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ACAAI Review for the Allergy/Immunology Boards > Chapter 7 - Pharmacology and Therapeutics > Flashcards

Chapter 7 - Pharmacology and Therapeutics Flashcards

1
Q

What are some other rare adverse effects of IVIG

What are some pretreatment options for mild IVIG reactions

A
  • thrombotic events, stroke, MI, hemolytic anemia, TRALI
  • aspirin, tylenol, Benadryl, hydrocortisone, slow infusion rate
  • for serious IVIG reactions, or history, have epi available
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2
Q

How does IgG Fc Receptor Blockade work

A

inhibits antibody-dependent cell-mediated cytoxocity (ADCC) by blockade of FcgammaRIII (CD16) (remember, this is the NK cell receptor)

inhibits antibody production by blocking FcgammaRIIb (CD32) on B lymphocytes

in ITP, IVIG generally blocks membrane Fc receptors on phagocytes in the spleen and liver

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3
Q

Silver Vial

A

1:10,000

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4
Q

What are three conditions for which IgG replacement should NOT be used

A

sIgA deficiency

IgG due to protein loss

IgG subclass deficiency

transient hypogam of infancy

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5
Q

In the IVIG manufacturing process, what does filtration do

A

filtration removes antibody aggregates and viruses

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6
Q

What changes in cytokine profile occur with AIT

A

shift from Th2 (IL-4, IL-5, IL-13) to Th1 (IFN-gamma, IL-12)

increase in Th1/Th2 ratio
increase in IFN-gamma/IL-4 ratio

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7
Q

what are contraindications to SLIT

A

severe asthma and eosinophilic esophagitis

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8
Q

What does IVIG contain

A

Mostly monomeric IgG (>95%) and small amounts of IgA and IgM

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9
Q

What forms of IgG replacement are available

A

generally IV, IM, SC. SCIG has fewer side effects and is an infusion at home. Benefits are stable trough levels and fewer side effects

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10
Q

in the IVIG manufacturing process, what does stabilization do

A

this helps prevent aggregation of Ig molecules

different chemicals are used (albumin, glycine, etc). low pH helps to get rid of aggregates but also minimize damage to the therapeutic activity of the Ig

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11
Q

Review nomenclature for labelling AIT vials

A
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12
Q

In the IVIG manufacturing process, what does viral inactivation do

A

enveloped viruses can be inactivated by chemical methods (solvent/detergent, low pH)

physical methods are required for nonenveloped viruses (pasteurization, column chromatography, nanofiltration)

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13
Q

what is the effective maintenance dose for most inhalant allergens

A

between 5 and 20 micrograms per 0.5ml maintenance dose

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14
Q

What is the efficacy of AIT on asthma

A

Symptom scores improve and medication use decreases

decreases bronchial hyperreactivity but does NOT affect PFTs

particularly in children, AIT can help prevent allergic asthma

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15
Q

Green Vial

A

1:1000

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16
Q

What type of immune cells increase in AIT

A

CD4+CD25+ Treg cells (IL-10, TGF-beta)

CD8 cells

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17
Q

Why do some SCIG products come with hyaluronidase

A

ithis is because it is difficult to give large amounts of Ig by the subcutaneous route unless pretreated with hyaluronidase, which improves permeability

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18
Q

What are the FDA-approved indications for IVIG (8)

A
  1. primary immunodeficiencies 2. CLL 3. Kawasaki disease 4. following stem cell transplant with B-lymphocyte non-engraftment 5. pediatric HIV infection (recurrent bacterial infections) 6. ITP 7. CIDP 8. bone marrow transplant
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19
Q

What stabilizer in IVIG is associated with acute renal failure

A

Sucrose

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20
Q

How is Ig isolated from plasma in the manufacturing process

A

Broadly speaking, ethanol is used to fractionate the pooled plasma.

Usually, the modified Cohn-Oncley cold ethanol fractionation method is used. This step also gets rid of prion particles

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21
Q

What are some specific hyperimmune globulins that people prescribe to patients (7)

A

globulins from people who have high titers to a desired antibody, either naturally acquired or stimulated by immunization. They are used to transfer passive immunity for postexposure prophylaxis

examples are to hepatitis B, rabies, tetanus, varicella-zoster, vaccinia, CMV, and RSV

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22
Q

What are some key facts about aseptic meningitis with IVIG

A

history of migraine is a predisposing factor

associated with large doses, rapid infusions, and the treatment of patients with autoimmune/inflammatory disorders

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23
Q

What are the age considerations in AIT

A

There are no upper or lower age limits, but children should be able to communicate effectively and comorbidities in the elderly should be considered

24
Q

Red Vial

A

1:1 (maintenance concentrate)

25
Q

Review cross-reactivity patterns of allergen extracts

A
26
Q

Review SLIT

A

5 grass SLIT - Oralair

Timothy Grass - Grastek

Ragweed - Ragwitek

dust mite - Odactra

local reactions common but pretty effective

27
Q

what extracts are safe to mix with high-protease extracts

A

ragweed and cat (in 50% glycerin)

28
Q

T/F Local reactions are common to AIT

A

redness or swelling dime to quarter size is common and do not predict systemics.

frequent large local reactions (>25 mm) may predict systemics

29
Q

Approximately how many donors contribute to one dose of IVIG

A

15,000-60,000

30
Q

What is the typical period of maintenance immunotherapy?

