal tract is slow, with peak plasma levels being reached after 3 to 6 hours. It appears to undergo nonenzymatic hydrolysis in the plasma to a large number of metabolites. The elimi-nation half-life is approximately 9 hours.

 

Thalidomide is approved for use in the United States for the treatment of cutaneous manifestations of erythema nodosum leprosum, a potentially life-threatening systemic vasculitis that occurs in some pa-tients with leprosy. Although not approved for other in-dications, thalidomide has also been shown to be very effective in the management of Behçet’s disease, HIV-related mucosal ulceration (aphthosis), and select cases of lupus erythematosus.

 

Thalidomide is a highly teratogenic drug, characteris-tically causing phocomelia (aplasia of the midportions of the limbs). Even a single dose may cause fetal malforma-tion. Thalidomide should be prescribed to women of childbearing potential only when no acceptable alterna-tive exists. Because it is not known whether thalidomide is present in the ejaculate of males receiving the drug, male patients must use a latex condom when engaging in sexual activity with women of childbearing potential.

 

Other side effects of thalidomide may include seda-tion (in fact, thalidomide was originally marketed in Europe as a sleeping aid), constipation, and peripheral neuropathy, which may be permanent.

 

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