Anaphylaxis

Question 1

What is an allergic reaction?

Answer 1

Interaction of drug/metabolite/or non drug element with patient and disease with subsequent re-exposure.

Question 2

Can the exposure be non-medical?

Answer 2

Yes - i.e. penicillin in dairy products.

Question 3

What are the target organs of allergy?

Answer 3

Skin
Respiratory tract
GIT
Blood and BVs

Question 4

What are the most common drugs that cause allergic reactions?

Answer 4

ABx and NSAIDs/aspirin

Question 5

Is intolerance the same as allergy?

Answer 5

No

Question 6

Drug hypersensitivity

Answer 6

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

Question 7

Immediate v delayed hypersensitivity

Answer 7

Immediate <1hr (urticarial, anaphylaxis)
Delayed >1hr (other rashes, hepatitis, cytopenias)

Question 8

How many types of hypersensitivity reactions are there?

Answer 8

4

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

Question 9

Type 1 hypersensitivity - acute anaphylaxis.

Answer 9

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.

Question 10

Anaphylaxis characteristics

Answer 10

Occurs within minutes and lasts 1-2 hours.

Vasodilation .

Increased vascular permeability.

Bronchoconstriction.

Urticaria.

Angio-oedema.

Drug anaphylaxis majority of deaths due to anaphylaxis.

Insect venom most common cause followed by medications.

1-20% have biphasic response

Question 11

Type 2 reactions - AB dependent cytotoxicity

Answer 11

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.

Question 12

Type 3 reactions - immune complex mediated

Answer 12

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.

Question 13

Type 4 reactions - lymphocyte mediated

Answer 13

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)

Question 14

Drugs commonly implicated in hypersensitivity reactions

Answer 14

Aspirin
Penicillin and cephalosporins
Sulfonamides

Question 15

Non-immune anaphylaxis

Answer 15

Previously called Anaphylactoid reactions
Due to direct mast cell degranulation.
Some drugs recognised to cause this
No prior exposure
Clinically identical

Question 16

What are the main features of anaphylaxis?

Answer 16

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
20 deaths per year in the UK

Question 17

Management of anaphylaxis

Answer 17

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 as first line.

Question 18

Adrenaline

Answer 18

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.

Question 19

What are the risk factors for hypersensitivity?

Answer 19

Medicine factors:
Protein or polysacharide based macro molecules

Host factors:
Females > Males – we don’t know why
EBV, HIV
Prev drug reactions
Uncontrolled asthma

Genetic factors:
Certain HLA groups
Acetylator status

Question 20

What are the clinical criteria for allergy to drug?

Answer 20

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

Question 21

Assessment using the ABCDE approach - D?

Answer 21

Disability
*dizziness, decreased conscious level or loss of consciousness

Question 22

Assessment using the ABCDE apprach - E?

Answer 22

Exposure - flushed, itchy, urticaria or hives, angioedema.

Question 23

Assessment using the ABCDE approach - A?

Answer 23

Airways - hoarse voice, stridor

Question 24

Assessment using the ABCDE approach - B?

Answer 24

Increased work of breathing, wheeze, fatigue, cyanosis, SpO2 <94%

Question 25

Assessment using the ABCDE approach - C?

Answer 25

Circulation - low BP, signs of shock, confusion, reduced consciousness.

Question 26

Removing trigger and positioning

Answer 26

Remove trigger if possible.
Lie PT flat (legs elevated or not)
- Sitting might make breathing easier
- If pregnant - lie on left side.

Question 27

IM dosing of adrenaline

Answer 27

Use adrenaline at 1 mg/mL (1:1000) concentration

Adult and child > 12 years: 500 micrograms IM (0.5 mL)

Child 6-12 years: 300 micrograms IM (0.3 mL)

Child 6 months to 6 years: 150 micrograms IM (0.15 mL)

Child <6 months: 100-150 micrograms IM (0.1-0.15 mL)

Question 28

Refractory anaphylaxis defined as?

Answer 28

Anaphylaxis requiring ongoing treatment (due to persisting respiratory or cardiovascular symptoms) despite 2 appropriate doses of IM adrenaline.

Question 29

Investigations of anaphylaxis

Answer 29

As for a medical emergency:
12-lead ECG
Chest x-ray
urea and electrolytes
blood gases

mast cell tryptase