A

3-5 years

31
Q

What is the serum half life of IVIG

A

3-4 weeks

32
Q

Systemic reactions are rare - how rare?

what increases the risk?

A

0.2%, normally within 30 minutes

taking beta blockers increases risk

33
Q

What is the standard starting dose of IVIG

A

400-600 mg/kg every 3-4 weeks

34
Q

Review “Uses of Immunoglobulin Therapy”

A
35
Q

Blue Vial

A

1:100

36
Q

What are relative contraindications to AIT

A

pregnancy (ok for maintenance, not buildup)

serious immunodeficiency

malignancy

poorly controlled or severe asthma

significant CV disease

caution with beta blockers (AIT) and ACEI (VIT)

37
Q

Which extracts degrade pollen

A

Mold and cockroach

38
Q

What things decrease in AIT

A

seasonal rise in allergen-specific IgE

low affinity IgE receptor (FcERII/CD23)

basophil hyperreactivity

recruitment of basophils, eos, and mast cells in nose/lung

allergen-specific lymphocyte proliferation

39
Q

Yellow Vial

A

1:10

40
Q

monoclonal antibody against epidermal growth factor receptor

A

Cetuximab - used in the treatment of some colorectal and head/neck cancers.

has a novel mechanism of anaphylaxis that can be predicted by the presence of IgE antibodies against naturally occuring galactose-alpha-1,3-galactose (oligosaccharides related to the ABO blood group) even before exposure to the drug.

these pre-existing IgE antibodies appear to put patients at risk for anaphylaxis to this drug

41
Q

What is AIT an effective treatment for (4)

A

Allergic Rhinitis/Conjunctivitis

Allergic Asthma

Atopic Dermatitis with Aeroallergen Sensitization (dust mites)

Stinging-Insect Hypersensitivity

42
Q

It is ok to mix dust mite (>=10% glycerin) with what extracts

A

pollen, dog, cat, cockroach, mold extracts

43
Q

What vaccines have diminished immunogenicity after IVIG

A

Live virus vaccines don’t work as well when given shortly before or during several months after receipt of Ig products.

44
Q

Besides Fc Receptor blockade and sialyated IgG fraction mediation, by what other mechanisms (3) does does IgG therapy have immunosuppresive effects

A

neutralization of autoantibodies, toxins, superantigens

inhibition of of cytokine production

inhibition of complement uptake/elimination of immune complexes

45
Q

T/F Glycerin is associated with local reactions

A

F

however, it can be irritating and painful

46
Q

What is the standard starting dose for SCIG

A

100mg/kg/week

47
Q

How safe is IVIG

A

viral and prion elimination is considered to be safe

no transmission of any infectious diseases has occurred since the mid-1990s

48
Q

list all the things that increase risk of systemics in AIT

A

beta blockers

unstable asthma

history of previous systemics

during “priming” of pollen season

during buildup

during accelerated or rushed protocols

first injection from new vial

dosing error

49
Q

What antibodies increase when AIT is started

A

IgG blocking antibody (initially IgG1 and IgG2 –> IgG4)

IgA

IgE (initially, in the first few months, but ultimately decreases over years)

50
Q

How does the sialyated IgG fraction in IgG mediate immunosuppressive activity

A

terminal alpha-2-6 linked sialic acid residue on the N-linked glycans of the IgG Fc domain have been shown to be immunosuppressive

51
Q

Which venoms can you mix together

A

venoms contain proteases and should not be mixed, except for vespid venoms (hornets/yellow jackets)

52
Q

What are some mild reactions to IVIG administration

A

headache, fatigue, fever, chills, nausea, vomiting, myalgias

(flu-like symptoms)

usually rate-dependent, occur during initial doses, and improve over time

53
Q

bonus question - What is the standard dose required for immunomodulation (as opposed to replacement)? IE, for patients with something like Kawasaki disease

A

in this case, higher doses are needed (2g/kg)

54
Q

What’s the issue with IgA deficiency and IgG replacement

A

some people with IgA deficiency have anti-IgA antibodies, thus can have problems when they receive this blood product. There are products containing low IgA

55
Q

Why are patients with sIgA deficiency predisposed to anaphylaxis with IVIG and other blood products

A

sometimes they have antibodies to IgA.

one strategy is to use products with low IgA content, or pretreat with antihistamines and corticosteroids

56
Q

what are major (1) and minor determinants (3) for penicillin

A

major benzylpenicilloyl polylysine (Pre-Pen)

minor penicillin G, penicilloate, penilloate (if available)

most PCN allergy (80%) is related to major determinant

57
Q

what do you do if a patient has a reaction during desensitization?

what are contraindications?

A

repeat/decrease dose, treat, keep going

contraindications include TEN, DRESS, serum sickness, hepatitis, hemolytic anemia, nephritis. Basically anything type II-IV on Gell-Coombs

ACAAI Review for the Allergy/Immunology Boards (11 decks)

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