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Chapter: Basic & Clinical Pharmacology : Immunopharmacology

Immunologic Reactions to Drugs & Drug Allergy

Drugs also activate the immune system in undesirable ways that are manifested as adverse drug reactions.

IMMUNOLOGIC REACTIONS TO DRUGS & DRUG ALLERGY

 

The basic immune mechanism and the ways in which it can be sup-pressed or stimulated by drugs have been discussed in previous sections. Drugs also activate the immune system in undesirable ways that are manifested as adverse drug reactions. These reactions are generally grouped in a broad classification as “drug allergy.” Indeed, many drug reactions such as those to penicil-lin, iodides, phenytoin, and sulfonamides are allergic in nature. These drug reactions are manifested as skin eruptions, edema, ana-phylactoid reactions, glomerulonephritis, fever, and eosinophilia.

Drug reactions mediated by immune responses can have sev-eral different mechanisms. Thus, any of the four major types of hypersensitivity discussed earlier can be associated with allergic drug reactions:

·  Type I: IgE-mediated acute allergic reactions to stings, pollens,and drugs, including anaphylaxis, urticaria, and angioedema. IgE is fixed to tissue mast cells and blood basophils, and after interaction with antigen the cells release potent mediators.

 

·  Type II: Drugs often modify host proteins, thereby elicitingantibody responses to the modified protein. These allergic responses involve IgG or IgM in which the antibody becomes fixed to a host cell, which is then subject to complement-depen-dent lysis or to antibody-dependent cellular cytotoxicity.

 

·  Type III: Drugs may cause serum sickness, which involvesimmune complexes containing IgG complexed with a foreign antigen and is a multisystem complement-dependent vasculitis that may also result in urticaria.

 

·  Type IV: Cell-mediated allergy is the mechanism involved in al-lergic contact dermatitis from topically applied drugs or indura-tion of the skin at the site of an antigen injected intradermally.

 

In some drug reactions, several of these hypersensitivity responses may occur simultaneously. Some adverse reactions to drugs may be mistakenly classified as allergic or immune when they are actually genetic deficiency states or are idiosyncratic and not mediated by immune mechanisms (eg, hemolysis due to pri-maquine in glucose-6-phosphate dehydrogenase deficiency, or aplastic anemia caused by chloramphenicol).


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