Anaphylaxis and drug allergy

Question 1

What are the target organs of allergy?

Answer 1

skin
resp tract
GIT
blood and blood vessels

Question 2

What is the pathophysiology behind anaphylaxis?

Answer 2

vasodilation - flushed
increased vascular permeability - oedema
bronchoconstriction - wheezing 
urticaria 
angioedema

Question 3

In terms of antibodies and Ag explain type 1 hypersensitivity

Answer 3

1. prior exposure to the antigen/ drug
2. IgE Ab formed after prior exposure attach to mast cells and are now receptors for Ag
3. re-exposure causes mast cell degranulation and release of histamine

Question 4

In terms of antibodies and Ag explain type 2 hypersensitivity

Answer 4

1. drug or metabolite combines with a protein
2. body treats it as a foreign protein and forms AB eg IgG and IgM
3. Abs combine with the Ag and complement activation damages the cells

Question 5

In terms of antibodies and Ag explain type 3 hypersensitivity

Answer 5

1. Ag and Ab form large complexes and activate complement
2. small blood vessels become damaged or blocked (vasculitis)
3. leukocytes attracted to the site of the reaction release pharmacologically active substances leading to inflammation

Question 6

In terms of Ags explain type 3 hypersensitivity

Answer 6

1. Ag specific receptors develop on T cells

2. subsequent administration leads to local or tissue allergic reaction

Question 7

What is non-immune anaphylaxis due to?

Answer 7

direct mast cells degranulation without prior exposure

Question 8

What are the main clinical features of anaphylaxis?

Answer 8

immediate, rapid onset of:
rash
swelling of lips, face, oedema, central cyanosis
wheeze/ SOB
hypotension (shock)
cardiac arrest

Question 9

How is anaphylaxis managed?

Answer 9

ABC (basic life support)
stop the drug 
ADRENALINE IM 500µg (300µ epipen)
high flow oxygen
IV fluids
IV anti-histamine
IV hydrocortisone 
(If anaphylactic shock may need IV adrenaline and close monitoring)

Question 10

What does adrenaline do?

Answer 10

vasoconstriction to increase BP and coronary perfusion ( via alpha 1 adrenoceptors)
stimulation of beta 1 adrenoceptors giving positive ionoptropic and chronotropic effects
reduces oedema
bronchodilation via beta 2 receptors
reduces further release of inflammatory mediators from mast cells and basophils by increasing intracellular cAMP

Question 11

What are the risk factors for hypersensitivity?

Answer 11

protein or polysaccharide based macromolecules
gender (W>M)
immunosuppresion
certain HLA groups

Question 12

What are the common drugs causing anaphylaxis?

Answer 12

penicillin
aspirin
NSAIDs

Question 13

What are the clinical criteria for allergy to a drug?

Answer 13

does not correlate with the pharmacological properties of the drug
no linear relation with dose (small dose can cause severe effects)
reaction produced similar to that produced by other allergens
induction period of primary exposure
disappearance on cessation
reappearance on re-exposure
occurs in minority of pts on the drug