Hypersensitivity to Antibiotics

Question 1

What is Steven-Johnson syndrome?

Answer 1

A bullous form of erythema multiforme that may be extensive and involve mucous membrane/large areas of the body (red splotchy rash)

Question 2

What are predictable adverse reactions to a drug?
Is it dose-dependent or independent?
Who does it affect?

Answer 2

1. dose-dependent
2. Related to pharmacology of drug
3. Occurs in “normal patients”

Ex. side effects, toxicity, drug interactions

Question 3

What are unpredictable adverse drug reactions?
Is it dose-dependent or independent?
Who does it affect?

Answer 3

1. Dose Independent (even a little bit can react)
2. no related to pharacology
3. Occurs in susceptible patients (immunocompromised)

Idiosyncratic, allergic or pseudoallergic reactions

Question 4

What is a pseudoallergy?

What is a common cause?

Answer 4

It clinically looks like an allergic reaction (anaphylaxis) but it is not IgE specific. It is a generalized, non-specific response caused by mast cell degranulation.

A common cause is contrast dye.

Question 5

Why is the initial course of therapy uneventful in drug allergies?

Answer 5

Because this is when sensitization is occuring and IgE antibodies are being made to sit on the mast cells.
The response may take several treatment days to develop

Question 6

An allergic person will react at a dose ___________________________ and the reaction can be reproduced by ______________________.

Answer 6

Far below the therapeutic index and can be reproduced by readministering a SMALL amount of drug

Question 7

What cell is a prime indicator that an allergic reaction/hypersensitivity is occuring?

Answer 7

Eosinophils

Question 8

What is a likely explanation if the allergic reaction persists even after the medication is stopped?

Answer 8

Antigen from the drug may have been taken up by tissue and is being slowly released or it is bound to serum proteins

Question 9

What are the four types of hypersensitivities?

Answer 9

1. Immediate (IgE, mast cell, histamine, ECF)
2. Ab-mediated (goodpasture’s, hemolysis)
3. Ab-Antigen complex (Lupus, serum sickness, polyarteritis nodosa)
4. T-cell mediated (MS, diabetes, etc)

Question 10

Why is classification of drug reactions so hard?

Answer 10

You do not know the mechanism of action responsible for the symptoms.
They are uncommon, unpredictable and cannot be reproduced in animals

Question 11

What is the “hapten hypothesis”?

Answer 11

Univalent “haptens” cannot elicit an immune response. Cross-linking must occur so the drug can be bioactivated.
Drug metabolism detoxifies the active metabolite via:
1. redox, hydrolysis
2. conjugation

Question 12

What are the two phases of drug metabolism?

Answer 12

1. redox, hydrolysis

2. conjugation

Question 13

What are the steps in drug allergy diagnosis?

Answer 13

1. History
2. In vivo skin testing
3. In vitro testing (Never Used)
4. Tryptase drug challenge

Question 14

What compounds can in vivo skin tests be done with?

Answer 14

1. Large molecular weight compounds - foreign antisera, hormones, enzymes, toxoid, egg-vaccines
2. Penicillin

All other Antibiotics should not be used for skin test because they are haptenogenic

Question 15

What is tryptase?

Answer 15

A selective marker for mast cells that is stored in granules of the mast cell and are released when it degranulates.
The B-tryptase lingers for 1-2 hours so elevated levels can be measured in anaphylactic response.

It is measured instead of histamine because histamine is really short acting

Question 16

What is a provocative drug challenge?

Answer 16

It is not to be done with severe allergy, but with moderate allergy you can give 1/100 then 1/10, then the full dose
This lets you see how much drug the patient can tolerate

Question 17

If your patient has hives, what type of hypersensitivity is likely?
What if they have maculopapular spotS?
What if they have burns, bollous, etc?

Answer 17

Hives = IgE mediated type 1
Maculopapular = type 4 usually
Severe= mechanism unsure DO NOT USE DRUG

Question 18

What is desensitization?
What is the time course?
What should be available while you are performing it?

Answer 18

The conversion of a drug-allergic person from highly sensitive to a state where the drug is tolerated.
Administer incremental dose over hours to days.

You should have epi, peak flow cytometer handy in case anaphylaxis occurs. Take BP before

Question 19

Who should desensitization be performed on?

Answer 19

1. Patients with IgE antibodies to a particular drug and there is NO ALTERNATIVE drug
2. IgE sensitivity ONLY