Primer

Question 1

What is a Type A Adverse Drug Reaction?

Answer 1

Predictable: Usually dose dependent, related to the known pharmacologic actions of the drug, and occur in otherwise healthy subjects. Predictable reactions account for about 80% of all ADRs and are subdivided into overdose, side effects, secondary effects, and drug interactions.

Question 2

What is a Type B Adverse Drug Reaction?

Answer 2

Unpredictable: Unpredictable reactions are sub- divided into drug intolerance (an undesirable pharmacologic effect that occurs at low and sometimes subtherapeutic doses of the drug without underlying abnormalities of metabolism,
excretion, or bioavailability of the drug), drug idiosyncrasy (abnormal and unexpected effect, usually caused by underlying abnormalities of metabolism, excretion, or bioavailability), drug allergy (immunologically mediated ADRs [including IgE-mediated drug allergy]), and pseudoallergic reactions (also called anaphylactoid reactions, which are due to direct release of mediators from mast cells and basophils rather than IgE antibodies).

Question 3

Type IV reactions?

Answer 3

Type IV reactions can be subdivided into 4 categories involving activation and recruitment of monocytes (type IVa), eosinophils (type IVb), CD4+ or CD8+ T cells (type IVc), and neutrophils (type IVd).

Question 4

What are symptoms of DRESS?

Answer 4

Cutaneous eruption, fever, eosinophilia, hepatic dysfunction, lymphadenopathy

Question 5

What is DRESS?

Answer 5

cutaneous, drug-induced, multiorgan inflammatory response that can be life-threatening; DRESS is atypical from other drug-induced allergic reactions in that the reaction develops later, usually 2 to 8 weeks after therapy is started; symptoms can worsen after the drug is discontinued; and symptoms can persist for weeks or even months after the drug has been discontinued.

Question 6

Another name for serum mature tryptase?

Answer 6

Beta-tryptase

Question 7

When is best time to get tryptase?

Answer 7

30min-2hrs after reaction

Question 8

What is half life of tryptase?

Answer 8

2 hours

Question 9

What is drug tolerance?

Answer 9

a state in which a patient with drug allergy will tolerate a drug without adverse reaction. Does not necessarily need to be for IgE-mediated.

Question 10

When should graded challenge (or induction of drug tolerance) should almost never be performed if the reaction history is consistent with?

Answer 10

if the reaction history is consistent with a severe non–IgE-mediated reaction, such as SJS, TEN, DRESS, hepatitis, or hemolytic anemia.

Question 11

What is the NPV of PCN skin testing?

Answer 11

Approaches 100%

Question 12

What is the major determinant of penicillin?

Answer 12

Penicilloyl

Question 13

What are penicilloate and pennilloate?

Answer 13

Minor antigenic determinants

Question 14

allergic cross-reactivity between penicillin and carbapenems are similar to?

Answer 14

penicillin/cephalosporins

Question 15

Whats the most common cause of SJS and TEN?

Answer 15

Sulfonamides

Question 16

Which part of Sulfonamide antibiotics is critical for the development of delayed reactions?

Answer 16

The N4 aromatic amine is critical for the development of delayed reactions to sulfonamide antibiotics (through oxidation to hydroxyamines and nitroso compounds), Because nonantibiotic sulfonamides lack these structural components, they would not be expected to cross-react with sulfonamide antibiotics. Several clinical studies demonstrated no increased risk of reactions to nonantibiotic sulfonamides in patients with a history of allergy to sulfonamide antibiotics

Question 17

Which part of Sulfonamide antibiotics is critical for the development of IgE mediated reactions?

Answer 17

N1 substituted ring

Question 18

Most adverse reactions to local anesthestics are due to what?

Answer 18

Non allergic factors (ie vasovagal, anxiety, inadvertent IV Epi)

Question 19

Benzoate esters and patch testing?

Answer 19

There is cross reactivity among benzoate esters (not among amides)

Question 20

Risk factors to anaphylactoid reaction to RCM?

