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Chapter: Clinical Pharmacology: Antineoplastic drugs

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Interferons

A family of naturally occurring glycoproteins, interferons are so named because of their ability to interfere with viral replication.

Interferons

A family of naturally occurring glycoproteins, interferons are so named because of their ability to interfere with viral replication. These drugs exhibit anticancer activity as well as activity against condylomata acuminata (soft, wartlike growths on the skin and mucous membrane of the genitalia caused by a virus). The three types of interferons are:

 

·                 alfa interferons derived from leukocytes

 

·                 beta interferons derived from fibroblasts (connective tissuecells)

 

·                 gamma interferons derived from fibroblasts and lympho-cytes.

Pharmacokinetics

 

After I.M. or subcutaneous administration, interferons are usually well absorbed. Information about their distribution is unavailable.

Metabolism and excretion

 

Alfa interferons are filtered by the kidneys, where they’re degrad-ed. Liver metabolism and biliary excretion of interferons are negli-gible.

Pharmacodynamics

 

Although their exact mechanism of action is unknown, interferons appear to bind to specific membrane receptors on the cell surface. When bound, they initiate a sequence of intracellular events that includes the induction of certain enzymes.

Running interference

 

This process may account for the ability of interferons to:

 

·                 inhibit viral replication

 

·                 suppress cell proliferation

 

·                 enhance macrophage activity (engulfing and destroying mi-croorganisms and other debris)


·                 increase cytotoxicity of lymphocytes for target cells.

Pharmacotherapeutics

 

Alfa interferons have shown their most promising activity in treat-ing blood malignancies, especially hairy cell leukemia. Their ap-proved indications currently include:

·                 hairy cell leukemia

·                 AIDS-related Kaposi’s sarcoma

·                 condylomata acuminata.

 

Interfering in these areas as well…

Alfa interferons also demonstrate some activity against chronic myelogenous leukemia, malignant lymphoma, multiple myeloma, melanoma, and renal cell carcinoma.

Drug interactions

 

Interferons interact with other drugs:

 

§    They may enhance the CNS effects of CNS depressants and sub-stantially increase the half-life of methylxanthines (including theo-phylline and aminophylline).

 

§    Concurrent use with a live virus vaccine may potentiate replica-tion of the virus, increasing the adverse effects of the vaccine and decreasing the patient’s antibody response.

 

§    Bone marrow suppression may be increased when an interferon is used with radiation therapy or a drug that causes blood abnor-malities or bone marrow suppression.

 

§    Alfa interferons increase the risk of kidney failure from interleukin-2. (See Adverse reactions to interferons.)

 

 

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