Resumo de Hypersensitivity (drug Allergy)

HYPERSENSITIVITY (DRUG ALLERGY)

This is the largest single group of untoward drug effects. Allergic reactions are usually not dose related and independent of the pharmacologic properties of the drug molecule. They are associated with an altered reactivity or sensitization of the patient resulting from the prior exposure to a drug or chemical that behaves like an allergen. Macromolecules (proteins, peptides) can act as complete antigens , but most drugs are small molecules and do not stimulate antibody production. They combine with other carrier molecules and function as haptens or partial antigen, activating the reticulo-endithelial system, resulting in the production of antibodies to the drug molecule. A subsequent exposure to the same drug elicits an antigen-antibody reaction that produces symptoms like itching, oedema, congestion, and wheezing. Allergic drug reactions are either immediate (anaphylaxis, urticaria) or delayed (serum sickness).
Immediate hypersensitivity develops within minutes of drug exposure. This involves formation of specific antibodies called reagins that belong to IgE class. Upon re-exposure, the antigen combines with the antibodies on the target tissue, and certain natural substances like histamine, 5-hydroxytrytamine, slow reacting substances (SRS-A), bradykinin, and prostaglandins are liberated. These substances react with smooth muscles of many tissues to produce characteristic signs of the allergic reaction like bronchoconstriction and vasodilation. The symptoms may be very mild (rash, itching, urticaria) or serious (respiratory distress, severe hypertension ? termed anaphylactic shock) which requires immediate attention to prevent death. Immediate immune reactions like anaphylactic shock, asthma rhinitis and angioneurotic oedema occur within a few minutes of re-exposure, e.g., penicillin allergy. Grave concern about such reaction is that they are totally unpredictable, and quick recognition with proper treatment are essential to avoid serious consequences.
Delayed hypersensitivity reactions develop slowly following drug challenge. The allergen reacts with preformed antibodies that are bound to sensitized lymphocytes. The clinical picture of delayed hypersensitivity indices a diffuse rash, fever, angioedema, swollen lymph nodes, and stiff joints. This syndrome is referred to as serum sickness. This name is derived from the fact that the allergic response results from damage produced by the circul;ating immune complexes that may lodge in small vessels. Sometimes the liver, kidney, and bone marrow may also be damaged.

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