Answer 20

Female, asthma, and h/o previous anaphylactoid reaction to RCM; also more serious included B-blocker, CV conditions or both

Question 21

What is the pathogenesis of RCM reactions?

Answer 21

Degranulation and systemic mediator release

Question 22

What is the incidence of cough from ACE-I?

Answer 22

5-35% (cause unclear-maybe bradykinin or substance P)

Question 23

What is the incidence of angioedema from ACE-I?

Answer 23

1 to 7/1000

Question 24

What does ACE-I induced angioedema usually effect?

Answer 24

head and neck, esp lips. Rarely urticaria and pruritus

Question 25

What is the prominent mediator in ACE-induced AE and hereditary AE?

Answer 25

Bradykinin

Question 26

ACE-I are C/I in which patients?

Answer 26

Those with HAE

Question 27

What is the pathophysiology of AERD?

Answer 27

excessive production of cysteinl leukotrienes, increased numbers of inflammatory cells expressing cysteinyl leukotriene 1 receptors, and greater airway responsiveness to cysteinyl leukotrienes.

Question 28

What happens with ASA administration in AERD?

Answer 28

leads to inhibition of COX-1, with a resultant decrease in prostaglandin E2 levels. Prostaglandin E2 normally inhibits 5-lipoxygenase, but with a loss of this modifying effect, arachidonic acid molecules are preferentially metabolized in the 5-lipoxygenase pathway, resulting in increased production of cysteinyl leukotrienes.

Question 29

Patients with AERD will react to ASA and NSAIDs that inhibit COX-1. So what can you use?

Answer 29

Selective COX-2 inhibitors almost never cause reactions in patients with AERD and can typically be taken safely.

Question 30

What happens if a pt has an anaphylactic reaction to an NSAID?

Answer 30

It’s usually drug specific and they can tolerate other NSAIDd

Question 31

Which HLA allele is strongly associated with hypersensitivity reactions for Abacavir (NRTI)?

Answer 31

HLA-B*5701

Question 32

What is the cause of anaphylaxis to Cetuximab?

Answer 32

IgE antibodies to cetuximab have been found in the majority of anaphylactic reactions and are specific for an oligosaccharide, galactose-α-1,3 galactose, which is present on the Fab portion of the cetuximab heavy chain.

Question 33

What fraction of the final treatment dose would be typical for a graded dose challenge?

Answer 33

1/100

Question 34

In cases of Systemic DILE which antibody levels are frequently positive?

Answer 34

Antihistone antibody

Question 35

In cases of cutaneous DILE which antibody levels are frequently positive?

Answer 35

AntiRo/SSA, antiLa/SSB or both

Question 36

Which MHC marker is associated with increased reactions to Insulin, Gold and Penicillamine?

Answer 36

HLA-DR3

Question 37

HLA-DR3-assoc with what conditions?

Answer 37

Grave’s and Hashimoto’s, type IA diabetes, Addison’s disease, Pernicious anemia, autoimmune hepatitis, and others.

Question 38

Stevens–Johnson syndrome to carbamazepine in Han-Chinese shows a strong association with which HLA?

Answer 38

strong association with HLA-B∗1502, but HLA-B∗1502 is not increased in Han-Chinese patients with milder, maculopapular drug eruptions. (Middleton)

Question 39

the N1 substituted ring appears to be important for IgE-mediated reactions. Because nonantibiotic sulfonamides lack these structural components, they would not be expected to cross-react with sulfonamide antibiotics. Several clinical studies demonstrated no increased risk of reactions to nonantibiotic sulfonamides in patients with a history of allergy to sulfonamide antibiotics

Answer 39

the N1 substituted ring appears to be important for IgE-mediated reactions. Because nonantibiotic sulfonamides lack these structural components, they would not be expected to cross-react with sulfonamide antibiotics. Several clinical studies demonstrated no increased risk of reactions to nonantibiotic sulfonamides in patients with a history of allergy to sulfonamide antibiotics