Anaphylaxis And Drug Allergy Flashcards
Clinical indications related to allergy
Epithelial - swelling, eczema, itching, reddening
Airways - Excessive mucus production, bronchoconstrcition
GI - Abdominal bloating, vomiting, diarrhoea
Anaphylaxis - airway, breathing, circulation
Allergy definition
Abnormal response to harmless foreign material
Atopy definition
Tendency to develop allergies
Pathogenesis of allergy
Usually involved IgE, IgG4, IgA
Cells involved - mast cells, eosinophils, basophils
Mediators - cytokines, chemokines, lipids, small molecules
Hypersensitivity defintion
Objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects and may be caused by immunologic (allergic) and non-immunological mechanisms
Drug hypersensitivity
Immediate > 1hr (urticarial, anaphylaxis)
Delayed > 1hr (other rashes, hepatitis, cytopenia’s)
Types of hypersensitivity reactions
Type 1 - IgE hypersensitivity
Type 2 - IgG mediated cytotoxicity
Type 3 - Immune complex deposition
Type 4 - T cell mediated
Type 1 hypersensitivity reaction
Acute anaphylaxis
- Prior exposure to the antigen/drug
- IgE antibodies formed after exposure to molecule
- IgE becomes attached to mast cells degranulation and release of pharmacologically active substances such as histamine, prostaglandins, leukotrienes, platelet activating factor
Type 2 hypersensitivity reaction
Antibody dependant cytotoxicity
- Drug or metabolite combines with protein
- Body treats it as foreign protein and forms antibodies (IgG, IgM)
- Antibodies combine with the antigen and complement activation damages the cells e.g. methyl-dopa-induced haemolytic anaemia pemphigus
Type 3 hypersensitivity reaction
Immune complex mediated
- Antigen and antibody form large complexes and activate complement
- Small blood vessels are damaged or blocked
- Leukocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process
- Includes glomerulonephritis vasculitis
Type 4 hypersensitivity reaction
Lymphocyte mediated
- Antigen specific receptors develop on T-lymphocytes
- Subsequent administration leads to locals or tissue allergic reaction
- E.g contact dermatitis
- E.g Steven Johnson Syndrome (TEN)
What is non-immune anaphylaxis
Due to direct mast cell degranulation
Some drugs recognised to cause this
No prior exposure
Clinically identical
Anaphylaxis main features
Exposure to drug
Immeadiate rapid onset
Rash
Swelling of lips, oedema, central cyanosis
Wheeze/SOB
Hypotension
Cardiac arrest
Management of anaphylaxis
Adrenaline IM 500mg
High flow oxygen
IV fluids
IV antihistamine (chlorophenamine 10mg)
IV hydrocortisone (100-200mg)
ABCDE
Airway
Breathing
Circulation
Disability
Exposure
Adrenaline pathways
Increases peripheral vascular resistance increased bp and coronary perfusion via alpha-1-adrenoreceptors
Stimulation of beta-1 adrenoreceptors positive inotropic and chronotropic effects on heart
Reduces oedema and bronchodilators via beta-2-adrenoreceptors
Attenuates further release of mediators from mast cells and basophils by increasing intracellular c-AMP and so reducing the release of inflammatory mediators
Risk factors for hypersensitivity
Medicine factors - protein or polysaccharide based macro molecules
Host factors
- females
- EBV,HIV
- Previous drug reactions
- Uncontrolled asthma
Genetic factors
- Certain HLA groups
- Acetylator status
Clinical criteria for allergy to drug
- Does not correlate with pharmacological properties of the drug
- No linear relation with dose (tiny dose can cause severe effects)
- Reaction similar to those produced by other allergens
- Induction period of primary exposure
- Disappearance on cessation
- Re-appears on re-exposure
- Occurs in a minority of patients on the drug
