Chapter 7 - Pharmacology and Therapeutics Flashcards
What are some other rare adverse effects of IVIG
What are some pretreatment options for mild IVIG reactions
- thrombotic events, stroke, MI, hemolytic anemia, TRALI
- aspirin, tylenol, Benadryl, hydrocortisone, slow infusion rate
- for serious IVIG reactions, or history, have epi available
How does IgG Fc Receptor Blockade work
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
Silver Vial
1:10,000
What are three conditions for which IgG replacement should NOT be used
sIgA deficiency
IgG due to protein loss
IgG subclass deficiency
transient hypogam of infancy
In the IVIG manufacturing process, what does filtration do
filtration removes antibody aggregates and viruses
What changes in cytokine profile occur with AIT
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
what are contraindications to SLIT
severe asthma and eosinophilic esophagitis
What does IVIG contain
Mostly monomeric IgG (>95%) and small amounts of IgA and IgM
What forms of IgG replacement are available
generally IV, IM, SC. SCIG has fewer side effects and is an infusion at home. Benefits are stable trough levels and fewer side effects
in the IVIG manufacturing process, what does stabilization do
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
Review nomenclature for labelling AIT vials
In the IVIG manufacturing process, what does viral inactivation do
enveloped viruses can be inactivated by chemical methods (solvent/detergent, low pH)
physical methods are required for nonenveloped viruses (pasteurization, column chromatography, nanofiltration)
what is the effective maintenance dose for most inhalant allergens
between 5 and 20 micrograms per 0.5ml maintenance dose
What is the efficacy of AIT on asthma
Symptom scores improve and medication use decreases
decreases bronchial hyperreactivity but does NOT affect PFTs
particularly in children, AIT can help prevent allergic asthma
Green Vial
1:1000
What type of immune cells increase in AIT
CD4+CD25+ Treg cells (IL-10, TGF-beta)
CD8 cells
Why do some SCIG products come with hyaluronidase
ithis is because it is difficult to give large amounts of Ig by the subcutaneous route unless pretreated with hyaluronidase, which improves permeability
What are the FDA-approved indications for IVIG (8)
- 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
What stabilizer in IVIG is associated with acute renal failure
Sucrose
How is Ig isolated from plasma in the manufacturing process
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
What are some specific hyperimmune globulins that people prescribe to patients (7)
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
What are some key facts about aseptic meningitis with IVIG
history of migraine is a predisposing factor
associated with large doses, rapid infusions, and the treatment of patients with autoimmune/inflammatory disorders
What are the age considerations in AIT
There are no upper or lower age limits, but children should be able to communicate effectively and comorbidities in the elderly should be considered
Red Vial
1:1 (maintenance concentrate)
Review cross-reactivity patterns of allergen extracts
Review SLIT
5 grass SLIT - Oralair
Timothy Grass - Grastek
Ragweed - Ragwitek
dust mite - Odactra
local reactions common but pretty effective
what extracts are safe to mix with high-protease extracts
ragweed and cat (in 50% glycerin)
T/F Local reactions are common to AIT
redness or swelling dime to quarter size is common and do not predict systemics.
frequent large local reactions (>25 mm) may predict systemics
Approximately how many donors contribute to one dose of IVIG
15,000-60,000
What is the typical period of maintenance immunotherapy?
3-5 years
What is the serum half life of IVIG
3-4 weeks
Systemic reactions are rare - how rare?
what increases the risk?
0.2%, normally within 30 minutes
taking beta blockers increases risk
What is the standard starting dose of IVIG
400-600 mg/kg every 3-4 weeks
Review “Uses of Immunoglobulin Therapy”
Blue Vial
1:100
What are relative contraindications to AIT
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)
Which extracts degrade pollen
Mold and cockroach
What things decrease in AIT
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
Yellow Vial
1:10
monoclonal antibody against epidermal growth factor receptor
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
What is AIT an effective treatment for (4)
Allergic Rhinitis/Conjunctivitis
Allergic Asthma
Atopic Dermatitis with Aeroallergen Sensitization (dust mites)
Stinging-Insect Hypersensitivity
It is ok to mix dust mite (>=10% glycerin) with what extracts
pollen, dog, cat, cockroach, mold extracts
What vaccines have diminished immunogenicity after IVIG
Live virus vaccines don’t work as well when given shortly before or during several months after receipt of Ig products.
Besides Fc Receptor blockade and sialyated IgG fraction mediation, by what other mechanisms (3) does does IgG therapy have immunosuppresive effects
neutralization of autoantibodies, toxins, superantigens
inhibition of of cytokine production
inhibition of complement uptake/elimination of immune complexes
T/F Glycerin is associated with local reactions
F
however, it can be irritating and painful
What is the standard starting dose for SCIG
100mg/kg/week
How safe is IVIG
viral and prion elimination is considered to be safe
no transmission of any infectious diseases has occurred since the mid-1990s
list all the things that increase risk of systemics in AIT
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
What antibodies increase when AIT is started
IgG blocking antibody (initially IgG1 and IgG2 –> IgG4)
IgA
IgE (initially, in the first few months, but ultimately decreases over years)
How does the sialyated IgG fraction in IgG mediate immunosuppressive activity
terminal alpha-2-6 linked sialic acid residue on the N-linked glycans of the IgG Fc domain have been shown to be immunosuppressive
Which venoms can you mix together
venoms contain proteases and should not be mixed, except for vespid venoms (hornets/yellow jackets)
What are some mild reactions to IVIG administration
headache, fatigue, fever, chills, nausea, vomiting, myalgias
(flu-like symptoms)
usually rate-dependent, occur during initial doses, and improve over time
bonus question - What is the standard dose required for immunomodulation (as opposed to replacement)? IE, for patients with something like Kawasaki disease
in this case, higher doses are needed (2g/kg)
What’s the issue with IgA deficiency and IgG replacement
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
Why are patients with sIgA deficiency predisposed to anaphylaxis with IVIG and other blood products
sometimes they have antibodies to IgA.
one strategy is to use products with low IgA content, or pretreat with antihistamines and corticosteroids
what are major (1) and minor determinants (3) for penicillin
major benzylpenicilloyl polylysine (Pre-Pen)
minor penicillin G, penicilloate, penilloate (if available)
most PCN allergy (80%) is related to major determinant
what do you do if a patient has a reaction during desensitization?
what are contraindications?
repeat/decrease dose, treat, keep going
contraindications include TEN, DRESS, serum sickness, hepatitis, hemolytic anemia, nephritis. Basically anything type II-IV on Gell-Coombs
