Exam 1: Immunology, Hypersensitivity, SOT, Immunosuppression Flashcards
What is Polyclonal ABs?
ABs harvested from 1000 patients (animal or human) with various B cells. Increased risk of hypersensitivity reaction due to lack of purity/specificity.
Artificial Passive immunity.
What is an example of a Type I hypersensitivity?
Anaphylaxis
What immunoglobulin/cells mediate the anaphylactic reaction
IgE, B/plasma cells, macrophages
What is the IMMEDIATE treatment (Rx) for anaphylaxis?
Epinephrine 1:1000 IM/SQ every 15-20 mins until respiratory relief
Oxygen treatment
What is the LATE treatment (Rx) for anaphylaxis?
25-50 mg diphenhydramine (parenteral)
Anti-H2 receptor blocker (ie. Cimetidine, famotidine)
Hypotension = IV fluids
IV hydrocortisone to reduce recurrence risk
Penicillin Type 1 hypersensitivities are fairly common. What other class of drug should we be careful using? What overlapping element causes the cross reactivity?
Cephalosporines
The side chain moieties of the beta lactam cause reactivity
What is an example of complement-mediated lysis (type 2 hypersensitivity)?
ABO mismatched blood transfusion
What is an example of macrophage-mediated phagocytosis (type 2 hypersensitivity)? What immunoglobulin is this mediated by?
Erythroblastosis fetalis
From the IgG opsonization
When a mother is administered Rho-Gam, what is the Rh0D Ig actually doing?
Binds to the Rh0 positive RBCs of the fetus and protects them from the mother’s anti-Rh0 antibodies.
What is an example of and exogenous Ag-caused type 3 hypersensitivity? An endogenous Ag-caused T3 hypersensitivity?
Exogenous = Gluten allergy, Serum Sickness*
Endogenous = Drug-induced Lupus
What agents may cause serum sickness? (10)
Animal serums
Bee venom
Cefaclor
Insulin
Iron dextran
IV Ig
mAb
Penicillins
Sulfonamides
What drugs may cause Drug-Induced Lupus?
Hydralazine
Procainamide
Isoniazid
Quinidine
TNF-a inhibitors
What treatments (Rx) should be used for contact dermatitis?
Topical steroids (hydrocortisone)
Antihistamines
Topical immunomodulators (ie. TAC)
Systemic steroids (last line; many AEs)
How do we test for anergy when conducting a TST/Tuberculin PPD?
Do a control skin test (candida/mumps) - if either are positive, then no anergy
What are the cutoffs between TEN, SJS/TEN and SJS?
SJS = affects <10% body surface area
SJS/TEN = affects 15-30% body surface area
TEN = affects >30% body surface area
What drugs may cause SJS/TEN?
Sulfa drugs
Some antibiotics (ampicillin/amoxicillin, fluoroquinolones, cephalosporins)
Anti-epileptics
Etc: allopurinol, piroxicam
What subtype is SJS/TEN?
Type IV-C hypersensitivity
What non-Rxs may trigger SJS/TEN?
Infections
Viruses
Vaccines
Graft v Host disease
What is AGEP?
Type IV-D hypersensitivity
Rapid appearance of small pustules and erythema followed by desquamation of skin
Unclear physiology, 90% caused by drugs
What drugs cause “allergy-like” reactions?
Beta Lactams
Sulfonamides
Anticonvulsants
Additives (dyes, parabens)
Biological
Chemo agents
Aspirin/NSAIDS**
Name the 3 lymphocyte proliferation inhibitors
Mycophenolate Mofetil (MMF)
Mycophenalic Acid (MPS)
Azathioprine [older]
What are the 3 stages of immunosuppressive therapy?
- Induction
- Maintenance
- Rejection
Explain the pre-transplant Rx therapy regimen
One induction agent (depleting/non-depleting)
IV bolus methylprednisolone
Mycophenolic Acid dose (MMF/MPS)
Explain the post op INDUCTION (days 0-7) Rx therapy regimen
- A few doses induction agent (depleting/non-depleting) then D/C
- IV methylprednisolone —> convert to ORAL prednisone taper
- Mycophenolic Acid dosing
- Initiate low dose CNI
Explain the maintenance therapy regimen (SOT)
- Mycophenolic acid dosing
- CNI dose continuously titrated by TDM
- Prednisone taper cont.
