Anaphylaxis And Drug Allergy

Question 1

Clinical indications related to allergy

Answer 1

Epithelial - swelling, eczema, itching, reddening
Airways - Excessive mucus production, bronchoconstrcition
GI - Abdominal bloating, vomiting, diarrhoea
Anaphylaxis - airway, breathing, circulation

Question 2

Allergy definition

Answer 2

Abnormal response to harmless foreign material

Question 3

Atopy definition

Answer 3

Tendency to develop allergies

Question 4

Pathogenesis of allergy

Answer 4

Usually involved IgE, IgG4, IgA
Cells involved - mast cells, eosinophils, basophils
Mediators - cytokines, chemokines, lipids, small molecules

Question 5

Hypersensitivity defintion

Answer 5

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

Question 6

Drug hypersensitivity

Answer 6

Immediate > 1hr (urticarial, anaphylaxis)
Delayed > 1hr (other rashes, hepatitis, cytopenia’s)

Question 7

Types of hypersensitivity reactions

Answer 7

Type 1 - IgE hypersensitivity
Type 2 - IgG mediated cytotoxicity
Type 3 - Immune complex deposition
Type 4 - T cell mediated

Question 8

Type 1 hypersensitivity reaction

Answer 8

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

Question 9

Type 2 hypersensitivity reaction

Answer 9

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

Question 10

Type 3 hypersensitivity reaction

Answer 10

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

Question 11

Type 4 hypersensitivity reaction

Answer 11

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)

Question 12

What is non-immune anaphylaxis

Answer 12

Due to direct mast cell degranulation
Some drugs recognised to cause this
No prior exposure
Clinically identical

Question 13

Anaphylaxis main features

Answer 13

Exposure to drug
Immeadiate rapid onset
Rash
Swelling of lips, oedema, central cyanosis
Wheeze/SOB
Hypotension
Cardiac arrest

Question 14

Management of anaphylaxis

Answer 14

Adrenaline IM 500mg
High flow oxygen
IV fluids
IV antihistamine (chlorophenamine 10mg)
IV hydrocortisone (100-200mg)

Question 15

ABCDE

Answer 15

Airway
Breathing
Circulation
Disability
Exposure

Question 16

Adrenaline pathways

Answer 16

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

Question 17

Risk factors for hypersensitivity

Answer 17

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

Question 18

Clinical criteria for allergy to drug

Answer 18

• 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