anaphylaxis and drug allergy

Question 1

define hypersensitivity

Answer 1

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 2

is anaphylaxis immunological or not?

Answer 2

can be or can be non immunological

Question 3

what are the two types of drug hypersensitivity

Answer 3

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

Question 4

what are the types of hypersensitivity

Answer 4

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

Question 5

describe type 1 hypersensitivity

Answer 5

IgE mediated drug hypersensitivity
Acute anaphylaxis
Prior exposure to the antigen

Question 6

what does re-exposure of antigen cause with type 1 IgE

Answer 6

Re-exposure causes mast cell degranulation and release of pharmacologically active substances

Question 7

how does IgE work

Answer 7

IgE becomes attached to mast cells or leukocytes, expressed as cell surface receptors

Question 8

describe anaphylaxis

Answer 8

occurs within minutes- lasts 1-2 hours
vasodilation
increased vascular permeability
bronchoconstriction
urticaria
angio-oedema

Question 9

describe type 2 hypersensitivity

Answer 9

IgG mediated cytotoxicity
Antibody dependent cytotoxicity
Drug or metabolite combines with a protein

Question 10

how does IgG work

Answer 10

Body treats it as a foreign protein and forms antibodies
Antibodies combine with the antigen and complement activation damages the cells

Question 11

describe type 3 hypersensitivity

Answer 11

immune complex deposition
Immune complex mediated
Small blood vessels are damaged or blocked

Question 12

how does type 3 work?

Answer 12

Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process

Question 13

describe type 4 hypersensitivity

Answer 13

T cell mediated
Lymphocyte mediated
Antigen specific receptors develop on T-lymphocytes
Subsequent administration

Question 14

what do type 4 reactions lead to?

Answer 14

leads to local or tissue allergic reactions

Question 15

define anaphylaxis

Answer 15

an acute allergic reaction to an antigen to which the body has become hypersensitive

Question 16

what is non immune anaphylaxis due to?

Answer 16

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

Question 17

what are the main signs of anaphylaxis?

Answer 17

immediate rapid onset
rash
swelling of lips, face, oedema, central cyanosis
wheeze
hypotension
cardiac arrest

Question 18

how is anaphylaxis managed?

Answer 18

more important-
Commence basic life support
Adrenaline – IM 500µg
High flow oxygen

less important-
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

Question 19

what is the effect of adrenaline?

Answer 19

1.vasoconstriction
2.Stimulation of beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart
3.Reduces oedema and bronchodilates via beta2-adrenoceptors

Question 20

what does adrenaline- vasoconstriction do?

Answer 20

increase in peripheral vascular resistance, increased BP and coronary perfusion

Question 21

what are the risk factors for hypersensitivity?

Answer 21

medicine factors
host factors
genetic factors

Question 22

medicine risk factors for hypersensitivity

Answer 22

Protein or polysacharide based macro molecules

Question 23

host factors risk factors for hypersensitivity

Answer 23

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

Question 24

genetic factors for risk factors for hypersensitivity

Answer 24

Certain HLA groups
Acetylator status

Question 25

what are the clinical criteria for allergy to drugs?

Answer 25

1. Does not correlate with pharmacological properties of the drug
2. No linear relation with dose (tiny dose can cause severe effects)
   3.Reaction to similar to those produced by other allergens
   4.Induction period of primary exposure
   5.Disappearance on cessation