Allergic reactions to drugs and anaphylaxis Flashcards
What is an allergic reaction to a drug?
- Interaction of drug/metabolite/or non drug element with patient and disease
- Subsequent re-exposure
Define hypersensitvity
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
What is defined as an immediate hypersensitivity reaction?
<1hr (urticarial, anaphylaxis)
What is defined as a delayed hypersensitivity reaction?
> 1hr (other rashes, hepatitis, cytopenias)
Describe type 1 hypersensitvity
- 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
Describe physiology of anaphylaxis
- Occurs within minutes and lasts 1-2 hours
- Vasodilation
- Increased vascular permeability
- Bronchoconstriction
- Urticaria (hives)
- Angio-oedema
- Drug anaphylaxis majority of deaths due to anaphylaxis
- Insect venom most common cause followed by medications
- 1-20% have biphasic response
- Happens again
Describe type 2 hypersensitivity reaction
- Antibody dependant cytotoxicity
- 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
Describe type 3 hypersensitivity reaction
- immune complex mediated
- 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
Describe type 4 hypersensitivity reaction
T cell and Lymphocyte mediated
- Antigen specific receptors develop on T-lymphocytes
- Subsequent administration leads to local or tissue allergic reaction
- E.g. contact dermatitis (can be from plaster)
- E.g. Stevens Johnson syndrome (TEN)
Define anaphylaxis
an acute allergic reaction to an antigen to which the body has become hypersensitive
Give the main features of anaphylaxis
- Exposure to drug, immediate rapid onset
- Rash (absent in 10-20%)
- Swelling of lips, face, oedema, central cyanosis
- Wheeze / SOB
- Hypotension (Anaphylactic shock)
- Cardiac Arrest
How would you manage anaphylaxis?
● Commence basic life support
● Adrenaline – IM 500µg
● High flow oxygen
If a person has mild, localised skin symptoms and or swelling of lips face but not problems with ABC (airways, breathing, circulation) is this anaphylaxis?
No
What determines whether a reaction is anaphylaxis?
Whether they have problems with ABC
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
