Drug allergy reactions
➢ DEFINITION AND CLASSIFICATION
Adverse drug reactions (ADRs) are broadly divided into predictable (related to pharmacologic
actions of the drug in otherwise normal individuals) and unpredictable reactions (related to an
individual’s immunological response and, on occasion, genetic differences in susceptible
patients). Drug allergy is a type of unpredictable reaction.
The term "drug hypersensitivity "refers to objectively reproducible symptoms or signs initiated
by exposure to a drug at a dose normally tolerated by non-hypersensitive persons. "Drug allergy"
refers to immunologically mediated drug hypersensitivity reactions. These may be either
immunoglobulin E (IgE)–mediated (immediate) or non–IgE-mediated (delayed) hypersensitivity
reactions.
MECHANISMS
A drug allergy may be IgE or non-IgE mediated.
• In IgE-mediated reactions, (e.g., urticaria, angioedema, anaphylaxis). Drug allergens bind
to IgE antibodies, which are attached to mast cells and basophils, resulting in IgE cross-
linking, cell activation, and release of preformed and newly formed mediators.
• In non–IgE-mediated drug allergy, the mechanisms include:
➢ Cytotoxic reactions involving the interaction of IgG or IgM antibodies and complement
with a drug allergen associated with cell membranes (e.g., immune hemolytic anemia,
thrombocytopenia),
➢ drug immune complex reactions (e.g., serum sickness and drug-induced lupus), and
➢ T-cell–mediated reactions.
RISK FACTORS FOR DRUG ALLERGY
Drug Factors
• Nature of the drug
• Degree of exposure (dose, duration, frequency)
• Route of administration
• Cross-sensitization
Host Factors
• Age and Sex
, • Genetic factors (HLA type, Acetylator status)
• Concurrent medical illness (e.g., Epstein-Barr Virus (EBV), human immunodeficiency virus
(HIV), asthma)
• Previous drug reaction
• Multiple allergy syndrome
➢ Drug Factors
I) Nature of the drug
It is difficult to predict the sensitizing capacity of a drug prior to widespread clinical use on the
basis of its chemical structure. When a chemical substance is clearly protein-reactive, a high
incidence of sensitization may be expected. Many highly allergenic drugs are not clearly
chemically reactive. In this situation, it is probable that metabolic products of the drugs or minor
contaminants are much more reactive, and are responsible for clinical sensitization. Penicillin,
aspirin, and sulfonamides account for over 80 percent of allergic drug reactions.
II) Degree of exposure (dose, duration, frequency)
There is some evidence that sensitization is more likely with higher drug doses and prolonged
administration, but clinically this does not appear to be important. Of greater importance are
intermittent courses of moderate drug doses that clearly predispose to sensitization; prolonged
treatment without free intervals is less likely to do so.
III) Route of Administration
Topical application of a drug is associated with a high incidence of sensitization and should be
avoided with certain agents, especially on inflamed skin. Penicillin and sulfonamides are no
longer used topically because of this risk.
Oral administration of a drug is generally safer than any type of parenteral administration;
however, severe reactions have followed this mode of administration. The increased use of
penicillin orally may be a reason why the risk of penicillin sensitization has been decreasing.
The intravenous route may be the least sensitizing form of parenteral administration although it
has been associated with catastrophic anaphylactic reactions
IV) Cross-Sensitization
Once sensitization to a drug has occurred, the possibility exists of reactivity either to drugs with
a close structural chemical relationship or to immunochemically similar metabolites. The range
of cross-sensitization varies greatly among individuals and is often impossible to predict e.g. the
cross-reactivity seen among penicillins and cephalopsporins.
➢ Host Factors
I) Age and sex
➢ DEFINITION AND CLASSIFICATION
Adverse drug reactions (ADRs) are broadly divided into predictable (related to pharmacologic
actions of the drug in otherwise normal individuals) and unpredictable reactions (related to an
individual’s immunological response and, on occasion, genetic differences in susceptible
patients). Drug allergy is a type of unpredictable reaction.
The term "drug hypersensitivity "refers to objectively reproducible symptoms or signs initiated
by exposure to a drug at a dose normally tolerated by non-hypersensitive persons. "Drug allergy"
refers to immunologically mediated drug hypersensitivity reactions. These may be either
immunoglobulin E (IgE)–mediated (immediate) or non–IgE-mediated (delayed) hypersensitivity
reactions.
MECHANISMS
A drug allergy may be IgE or non-IgE mediated.
• In IgE-mediated reactions, (e.g., urticaria, angioedema, anaphylaxis). Drug allergens bind
to IgE antibodies, which are attached to mast cells and basophils, resulting in IgE cross-
linking, cell activation, and release of preformed and newly formed mediators.
• In non–IgE-mediated drug allergy, the mechanisms include:
➢ Cytotoxic reactions involving the interaction of IgG or IgM antibodies and complement
with a drug allergen associated with cell membranes (e.g., immune hemolytic anemia,
thrombocytopenia),
➢ drug immune complex reactions (e.g., serum sickness and drug-induced lupus), and
➢ T-cell–mediated reactions.
RISK FACTORS FOR DRUG ALLERGY
Drug Factors
• Nature of the drug
• Degree of exposure (dose, duration, frequency)
• Route of administration
• Cross-sensitization
Host Factors
• Age and Sex
, • Genetic factors (HLA type, Acetylator status)
• Concurrent medical illness (e.g., Epstein-Barr Virus (EBV), human immunodeficiency virus
(HIV), asthma)
• Previous drug reaction
• Multiple allergy syndrome
➢ Drug Factors
I) Nature of the drug
It is difficult to predict the sensitizing capacity of a drug prior to widespread clinical use on the
basis of its chemical structure. When a chemical substance is clearly protein-reactive, a high
incidence of sensitization may be expected. Many highly allergenic drugs are not clearly
chemically reactive. In this situation, it is probable that metabolic products of the drugs or minor
contaminants are much more reactive, and are responsible for clinical sensitization. Penicillin,
aspirin, and sulfonamides account for over 80 percent of allergic drug reactions.
II) Degree of exposure (dose, duration, frequency)
There is some evidence that sensitization is more likely with higher drug doses and prolonged
administration, but clinically this does not appear to be important. Of greater importance are
intermittent courses of moderate drug doses that clearly predispose to sensitization; prolonged
treatment without free intervals is less likely to do so.
III) Route of Administration
Topical application of a drug is associated with a high incidence of sensitization and should be
avoided with certain agents, especially on inflamed skin. Penicillin and sulfonamides are no
longer used topically because of this risk.
Oral administration of a drug is generally safer than any type of parenteral administration;
however, severe reactions have followed this mode of administration. The increased use of
penicillin orally may be a reason why the risk of penicillin sensitization has been decreasing.
The intravenous route may be the least sensitizing form of parenteral administration although it
has been associated with catastrophic anaphylactic reactions
IV) Cross-Sensitization
Once sensitization to a drug has occurred, the possibility exists of reactivity either to drugs with
a close structural chemical relationship or to immunochemically similar metabolites. The range
of cross-sensitization varies greatly among individuals and is often impossible to predict e.g. the
cross-reactivity seen among penicillins and cephalopsporins.
➢ Host Factors
I) Age and sex
