Drug Allergies And Desensitisation Flashcards
ADR
Type A: tocixity, side effects, interactions
Type B (unpredicted): immunologic / genetic susceptibility (G5PD, COX1)
DA history
- Onset - when did the reaction occur?
- Character - what was the reaction?
2A. How severe? - anaphylaxis, mucous membrane erosion, blisters - Timing - in relation with medication administration
- Other drugs or co-factors
- Further exposure to index / related medication
- Is the medication essential?
Timing of DA
A. Immediate onset
- 1-6 hours
- Urticaria, angioedema, flushing, anaphylaxis
- Usually type 1 mediated hypersensitivity - immediate read tests
B. Delayed
- > 6 rashes
- MP rashes, DRESS, AGEP, SDRIFE, SJS/TEN
- Usually type 4 related hypersensitivity - patch
Beta lactams
8-15% population labelled penicillin allergy
- However 90% found to tolerate penicillin well
Skin testing sensitivity poor
Not useful for organ limited disease
3 different components:
- Beta lactam
- Side chain
- Others
Beta lactam degradation and fragmentation
- Conjugates to other proteins which causes allergenic
Evaluation of hypersensitivity reaction
Type 1 - immediate
Immediate reading tests - 10-15 minutes
- Skin prick test
- Intradermal test
Type 4 - delayed
- Read after 3-4 days
- Patch test
Drug provocation test
To enable de-labeling of allergy
To provide alternatives in proven hypersensitivity to particular drug
Must exclude those with severe allergic reactions
Penicillin desensitisation
Pre-emptive desensitisation is not useful
Only desensitise when there is lack of alternative antibiotic
Contraindications: severe life threatening reactions
What happens during drug desensitisation
- Formation of small clusters of Ag-IgE-FceRI complexes and membrane rearrangement
- Uncopling of downstream activating signals
- Impaired internalisation and calcium chanel desensitisation
- Desensitised mast cells exhibits resistance to activation when re-challenged with same antigen
NSAIDs
0.5 - 1.9% of population
As higher as 25-35% for those with asthma, nasal polyps, chronic urticaria
COX-1 intolerance
- Blocking of cyclo-oxygenase pathway leading to shifting to lipo-oxygenase pathway
Single NSAID reactor vs multiople NSAIDs reactor
- Check whether patient tolerated any other NSAIDs
Aspirin desensitisation
NOT permanent
Loss of desensitised state if medicatiosn skipped > 2-3 days
Will need repeat protocol
Low dose desensitisation
- Not suitable for loading dose
High dose desensitisation - for NSAID exacerbated respiratory disease
Strongest prediction of failure: angioedema
Mechanism:
Decreased expression of CysLT1 receptor
Inhibilition of IL4 production
May have genetic predisposition
