Drug Hypersensitivity Flashcards
Examples of Type 1 reactions
- allergic rhinitis
- asthma
- systemic anaphylaxis
(mast cell activation)
Examples of Type 2 reactions
Some drug allergies (penicillin)
FcR cells
Examples of Type 3 reactions
Serum sickness
FcR cells, complement
Examples of Type 4a reactions
- Tuberculin reaction
- contact dermatitis
(macrophage activation
Examples of Type 4 b reactions
- chronic asthma
- maculopapular exanthema
(eosinophils)
Examples of Type 4c reactions
- contact dermatitis
- maculopapular and bullous exanthema
- hepatitis
(T cells)
Examples of Type 4 d reactions
- acute generalised exanthematous pustulosis
- Behcet disease
(neutrophils)
Mechanism and examples of Type 1 drugs
(IgE- mediated, immediate reaction)
- beta-lactam antibiotics
- neuromuscular blockers
Mechanism and examples of Type 2 drugs
(IgG/M- mediated cytotoxic)
- heparin
- methyldopa
Mechanism and examples of Type 3 drugs
(IgG/M-mediated immune complexes)
- beta-lactams
- quinidine
- procainamide
Mechanism and examples of Type 4a drugs
(Th1 cells activate monocytes via IGN-G and TNF-a)
- topical antibiotics and antihistamines
- local anaesthetics
Mechanism and examples of Type 4b drugs
(Th2 cells drive eosinophilic inflammation - IL-5,4,13)
- Rifampicin
- pyrazinamide
- INH
Mechanism and examples of Type 4c
(CD41/81 cytotoxic T cells kill targets with perforin)
- Neviropine
- abacavir
- rifampicin
- pyrazinamide
- INH
- carbamazepine
- sulfonamides
Mechanism and examples of Type 4d
(T cells recruit and activate neurophils)
- sulfonamides
- tetracyclines
- cephalosporins
- penicillins
- hydroxychloroquine
- NSAIDs
- azoles
How does a small molecule induce an immune reaction?
Stimulate innate immune system
- bind to proteins and stimulate cells of IIS
Stimulate specific immune system
- couple to carrier protein to form hapten-protein complex
- complex is precessed by APCs
- modified proteins can induce a humoral immune system by stimulating B cells
Drugs that cause majority of adverse reactions
- antibiotics
- general anaesthesia
- ACE-I
- asprin/ NSAIDS
- local anaesthetics
- radio-contrast media
Classification of NSAID hypersensitivity
- asprin-exacerbated respiratory disease
- urticaria exacerbated cutaneous disease
- multiple NSAIDS-induced urticaria/ angioedema
- Single NSIADS IgE allergy
- Single NSAIDS T cell reaction (Non-immediate)
Discuss ACE-I associated angioedema
- vasodilatory effect due to bradykinin
- not immune-related
SCAR reactions
severe cutaneous adverse drug reactions
- mobilliform eruptions
- SJS and TEN
- drug rash with eosinophilia and systemic symptoms
- Lichenoid drug eruptions
- AGEP
Reactions with Rif
- DRESS, LDE, SJS/TEN
- DILI
- AIN
- anaphlyactoid urticaria/ angioedema
Reactions with INH
- DRESS, LDE, SJS/TEN
- DILI
Reactions with pyrazinamide
- SJS/TEN, DRESS
- DILI
Reactions with ethambutol
- DRESS, SJS/TEN
Reactions with fluoroquinolones
Anaphylactoid
Reactions with ethionamide
DRESS, SJS/TEN
Agents responsible for DILI
- antimicrobials
- dietary supplements
- lipid lowering agents
- antineoplastic drugs
- NSAIDS
- psychotropics
- immunosuppressants
Common antimicrobials causing DILI
- amoxil/ calvulanate
- INH
- nitrofurantoin
- Co-trimox
- minocycline
- ciproflox
- azithro
How do genetics play a role in DILI?
- N-acetyltransferase 2 and CYP2E polymorphisms associ with anti-TB DILI
- cytokine polymorphisms associ with diclofenac DILI
- HLA associations with Co-amoxyclav DILI
Main categories of acute renal failure
- tubular necrosis
- interstitial nephritis
- acute glomerulonephritis
Causes of AIN
- antibiotics
- Rif
- herbal/traditional meds
- NSAIDS
- duiretics
- allopurinol
- phenytoin
Histological findings in AIN
- intersitial oedema
- diffuse interstitial infiltrate of inflammatory cells (T-cells and eosinophils)
AIN pathogenesis
Immunologically mediated hypersensitivity reaction to an antigen
Clinical manifestations for drug induced AIN
- rash
- joint pain
- eosinophilia
- eosinophiliuria
Features of Rif-induced AIN
- occurs when reintroduced
- not associated with eosinophilia
- flu-like symptoms, flank pain, hypertension, oliguria, ARF
- can also see acute tubular necrosis
Treatment of drug-related AIN
- cessation of drug (usually resolves in a few days)
- if not:
- renal biopsy
- high dose prednisone
