Exam 1: Immunology, Hypersensitivity, SOT, Immunosuppression Flashcards

1
Q

What is Polyclonal ABs?

A

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.

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2
Q

What is an example of a Type I hypersensitivity?

A

Anaphylaxis

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3
Q

What immunoglobulin/cells mediate the anaphylactic reaction

A

IgE, B/plasma cells, macrophages

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4
Q

What is the IMMEDIATE treatment (Rx) for anaphylaxis?

A

Epinephrine 1:1000 IM/SQ every 15-20 mins until respiratory relief
Oxygen treatment

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5
Q

What is the LATE treatment (Rx) for anaphylaxis?

A

25-50 mg diphenhydramine (parenteral)
Anti-H2 receptor blocker (ie. Cimetidine, famotidine)
Hypotension = IV fluids
IV hydrocortisone to reduce recurrence risk

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6
Q

Penicillin Type 1 hypersensitivities are fairly common. What other class of drug should we be careful using? What overlapping element causes the cross reactivity?

A

Cephalosporines
The side chain moieties of the beta lactam cause reactivity

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7
Q

What is an example of complement-mediated lysis (type 2 hypersensitivity)?

A

ABO mismatched blood transfusion

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8
Q

What is an example of macrophage-mediated phagocytosis (type 2 hypersensitivity)? What immunoglobulin is this mediated by?

A

Erythroblastosis fetalis
From the IgG opsonization

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9
Q

When a mother is administered Rho-Gam, what is the Rh0D Ig actually doing?

A

Binds to the Rh0 positive RBCs of the fetus and protects them from the mother’s anti-Rh0 antibodies.

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10
Q

What is an example of and exogenous Ag-caused type 3 hypersensitivity? An endogenous Ag-caused T3 hypersensitivity?

A

Exogenous = Gluten allergy, Serum Sickness*
Endogenous = Drug-induced Lupus

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11
Q

What agents may cause serum sickness? (10)

A

Animal serums
Bee venom
Cefaclor
Insulin
Iron dextran
IV Ig
mAb
Penicillins
Sulfonamides

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12
Q

What drugs may cause Drug-Induced Lupus?

A

Hydralazine
Procainamide
Isoniazid
Quinidine
TNF-a inhibitors

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13
Q

What treatments (Rx) should be used for contact dermatitis?

A

Topical steroids (hydrocortisone)
Antihistamines
Topical immunomodulators (ie. TAC)
Systemic steroids (last line; many AEs)

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14
Q

How do we test for anergy when conducting a TST/Tuberculin PPD?

A

Do a control skin test (candida/mumps) - if either are positive, then no anergy

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15
Q

What are the cutoffs between TEN, SJS/TEN and SJS?

A

SJS = affects <10% body surface area
SJS/TEN = affects 15-30% body surface area
TEN = affects >30% body surface area

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16
Q

What drugs may cause SJS/TEN?

A

Sulfa drugs
Some antibiotics (ampicillin/amoxicillin, fluoroquinolones, cephalosporins)
Anti-epileptics
Etc: allopurinol, piroxicam

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17
Q

What subtype is SJS/TEN?

A

Type IV-C hypersensitivity

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18
Q

What non-Rxs may trigger SJS/TEN?

A

Infections
Viruses
Vaccines
Graft v Host disease

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19
Q

What is AGEP?

A

Type IV-D hypersensitivity
Rapid appearance of small pustules and erythema followed by desquamation of skin
Unclear physiology, 90% caused by drugs

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20
Q

What drugs cause “allergy-like” reactions?

A

Beta Lactams
Sulfonamides
Anticonvulsants
Additives (dyes, parabens)
Biological
Chemo agents
Aspirin/NSAIDS**

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21
Q

Name the 3 lymphocyte proliferation inhibitors

A

Mycophenolate Mofetil (MMF)
Mycophenalic Acid (MPS)
Azathioprine [older]

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22
Q

What are the 3 stages of immunosuppressive therapy?

A
  1. Induction
  2. Maintenance
  3. Rejection
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23
Q

Explain the pre-transplant Rx therapy regimen

A

One induction agent (depleting/non-depleting)
IV bolus methylprednisolone
Mycophenolic Acid dose (MMF/MPS)

