Allergic reactions to drugs and anaphylaxis Flashcards
What is type I hypersensitivity
IgE mediated-drug hypersensitivity
How does type I hypersensitivity relate to acute anaphylaxis
- Prior exposure to antigen/drug
- IgE antibodies formed after exposure to molecule
- IgE becomes attached to mast cells or leucocytes, expressed as cell surface receptors
- Re-exposure causes mast cell degranulation and release of pharmacologically active substances
How long does anaphylaxis last for
1-2 hours
What is anaphylaxis
- Vasodilation
- Increased vascular permeability
- Bronchoconstrcition
- Urticaria
- Angio-oedema
What are type II reactions
Drug metabolite combines with a protein and body treats it as a foreign protein, making antibodies against it
Antibodies combine with antigen and complement activation damaged the cell
What are type III reactions
- Antigen and antibody form large complexes and activate complement
- Small blood vessels are damaged or blocked
- Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process
Example of type III reactions
Glomerulonephritis
Vasculitis
What are type IV reactions
Antigen-specific receptors develop on T-lymphocyte
What are non-immune anaphylaxes caused by
Direct mast cell degranulation caused by some drugs
What is anaphylactic shock
Hypotension
Main features of anaphylaxis
- Exposure to drug
- Rapid
- Swelling of lips, face, oedema and central cyanosis
- Wheeze
How is anaphylaxis managed
- ABC
- Stop drug if infusion
- Adrenaline IM 500mcg (300mcg epi-pen)
- High flow oxygen
- IV antihistamine
- IV Hydrocortison
Example of anti-histamine used when treating anaphylaxis
Chlorphenamine (10mg)
How much Hydrocortisone is used
100-200 mg
What medicinal factor increases risk for hypersensitivity
- Protein or polysaccharide-based macro molecules
What host factors contribute to hypersensitivity
- Females > Males
2. Immunosuppression
What genetic factors increase risk of hypersensitivity
- Certain HLA groups
Three drugs that commonly cause anaphylaxis
Penicillin
Aspirin
NSAIDs
How common are penicillin allergies
2%
What should we do if we see someone on the street undergoing an anaphylactic reaction s
1. ABCDE A - airways B - Breathing C- Circulation D - Disability E - Exposure
- Diagnosis
Look for: Acute onset of illness - Call for help
- Lie patient flat and raise legs
- Adrenaline
- The other hard stuff
Clinical criteria for being ‘allergic’ to a drug
- Does not correlate with drug properties
- No linear relation to dose
- Induction period on primary exposure
- Disappearance on cessation
- Re-appears on re-exposure
- Occurs in a minority of patients
What cells secrete IgE
- Eosinophils
- Basophils
- Mast Cells
Why do we need basophils when we have mast cells
Mast cells can only reside in tissues - cannot circulate
What does mast cell require for division
CD117 (c-kit)
What makes an allergen
- Presence of PAMPs
Clinical presentation of Anaphylaxis
- ABCDE
- Elevated serum tryptase and histamine levels
- Vasodilation, flushing and lower BP
- Bronchial SM contraction (SOB)
- Skin Rash and swelling (mastocytosis)
- Urticaria
- Angio-oedema
Takes 1-2 hours
EVENTUALLY: Pain and vomiting
Treatment of allergic reactions
- Increase dose of antigen (sub lingually) - ectopic eczema (not asthma)
- Stop IgE production:
IL-4 antagonist (Pitakinra)
Lumiliximab (CD23 antibodies) - leukaemia
————————-
Anti-IgE therapy in atopic individuals:
Omalizumab inhibits binding of IgE to receptor on mast cells
Anti-cytokine antibodies:
Infliximab
IL-5 antibody (Mepolizumab) - asthma
Mast Cell inhibitors:
- Sodium Cromoglycate (mast cell stabilisers, reduces mediator release)
- Salmeterol
- Prednisololne
- MAP kinase inhibitors
- Calcium channel blockers
Finally: H1 antagonists Montelukast - leucotrienes Trypatase Inhibitors PAR-2 antagonists
treatment of anaphylaxis
- 0.15mg/0.3mg IM adrenaline
Beta-2:
Causes bronchodilaition
Myocardial contraction
Inhibition of mast cells
Alpha-1:
- Peripheral vasoconstriction
- Reduces oedema
High Flow Oxygen
IV Fluids
Antihistamine (Chlorphenamine 10mg)
IV Hydrocortisone (100-200mg)
What is non-immune anaphylaxis
- Due to direct mast cell degranulation
What is anaphylactic shock
Hypotension