Allergic Reactions To Drugs And Anaphylaxis 20.11.23 Flashcards
Hypersensitivity is broadly defined as
‘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‐immunologic mechanisms’
Can anaphylaxis be immunological or non-immunological or one one?
It can be both
What drug hypersensitivities are immediate and which are delayed?
Immediate <1hr (urticarial, anaphylaxis)
Delayed >1hr (other rashes, hepatitis, cytopenias)
What are the 4 types of hypersensitivity?
Type 1 – IgE mediated drug hypersensitivity
Type 2 – IgG mediated cytotoxicity
Type 3 – Immune complex deposition
Type 4 – T cell mediated
What happens in type 1 hypersensitivity?
Prior exposure to the 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 such as histamine, prostaglandins, leukotrienes, platelet activating factor etc
What happens during anaphylaxis?
Vasodilation
Increased vascular permeability
Bronchoconstriction
Urticaria (hives)
Angio-oedema (swelling of lower level of skin)
Drug anaphylaxis majority of deaths due to anaphylaxis
Insect venom most common cause followed by medications
1-20% have biphasic response
What happens in type 2 hypersensitivity?
Drug or metabolite combines with a 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
What happens in type 3 hypersensitivity?
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
Includes glomerulonephritis, vasculitis,
What happens in type 4 hypersensitivity?
Antigen specific receptors develop on T-lymphocytes
Subsequent admin, adminstration leads to local or tissue allergic reaction
E.g. contact dermatitis
E.g. Stevens Johnson syndrome (TEN)
What is non immune anaphylaxis?
Previously called Anaphylactoid reactions
Due to direct mast cell degranulation.
Some drugs recognised to cause this
No prior exposure
Clinically identical
What is the management of anaphylaxis?
Commence basic life support. ABC
Stop the drug if infusion
Adrenaline IM 500micrograms(300mcg epi-pen)
High flow oxygen
IV fluids – aggressive fluid resuscitation
If anaphylactic shock may need IV adrenaline with close monitoring
Antihistamines not first line treatment but can be used for skin symptoms
Corticosteroids no longer recommended
What does adrenaline do?
Vasoconstriction - increase in peripheral vascular resistance, increased BP and coronary perfusion via alpha1-adrenoceptors
Stimulation of Beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart
Reduces oedema and bronchodilates via beta2-adrenoceptors
Attenuates further release of mediators from mast cells and basophils by increasing intracellular c-AMP and so reducing the release of inflammatory mediators
What are the 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
