Allergic reactions to drugs and anaphylaxis

Question 1

What is type I hypersensitivity

Answer 1

IgE mediated-drug hypersensitivity

Question 2

How does type I hypersensitivity relate to acute anaphylaxis

Answer 2

1. Prior exposure to antigen/drug
2. IgE antibodies formed after exposure to molecule
3. IgE becomes attached to mast cells or leucocytes, expressed as cell surface receptors
4. Re-exposure causes mast cell degranulation and release of pharmacologically active substances

Question 3

How long does anaphylaxis last for

Answer 3

1-2 hours

Question 4

What is anaphylaxis

Answer 4

1. Vasodilation
2. Increased vascular permeability
3. Bronchoconstrcition
4. Urticaria
5. Angio-oedema

Question 5

What are type II reactions

Answer 5

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

Question 6

What are type III reactions

Answer 6

1. Antigen and antibody form large complexes and activate complement
2. Small blood vessels are damaged or blocked
3. Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process

Question 7

Example of type III reactions

Answer 7

Glomerulonephritis

Vasculitis

Question 8

What are type IV reactions

Answer 8

Antigen-specific receptors develop on T-lymphocyte

Question 9

What are non-immune anaphylaxes caused by

Answer 9

Direct mast cell degranulation caused by some drugs

Question 10

What is anaphylactic shock

Answer 10

Hypotension

Question 11

Main features of anaphylaxis

Answer 11

1. Exposure to drug
2. Rapid
3. Swelling of lips, face, oedema and central cyanosis
4. Wheeze

Question 12

How is anaphylaxis managed

Answer 12

1. ABC
2. Stop drug if infusion
3. Adrenaline IM 500mcg (300mcg epi-pen)
4. High flow oxygen
5. IV antihistamine
6. IV Hydrocortison

Question 13

Example of anti-histamine used when treating anaphylaxis

Answer 13

Chlorphenamine (10mg)

Question 14

How much Hydrocortisone is used

Answer 14

100-200 mg

Question 15

What medicinal factor increases risk for hypersensitivity

Answer 15

1. Protein or polysaccharide-based macro molecules

Question 16

What host factors contribute to hypersensitivity

Answer 16

1. Females > Males

2. Immunosuppression

Question 17

What genetic factors increase risk of hypersensitivity

Answer 17

1. Certain HLA groups

Question 18

Three drugs that commonly cause anaphylaxis

Answer 18

Penicillin
Aspirin
NSAIDs

Question 19

How common are penicillin allergies

Answer 19

2%

Question 20

What should we do if we see someone on the street undergoing an anaphylactic reaction s

Answer 20

1. ABCDE
A - airways
B - Breathing
C- Circulation 
D - Disability
E - Exposure 

2. Diagnosis
   Look for: Acute onset of illness
3. Call for help
4. Lie patient flat and raise legs
5. Adrenaline
6. The other hard stuff

Question 21

Clinical criteria for being ‘allergic’ to a drug

Answer 21

1. Does not correlate with drug properties
2. No linear relation to dose
3. Induction period on primary exposure
4. Disappearance on cessation
5. Re-appears on re-exposure
6. Occurs in a minority of patients

Question 22

What cells secrete IgE

Answer 22

1. Eosinophils
2. Basophils
3. Mast Cells

Question 23

Why do we need basophils when we have mast cells

Answer 23

Mast cells can only reside in tissues - cannot circulate

Question 24

What does mast cell require for division

Answer 24

CD117 (c-kit)

Question 25

What makes an allergen

Answer 25

1. Presence of PAMPs

Question 26

Clinical presentation of Anaphylaxis

Answer 26

1. ABCDE 2. Elevated serum tryptase and histamine levels 3. Vasodilation, flushing and lower BP 4. Bronchial SM contraction (SOB) 5. Skin Rash and swelling (mastocytosis) 6. Urticaria 7. Angio-oedema Takes 1-2 hours EVENTUALLY: Pain and vomiting

Question 27

Treatment of allergic reactions

Answer 27

1. Increase dose of antigen (sub lingually) - ectopic eczema (not asthma) 2. 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: 1. Sodium Cromoglycate (mast cell stabilisers, reduces mediator release) 2. Salmeterol 3. Prednisololne 4. MAP kinase inhibitors 5. Calcium channel blockers ``` Finally: H1 antagonists Montelukast - leucotrienes Trypatase Inhibitors PAR-2 antagonists ```

Question 28

treatment of anaphylaxis

Answer 28

1. 0.15mg/0.3mg IM adrenaline Beta-2: Causes bronchodilaition Myocardial contraction Inhibition of mast cells Alpha-1: 1. Peripheral vasoconstriction 2. Reduces oedema High Flow Oxygen IV Fluids Antihistamine (Chlorphenamine 10mg) IV Hydrocortisone (100-200mg)

Question 29

What is non-immune anaphylaxis

Answer 29

1. Due to direct mast cell degranulation

Question 30

What is anaphylactic shock

Answer 30

Hypotension