PHAR3911 - Allergy and Dermatological Reactions

compare Type A and Type B adverse drug reactions

A: predictable, related to pharmacology, reduce dose to manage

B: unpredictable, unrelated to pharmacology, immune medicated, withhold drug to manage

what are the main risk factors for Type B ADR?

female

old

HLA genetic mutations (PGx testing)

drug factors

recurrent exposure

Hx of drug allergy

what are Type 1 allergic drug reactions?

IgE medicated

immediate reaction

caused by protein/ prior exposure

example: anaphylaxis

what are Type 2 allergic drug reactions?

IgG mediated

slower reaction

cause cell or tissue injury

how does penicillin trigger DIIHA (drug-induced immune hemolytic anaemia)?

BPO group acts as little antigen -> binds to RBC -> IgG formation -> lysis of spleen

how does quinidine trigger DIIHA (drug-induced immune hemolytic anaemia)?

acts like hapten -> bind to IgM -> activate on RBC surface -> disrupt osmosis -> IV haemolysis

what are Type 3 allergic drug reactions?

formation of anti-body complexes

delayed reaction

example: serum sickness (reaction to animal antigen where antivenom produced), vasculitis (inflamed blood vessels)

what are Type 4 allergic drug reactions?

T-cell medication

delayed onset

subtypes

example: allergic contract dermatitis, DRESS, TEN SJS

what is an exanthematous rash (Type 4a reaction)?

morbilliform reaction

widespread, itchy, red rash

spontaneous resolution

what is Type 4b reaction?

DRESS

affects multiple organs

fever, rash, exfoliative dermatitis

causes: anticonvulsants, antibiotics

what is Type 4c reaction?

SJS/TEN

blistering disorders

erosion, epidermal detachment, necrosis, fever

SJS: less peeling

TEN: higher peeling

causes: allopurinol, lamotrigine

explain sulfonamide reactions (sulfur allergy)

associated with SJS/TEN

no cross reactivity between arylamine and non-arylamine sulfonamides

explain pseudo allergy & anaphylactoid reaction +example

not mediated by antibodies or T cells

anaphylactoid reactions

drug stimulates release of or activates inflammatory mediators

example: aspirin/ NSAID induced asthma

explain ACE inhibitor angioedema

variable reaction time

swelling of lips, tongue, face

anaphylactoid reaction of inhibited bradykinin

explain red man syndrome

vancomycin reaction

flushing, itching, red rash

caused by degradation of mast cells -> release histamine