Monitor allograft function + AEs
What CNI+Steroid Taper is MOST COMMONLY used?
Tacrolimus + MMF/EC-MPS + Prednisone
(Can either use mycophenolate mofetil OR enteric coated Mycophenolic Sodium)
What 6 conditions cause secondary (acquired) immunodeficiency?
Spleen removal
HIV
Immunosuppressive for graft rejection**
Protein-calorie malnutrition
Radiation/chemotherapy
Bone marrow dysfunctional from cancers
“SHIP R&B”
What are the IMMEDIATE release Tacrolimus drugs? Can we substitute them out?
Prograf**
+ generics
NOT substitutable
What are the EXTENDED release Tacrolimus drugs? Can we substitute them out?
Astagraf XL**
Envarsus**
IV Prograf = continuous infusion
Not interchangeable/subtitutable
What are the Cyclosporine drugs? Which two can we substitute with each other?
Neoral* [BID]
Gengraf* [BID]
Sandimmune (po) [QD]
Sandimmune IV [may cause anaphylaxis, last resort]
- = modified CYA, MAY SUBSTITUTE
What are the adverse effects of cyclosporine? (4 maj, 4 min)
Hyperlipidemia**
Nephrotoxicity**
Tremor, headache**
HTN**
Hyperglycemia
Gingival hyperplasia
Hirsutism
Diarrhea, vomiting
What are the adverse effects of tacrolimus? (4 maj, 3 min)
Diarrhea, nausea**
Nephrotoxicity**
Tremor, headache**
Insomnia**
Hyperglycemia
Hyperlipidemia
HTN
(All minor ones start w “hyper”)
CNIs are metabolized by CYP3A4s. What are some CYP3A4 INHIBITORS?
CCBs
Antifungals (-zole)
Antibiotics [clarithromycin, erythromycin]
Protease Inhibitors (-vir)
Gastric acid suppressors (PPIs, H2RAs, etc)
Grapefruit juice (naringin)
CNIs are metabolized by CYP3A4s. What are some CYP3A4 INDUCERS?
Antibiotics [rifampin, rifabutin]
Antifungal [caspofungin]
Anticonvulsants [phenytoin, phenobarbital, carbamazepine, oxcarbazepine]
Herbals [St. John’s Wort]
Others = octreotide, orlistat
Finish the phrases on CNI PK:
CYA and TAC exhibit _______ kinetics
______ concentration monitoring is state of practice
Linear kinetics
Trough
Mycophenolate Mofetil is _____ release
Mycophenolic Acid Sodium is ______ release
Which is a prodrug? Can they be interchanged?
MMF = regular release, PRODRUG
MPS = delayed release
Not interchangeable
What is the MOA for MPAs?
Mycophenolic acids inhibit enzyme IMPDH which interferes with the purine metabolism required for T lymphocyte proliferation.
While not interchangable, what is the RATIO between MMF and EC-MPS? **
1000mg MMF : 720 mg EC-MPS
How do some drugs have enterohepatic recirculation with MPAs? (4 drugs)
Cyclosporine = INHIBITS MRP2, reduces MPA AUC (MPA less effective)
Tacrolimus = minimal inhibition of MRP, lower daily dose needed for equal MPA effect (EHC)
Cholestyramine/Bile Acid Reducers = reduced MPA AUC
Antibiotics = reduced MPA AUC
What drugs are renally cleared and thus interact with MPA?
Acyclovir
Ganciclovir
Co-trimoxazole
How do COCs and MPA interact?
MPA decreases levonorgestrel AUC significantly
MPA may alter the albumin binding of which 2 drugs?
Phenytoin
Aspirin
Which drug class may increase MPA metabolism?
Glucocorticoids
Name the adverse effects of mycophenolic acids?
GI: N/V, diarrhea, dyspepsia
Hematologic: leukopenia, neutropenia, anemia, thrombocytopenia
Opportunistic infections
CNS: dizziness, insomnia, headache
Cardiovascular
What effect does glucocorticoid therapy have on the HPA axis?
As cortisol concentrations increase, it functions as a negative feedback on hypothalamic and pituitary hormones.
What is the interchange ratio between prednisone and methylprednisolone?
