Drug induced allergy and hypersensitivity

Transcription

1 Drug induced allergy and hypersensitivity Yunita Sari Pane, Aznan Lelo Dept. Pharmacology & Therapeutic School of Medicine Universitas Sumatera Utara 13 Mei 2009, KBK-FK USU, Medan

2 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, ti secondary or indirect effects (eg. bacterial over growth) pseudoallergic drug rx (e.g. opiate reactions, ASA/NSAID reactions) Immunologic (5-10%)

3 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)

4 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 conjunc- tival manifestations only - topical: high incidence of sensitization Scheduling of administration: - intermittent courses: predispose to sensitization

5 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

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

7 Gell and Coombs reactions Type 3: Serum sickness - fever, rash (urticaria, i 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)

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

9 Penicillin Allergy Skin tests: Penicillin G, Prepen (benzyl-penicilloyl- polylysine) false negative rate of up to 7% Resolution of penicillin allergy 50% lose penicillin allergy in 5 yr 80-90% lose penicillin illi allergy in 10 yr

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

11 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 illi courses; 69% to 100% in those with infectious mononucleosis or acute lymphocytic leukemia must be distinguished from hives secondary to ampicillin or amoxicillin

12 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

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

14 ASA & NSAID sensitivity ASA sensitivity: cross-reactivereactive with all NSAIDs that inhibit cyclo-oxygenase 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 ASA-induced urticaria

15 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

16 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- illi allergic individuals).

17 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 d essential.

18 Desensitization to medications Basic approach: administer gradually increasing doses of the drug over a period of hours to days, y, typically beginning with one ten- thousandth of a conventional dose