Chapt. 9: Drug Allergy Flashcards
During the acute reaction phase of an allergic reaction, what laboratory test are advisable?
Serum tryptase (to prove mast cell involvement)
During the acute reaction phase of an allergic reaction, what laboratory tests are advisable?
ESR
CRP
Liver enzymes to define organ involvement and severity
What are the most common drug classes involved in hypersensitivity (immediate and delayed) reactions?
Antibiotics
NSAIDs
Anticonvulsants
What are some drugs that induce severe systemic forms of delayed-type hypersensitivities?
HLA class 1 allele. Here, HLA testing is recommended before use.
When is a patient’s risk for drug hypersensitivity increased?
During viral infections (EBV, HIV), during or shortly after a severe drug hypersensitivity reaction (‘flare up’) or if high doses, prolonged or repetitive treatment courses are needed (ex. cystic fibrosis)
What is the incidence of ADR?
10-20% of hospitalized patients and up to 25% of outpatients.
Typically, drug allergy affects what organ system?
Skin, but organ involvement (hepatitis) and blood eosinophilia are also common in systemic forms of drug hypersensitivity and may serve as ‘red flags’ for a more severe course.
What are the 2 usual subtype classifications of ADRs?
Type A reactions: predictable from known pharmacologic properties
Type B reactions: unpredictable or unexpected and restricted to a vulnerable subpopulation.
What are the majority of these unexpected type B reactions?
Hypersensitivity reactions. They are responsible for about 1 in 6 of all ADRS.
What comprise the Hypersensitivity reactions?
- Allergic (immune-mediated)
- Pharmacologic (direct interaction with specific immune receptors (HLA, TCR)
- Non-allergic intolerance (also called ‘pseudo-allergic’) reactions without a defined genetic defect
Defines a non-allergic hypersensitivity reaction with a genetic background?
Idiosyncrasy
What is otherwise known as favism?
G6PD deficiency
What is a drug reaction seen with favism?
Hemolytic anemia upon intake of metimazole or one of the other G6PD-dependent drugs
What is the definition of immediate type vs delayed type hypersensitivity?
Onset of symptoms before or after 1 hour
Might help distinguishing whether the probable immunologic mechanism is anti-body mediated (mostly IgE), immediate-type or a T-cell-mediated, delayed-type reaction.
Timing of the reaction
What is more common, immediate type or delayed type reactions?
Delayed-type reactions are much more frequent
Is an atopic genetic background with IgE-mediated response to ingested or inhaled proteins (ex. hay fever) associated with an increased risk for drug hypersensitivity?
No.
What is haptenization?
It is when drugs bind to an endogenous carrier protein. Thus, immunogenic complexes arise and can illicit a complex immune response with B and T cell reactions.
What is the MOA of most drug hypersensitivity reactions?
Due to T-cell stimulations and are caused by direct binding of the drug to a HLA or a T-cell receptor (TCR) molecule.
What does the term p-i concept refer to?
Pharmacological interaction with immune receptors
What are the most common drug classes causing hypersensitivity reaction?
beta-lactam antibiotics and NSAIDs
What are the most common clinical manifestation of drug allergy?
Cutaneous reactions such as maculopapular reactions and urticaria
What are some more severe and potentially life-threatening reactions?
TEN - toxic epidermal necrolysis
SJS - Stevens-Johnson syndrome
DRESS - Drug rash with eosinophilia and systemic symptoms
Immune hepatitis
In the US, how many patients die from ADR?
1 in 300 hospitalized patients, and 6-10% of these reactions are most probably allergic in origin.