5:4 (Prednisone:Methylprednisolone)
What are some metabolic inhibitors of glucocorticoids? (6)
Macrolide antibiotics (erythromycin, clarithromycin)
Oral contraceptives
Conjugated estrogens
Ketoconazole
Naproxen
Isoniazid
Cyclosporine*
What are some metabolic inducers of glucocorticoids? (5)
Phenytoin
Phenobarbital
Rifampin
Carbamazepine
Ephedrine
What are some drugs that are metabolically inhibited BY glucocorticoids? (3)
Tacrolimus
Cyclosporine
MPA
What two classes of drugs that decrease steroid absorption?
Cholestyramine
Antacids
What are some long term adverse effects of glucocorticoids? (Many!)
Adrenal Gland: Adrenal Atrophy, **Cushing’s Syndrome
Cardiovascular System: Dyslipidemia, HTN, Thrombosis, Vasculitis
Central Nervous System: Changes in behavior, cognition, memory, and mood
Gastrointestinal System: GI Bleeding, Pancreatitis, Peptic Ulcer
Immune System: Broad Immunosuppression, Activation of Latent Viruses
Integument: delayed wound healing, striae, echimoses/easy bruising
Skeletal: Bone thinning, osteoporosis
Eyes: cataracts, glaucoma
What are 6 post-transplant complications?
HTN
Opportunistic infections
Diabetes
Hyperlipidemia
Osteoporosis
Lymphoproliferative disorder
What are the four goals of immunosuppressive Rx treatment?
- Suppress immune response
- Use a multiple drug regimen approach
- Use different MoA drugs
- Minimize long term drug related AEs
What are the two depleting induction agents?
Anti-thymocyte globulin
Alemtuzumab
How should anti-thymocyte globulin be administered?
IV infusion over 4-6 hours for 2-4 daily doses
What are the two types of anti-thymocye globulin and what are the source animals?
ATGAM = horse Ab
Thymoglobulin = rabbit Ab
What is an adverse effect from anti-thymocyte globulin treatment?
Flu-like symptoms (CYTOKINE RELEASE SYNDROME)
Patients to receive anti-thymocyte globulin should be pre-medicated with…?
Diphenhydramine
APAP
High risk patients should receive _________ induction therapy and low risk patients should receive ________ induction therapy post op.
High risk = depleting
Low risk = non-depleting
What is the MoA for anti-thymocyte globulins?
Ab coat host T cells and destroy them
Alemtuzumab is not FDA approved as a depleting inducing agent. What is it actually approved for?
Multiple sclerosis
What cluster differentiation (CD) is targeted by Alemtuzumab Abs?
CD52
What are the two dosing regimen options for Alemtuzumab?
- TWO doses x 0.3 mg/kg/dose
- 20-30 mg IV single dose over 2-3 hours
What are some adverse effects of Alemtuzumab? (3)
Infusion-related reactions (HAMA)
GI disorders
Profound lymphopenia/neutropenia/thrombocytopenia
What NON-DEPLETING induction agent drugs are there? What is it’s class + MoA?
IL-2 receptor blockers
Basiliximab = mAb binds to CD25 which prevents activation of T cell proliferation
[no depletion, only stopping proliferation]
Daclizumab (off-market)
If a patient taking a CNI is above the target range (ie. CYA trough is 350 ng/mL when goal is 150<x<250) what should you do?
- Hold one dose
- Reduce the dosing regimen by 25-30%
- Repeat trough in ~24 hrs
What is a Granulocyte-Monocyte CSF (GM-CSF)? What is one example of an Rx?
Causes a dose-dependent increase in the production of neutrophils and monocytes
Sargramostism
What is a Granulocyte CSF (G-CSF)? What is one example of an Rx?
Increases neutrophil counts only
Filgrastim (Neupogen)
Pegfilgrastim (Neulasta)
How do erythropoesis-stimulating agents (ESAs) like Epoetin-Alfa work?
Stimulates erythropoietin formation, which responds to low oxygen levels by increasing RBC production in bone marrow, thereby increasing the oxygen carrying capacity.
Interferons are antiviral and growth inhibitors of malignant cells. What is Peginterferon Alfa-2a/b indicated for and why are pegylated interferons better?
Indicated for Hep C virus (HCV)
Pegylation improves PK and reduces dosing frequency. Also reduces adverse effects & increased sustained viral response.
Is Alemtuzumab monoclonal or polyclonal?
Monoclonal!
