Drug Allergy Flashcards
(36 cards)
How many people does drug hypersensitivity affect?
- 50000 UK hospital admissions/ year
- 10% of population report penicillin allergy
- In anaesthetics 1/10000-20000
- Majority, had a known reaction to drug already
What is a type A adverse drug reaction?
- related to the pharamcology of drug
- predictable
- usually dose dependent
- high morbidity, low mortality
Give an example of a type A adverse drug reaction
Drowsiness with 1st gen anti histamines
Liver failure with paracetamol overdose
Nausea + constipation with opiates
Dry mouth with TCAs
What is a type B adverse drug reaction?
- not directly related to pharmacology
- unpredictable
- (often) dose independent
- high mortality
Give an example of a type B adverse drug reaction
- anything that resembles “allergy”
Describe an IMMEDIATE DHR
Timing, symptoms
Mechanism
- occurs within 1 hour of first dose
Clinical features of mast cell degranulation!
- Skin: urticaria, angioedema
- Respiratory: rhinitis, bronchospasm, laryngeal oedema
- Gut: diarrhoea
- CV collapse
- May be IgE mediated, or a form of non-allergic immediate DHR
- Recedes rapidly after drug cessation
State 3 drugs that can cause non-IgE mediated immediate DHR
- Non- specific mast cell activators: opiates, myorelaxants, radiocontrast media
- ACEi
- NSAIDs
What is a common side effect of non-specific mast cells activators?
- Itching
- A patient who recieves opiates, myorelaxants and radiocontrast media can appear to. be in anaphylactic shock due to summation
Describe the events the follow mast cell IgE ligation
- IgE binds to its specific allergen
- Cross linking of IgE antibodies by allergen leads to clustering of FcεR1 receptors
- The intracellular portion of the receptor becomes phosphorylated
- Resulting in intracellular cascade which leads to cellular activation
- Mast cell “degranulates” releasing histamine, tryptase and other pre-formed mediators
In which situations may the onset of symptoms vary in immediate DHR
- IV treatments often have a quicker onset
- NSAIDs may be a little delayed, still within an hour
What questions should you make sure you ask in Hx?
- Which drug?
- When?
- Nature of symptoms
- At what stage in the course did it happen?
- What was the time between LAST dose and symptoms onset?
- How long did it last once drug was stopped?
- Has it been subsequently tolerated?
How long does it take for IgE response
- IgE drug allergies take a few weeks as you need to make the antibodies
- About 14 days
- May vary if already sensitised
Generally speaking what kind of drugs cause IgE allergy
- Naturally occuring protein derived drugs stimulate IgE
- Biggest category: antimicrobials, myorelaxants, taxene based chemo
How does atopy affect drug allergy?
- DHR is not part of the “atopic” phenotype of asthma, eczema, rhinitis and food allergy
- The risk is similar in atopic and non-atopic patients
What questions should you ask if you’re considering an immediate DHR as a differential?
- What was the drug? What was the timing? What were the symptoms? How did they resolves?
- Does the Hx sound like an immediate reaction?
- Does it change what medication you would use going forward?
- Do i need advice?
How might a patient who has improved from a DHR following iV treatment appear?
- Hypotensive
- Resp compromise
- May not have skin signs
What is adrenaline treatment effective?
- if it could be a drug allergy, do not delay adrenaline
- Adrenaline should be given promptly
- If patient arrests
How would you know if your patient has arrested?
Pulseless electrical activity (PEA) is characteristic
How is mast cell tryptase used in the diagnosis of anaphylaxis?
When might this be helpful?
- Serum tryptase easier to meaure in lab than histamine
- Take blood 1-2 hours after symptoms onset and after 24 hours
- Increase followed by normalisation confirms
- 70% sensitive
- To confirm anaphylaxis in sedated patient
How does an allergist approach immediate DHR
- The HISTORY is everything
- Diagnostic test rare, other than drug challenges which are expensive and dangerous
- Pragmatic approach vs definitive (should challenge patients at high risk or low risk for confirmation)
B Lactam allergies are reported by 10% of population however the true prevalence is closer to 1-2%. Why is it so over-reported?
- Patients may have reaction in childhood but sensitisation is lost at a rate of 10%/yr, label persists
- “Rash” result of infection not drug
- Different drugs caused the rash
Give 3 examples of different antibiotic groups which may trigger B Lactam allergy
- Penicillins: natural (G) and synthetic (V)
- Penicillinase-resistant (fluclox)
- Aminopenicillins (Amoxicillin)
- Monobactams
- Carbopenems
- Cephalosporins
If a patient has a history of immediate DHR to penicillin what must you consider?
Potential cross reactivity between B Lactam groups, include this in risk management
What is guidance on choosing an alternative to penicillin in the context of a known DHR ?
- If B lactam is needed and clinical risk is low, cephalosporin is reasonable
- cross reactivity with 2nd/3rd gen cephs is very low
- if clinical risk is high, seek advice
- oral test dose may be possible (safer than IV), seek advice from seniours