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24
Q

Explain the post op INDUCTION (days 0-7) Rx therapy regimen

A
  • 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
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25
Explain the maintenance therapy regimen (SOT)
- Mycophenolic acid dosing - CNI dose continuously titrated by TDM - Prednisone taper cont. Monitor allograft function + AEs
26
What CNI+Steroid Taper is MOST COMMONLY used?
Tacrolimus + MMF/EC-MPS + Prednisone (Can either use mycophenolate mofetil OR enteric coated Mycophenolic Sodium)
27
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”
28
What are the IMMEDIATE release Tacrolimus drugs? Can we substitute them out?
Prograf** + generics NOT substitutable
29
What are the EXTENDED release Tacrolimus drugs? Can we substitute them out?
Astagraf XL** Envarsus** IV Prograf = continuous infusion Not interchangeable/subtitutable
30
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
31
What are the adverse effects of cyclosporine? (4 maj, 4 min)
Hyperlipidemia** Nephrotoxicity** Tremor, headache** HTN** Hyperglycemia Gingival hyperplasia Hirsutism Diarrhea, vomiting
32
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”)
33
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)
34
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
35
Finish the phrases on CNI PK: CYA and TAC exhibit _______ kinetics ______ concentration monitoring is state of practice
Linear kinetics Trough
36
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
37
What is the MOA for MPAs?
Mycophenolic acids inhibit enzyme IMPDH which interferes with the purine metabolism required for T lymphocyte proliferation.
38
While not interchangable, what is the RATIO between MMF and EC-MPS? **
1000mg MMF : 720 mg EC-MPS
39
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
40
What drugs are renally cleared and thus interact with MPA?
Acyclovir Ganciclovir Co-trimoxazole
41
How do COCs and MPA interact?
MPA decreases levonorgestrel AUC significantly
42
MPA may alter the albumin binding of which 2 drugs?
Phenytoin Aspirin
43
Which drug class may increase MPA metabolism?
Glucocorticoids
44
Name the adverse effects of mycophenolic acids?
GI: N/V, diarrhea, dyspepsia Hematologic: leukopenia, neutropenia, anemia, thrombocytopenia Opportunistic infections CNS: dizziness, insomnia, headache Cardiovascular
45
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.
46
What is the interchange ratio between prednisone and methylprednisolone?
5:4 (Prednisone:Methylprednisolone)
47
What are some metabolic inhibitors of glucocorticoids? (6)
Macrolide antibiotics (erythromycin, clarithromycin) Oral contraceptives Conjugated estrogens Ketoconazole Naproxen Isoniazid Cyclosporine*
48
What are some metabolic inducers of glucocorticoids? (5)
Phenytoin Phenobarbital Rifampin Carbamazepine Ephedrine
49
What are some drugs that are metabolically inhibited BY glucocorticoids? (3)
Tacrolimus Cyclosporine MPA
50
What two classes of drugs that decrease steroid absorption?
Cholestyramine Antacids
51
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
52
What are 6 post-transplant complications?
HTN Opportunistic infections Diabetes Hyperlipidemia Osteoporosis Lymphoproliferative disorder
53
What are the four goals of immunosuppressive Rx treatment?
1. Suppress immune response 2. Use a multiple drug regimen approach 3. Use different MoA drugs 4. Minimize long term drug related AEs
54
What are the two depleting induction agents?
Anti-thymocyte globulin Alemtuzumab
55
How should anti-thymocyte globulin be administered?
IV infusion over 4-6 hours for 2-4 daily doses
56
What are the two types of anti-thymocye globulin and what are the source animals?
ATGAM = horse Ab Thymoglobulin = rabbit Ab
57
What is an adverse effect from anti-thymocyte globulin treatment?
Flu-like symptoms (CYTOKINE RELEASE SYNDROME)
58
Patients to receive anti-thymocyte globulin should be pre-medicated with…?
Diphenhydramine APAP
59
High risk patients should receive _________ induction therapy and low risk patients should receive ________ induction therapy post op.
High risk = depleting Low risk = non-depleting
60
What is the MoA for anti-thymocyte globulins?
Ab coat host T cells and destroy them
61
Alemtuzumab is not FDA approved as a depleting inducing agent. What is it actually approved for?
Multiple sclerosis
62
What cluster differentiation (CD) is targeted by Alemtuzumab Abs?
CD52
63
What are the two dosing regimen options for Alemtuzumab?
1. TWO doses x 0.3 mg/kg/dose 2. 20-30 mg IV single dose over 2-3 hours
64
What are some adverse effects of Alemtuzumab? (3)
Infusion-related reactions (HAMA) GI disorders Profound lymphopenia/neutropenia/thrombocytopenia
65
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)
66
If a patient taking a CNI is above the target range (ie. CYA trough is 350 ng/mL when goal is 150
1. Hold one dose 2. Reduce the dosing regimen by 25-30% 3. Repeat trough in ~24 hrs
67
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
68
What is a Granulocyte CSF (G-CSF)? What is one example of an Rx?
Increases neutrophil counts only Filgrastim (Neupogen) Pegfilgrastim (Neulasta)
69
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.
70
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.
71
Is Alemtuzumab monoclonal or polyclonal?
Monoclonal!