Allergy Flashcards
WHO CLASSIFICATION FOR ADVERSE DRUG REACTIONS
i) what is a type A reaction? what is it related to? is it predictable? is it dose dependent? does it have high or low mortality?
ii) give three examples of a type A reaction and what drug causes it
iii) what is a type B reaction? is it predictable? is it dose dep? what is the mortality?
iv) what mechanism is involved in type B reacions? what is it also known as?
i) type A - side effects
- related to drug pharma, predictable, dose dep and low mortality
ii) drowsiness with first gen anti histamines, liver fail in paracetamol OD, nausea and constipation with opiates, dry mouth with tricyclics
iii) type B - allergic reaction
- not directly related to pharmacology, unpredictable, often dose indep, high mortality
iv) type B reac - immunol mechanism - drug hypersensitivity (allergy should only be used when a immunol basis is established)
IMMEDIATE DRUG HYPERSENS REACTIONS - IgE med
i) what is an immediate reaction classed as? give a skin, resp, cardio manifestation? what causes an immediate reaction?
ii) are immediate reactions part of an atopic phenotype?
iii) what can make immediate reactions come on quicker? which drugs may be a bit delayed?
v) after what dose does sensitisation usually occur? how many days does it take to class switch to IgE? what is the key question to ask
i) immed = within one hour of drug admin - caused by mast cell activation
- skin - urticaria/angiodema
- resp - rhinitis, bronchospasm, laryngeal oedema
- CV collapse
ii) may be IgE mediated but not part of atopic pheno (risk similar in atopic and non atopic individuals)
iii) reactions can come on quicker if IV treatment - NSAIDs may be a bit delayed (1hr)
v) usually occurs after first dose (sensitised)
- takes about 14 days to class switch to IgE - develop anaphylaxis after this
- key to ask time between last dose and symptom onset
MAST CELLS
i) where are they found?
ii) which receptors are on their surface? what do they therefore pick up from the circulation?
iii) what happens if an allergen comes along that binds the IgE on mast cell surface?
i) found in tissues
ii) have high affinity IgE receptors on cell surface therefore pick up IgE in the circulation (from B and plas cells)
iii) Cross linking of IgE on mast cell surface > clustering of FCeRI receptors which activates the mast cell
- intracellular portion becomes phosphorylated > activation
- mast cell then degranulates > rel histamine, tryptase > reaction
NON IGE MEDIATED IMMEDIATE DHR
i) name three things that can cause non specific mast cell activation? in which patient group is this more likely to occur in?
ii) what commonly used drug can cause angioedema and inhibit a deactivator of bradykinin?
iii) what may these drugs be given alongside? what type of reaction will this not work for?
i) opiates, myorelaxants, radiocontrast media, vaccines
- more likely to occur in patients with urticaria
ii) ACEi can cause angioedema
iii) can give with anti histamine cover
- wont work if anaphylaxis
TAKING A HISTORY FOR IMMEDIATE DHR
i) what three things can be asked to see if it sounds like an immediate reaction?
ii) name three high risk medications? what dose will it usually occur in?
iii) which drug is unlikely to have an immediate reaction
i) what are the symptoms? how long did it take for the reaction to present? what dose of drug was used?
ii) antibiotics, NSAIDs, taxane chemo
iii) anti hypertensives are unlilkely to give an immed reaction
MAST CELL TRYPTASE
i) when is it released from mast cells? what can it be used to measure?
ii) when should bloods be taken? (3)
iii) what is the sensitivity of measuring mast cell tryptase?
iv) why isnt histamine measured?
i) tryptase is released from mast cells during anaphylaxis
- serum levels can be used to confirm acute anaphylaxis
ii) take bloods 1-2 hours after symptom onsey then again after 24hrs
iii) sensitivity around 70% - see increased followed by normalisation
iv) dont measure histamine as its unstable and degrades quickly
NON IMMEDIATE DHR - KEY FEATURES
i) is it more or less common than immediate? is it directly related to drug dose?
ii) how long does it usually take if patient has been treated with drug before? how long if it is first sensitisation?
iii) what are the clinical features not in keeping with?
iv) what is the biggest group of meds that cause this reaction?
v) what is the most dangerous non immed DHR to look out for?
i) more common than immed
- not directly related to drug dose
ii) usually happens 3-5 days if treated with drug before and 5-8 days if first sensitisation
iii) clin features not inkeeping with mast cell degranulation
iv) antimicrobials are they biggest group
v) look out for steven johnson syndrome/toxic epiderminal necrolysis
STEVEN JOHNSON SYNDROME/TENS
i) name three symptoms?
ii) does it affect more men or women? how old?
iii) how many days after first dose does it usually occur? what are the two most common culprit drugs?
iv) what is the mortality? what increases this?
v) name three features that may be seen
i) fever, cough, conjunctivitis, mucocytis
ii) affects mostly men under 30yrs
iii) usually occurs 3-8 days after the first dose
- antibiotics and anti convulsants are most common culprit
iv) mortality is very high and gets worse with each exposure
v) may see erythema multiforme (target lesions), epidermal necrolysis (needs inpatient mx), mucocytis
TYPE IV HYPERSENSITIVITY
i) when does it usually present? what is it mediated by?
ii) what type of rash is seen? how may the skin appear?
iii) how long does it take to fade? is there systemic upset?
i) usually presents 3-8 days into course (T cell mediated)
ii) see maculopapular rash
- skin may be dry or inflammed
iii) takes days/weeks to fade - doesnt stop when drug is stopped
- no systemic upset
B LACTAM ALLERGY
i) what is the reported prevalence? what is the true prevalence?
ii) give two reasons why it may be over reported
iii) why is it hard to test for this kind of allergy?
iv) what is the first line test? what is done if test is positive
i) reported - 10% but actual - 1-2%
ii) over reported due to - sensitisation is lost at a rate of 10% per year
- rash caused by something else
iii) hard to test because antigens causing the drug allergy are metabolites of the drug rather than the drug itself
iv) first line do skin prick testing with beta lactams and reagents
- negative results habe high neg predictive value
- if positive > do challenge testing with an alternative to demonstrate tolerance
CHALLENGE TESTING
i) where must it be done for high risk patients?
ii) how often is dose increased until therapeutic dose is reached
iii) name two cons
iv) name a pro
v) when may a referral to immunology be useful? (2)
i) must be done in hospital
- want to use oral where possible (reactions slower and milder)
ii) inc dose every 30 min until therapeutic dose reached
iii) time consuming, risk of allergic reac, doesnt pick type IV hypersens up well
iv) pro - large majority of patients can be ‘delabelled’
v) if the drug will be needed again, if choice restricted, if cross reactivity questions, if dx doubt
WHAT CAN BE DONE FOR DHR
i) what is the mainstay?
ii) in which syndrome is the offending drug absolutely contraindicated?
iii) what can be offered if there is a type IV reaction? what if there is type I?
i) mainstay is avoidance
ii) SJS - absolute contraindication
iii) if type IV - related drugs may be offered
type I - avoid entire class
