DRUG ALLERGY

DRUG ALLERGY
Adverse drug reactions - majority of iatrogenic illnesses - 1% to 15% of drug courses Non-immunologic (90-95%): side effects, toxic reactions, drug interactions, secondary or indirect effects (eg. bacterial overgrowth) pseudoallergic drug rx (e.g. opiate reactions, ASA/NSAID reactions) Immunologic (5-10%)

Drugs as immunogens
Complete antigens - insulin, ACTH, PTH - enzymes: chymopapain, streptokinase - foreign antisera e.g. tetanus antitoxin Incomplete antigens - drugs with MW < 1000 - drugs acting as haptens bind to macromolecules (e.g. proteins, polysaccharides, cell membranes)

Factors that influence the development of drug allergy

Route of administration: - parenteral route more likely than oral route to cause sensitization and anaphylaxis - inhalational route: respiratory or conjunctival manifestations only - topical: high incidence of sensitization Scheduling of administration: - intermittent courses: predispose to sensitization

Factors that influence the development of drug allergy

Nature of the drug: 80% of allergic drug reactions due to: - penicillin - cephalosporins - sulphonamides (sulpha drugs) - ASA/NSAIDs

Gell and Coombs reactions

Type 1: Immediate Hypersensitivity - IgE-mediated - occurs within minutes to 4-6 hours of drug exposure Type 2: Cytotoxic reactions - antibody-drug interaction on the cell surface results in destruction of the cell eg. hemolytic anemia due to penicillin, quinidine, quinine,cephalosporins

Gell and Coombs reactions

Type 3: Serum sickness - fever, rash (urticaria, angioedema, palpable purpura), lymphadenopathy, splenomegaly, arthralgias - onset: 2 days up to 4 weeks - penicillin commonest cause Type 4: Delayed type hypersensitivity - sensitized to drug, the vehicle, or preservative (e.g. PABA, parabens, thimerosal)

Penicillin Allergy
beta lactam antibiotic Type 1 reactions: 2% of penicillin courses Penicillin metabolites: - 95%: benzylpenicilloyl moiety (the major determinant) - 5%: benzyl penicillin G, penilloates, penicilloates (the minor determinants)

Penicillin Allergy

Skin tests: Penicillin G, Prepen (benzylpenicilloyl-polylysine): false negative rate of up to 7%

Resolution of penicillin allergy - 50% lose penicillin allergy in 5 yr - 80-90% lose penicillin allergy in 10 yr

Cephalosporin allergy
beta-lactam ring and amide side chain similar to penicillin degree of cross-reactivity in those with penicillin allergy: 5% to 16% skin testing with penicillin determinants detects most but not all patients with cephalsporin allergy

Ampicillin rash

non-immunologic rash maculopapular, non-pruritic rash onsets 3 to 8 days into the antibiotic course incidence: 5% to 9% of ampicillin or amoxicillin courses; 69% to 100% in those with infectious mononucleosis or acute lymphocytic leukemia must be distinguished from hives secondary to ampicillin or amoxicillin

Sulphonamide hypersensitivity

sulpha drugs more antigenic than beta lactam antibiotics common reactions: drug eruptions (e.g. maculopapular or morbilliform rashes, erythema multiforme, etc.) Type 1 reactions: urticaria, anaphylaxis, etc. no reliable skin tests for sulpha drugs re-exposure: may cause exfoliative dermatitis, Stevens-Johnson syndrome

ASA and NSAID sensitivity

Pseudoallergic reactions - urticaria/angioedema - asthma - anaphylactoid reaction prevalence: 0.2% general population 8-19% asthmatics 30-40% polyps & sinusitis ASA quatrad: Asthma, Sinuitis, ASA sensitivity, nasal Polyps (ASAP syndrome)

ASA & NSAID sensitivity

ASA sensitivity: cross-reactive with all NSAIDs that inhibit cyclo-oxygenase

ASA & NSAID sensitivity

no skin test or in vitro test to detect ASA or NSAID sensitivity to prove or disprove ASA sensitivity: oral challenge to ASA (in hospital setting) ASA desensitization: highly successful with ASA-induced asthma; less successful with ASAinduced urticaria

Allergy skin testing

Skin tests to detect IgE-mediated drug reactions is limited to: Complete antigens - insulin, ACTH, PTH - chymopapain, streptokinase - foreign antisera Incomplete antigens (drugs acting as haptens) - penicillins - local anesthetics - general anesthetics

Management of drug allergy

Identify most likely drugs (based on history). Perform allergy skin tests (if available). Avoidance of identified drug or suspected drug(s) is essential. Avoid potential cross-reacting drugs (e.g. avoid cephalosporins in penicillin-allergic individuals).

Management of drug allergy

A Medic-Alert bracelet is recommended. Use alternative medications, if at all possible. Desensitize to implicated drug, if this drug is deemed essential.

Desensitization to medications

Basic approach: administer gradually increasing doses of the drug over a period of hours to days, typically beginning with one tenthousandth of a conventional dose

TERIMA KASIH