Pbt: Immunosuppressants

Front 1

Why use multidrug and intensive induction approach for immunosuppressive therapy?

Back 1

1. maximizes therapeutic effect since different drug act on different mechanisms.
2. synergistic effect allow for lower dosage and lower toxcity.

Front 2

What are the 7 mechanistic approaches of immunosuppressants?

Back 2

1. inhibition of gene expression: glucocorticoids
2. antiproliferative and cytotoxic agents: antimetabolite, alkylating agents
3. inhibition of lympgocyte activation: calcineurin inhibitors, mTOR inhibitors.
4. neutralization of cytokines: TNF-α inhibitors, IL-1, IL-6 inhibitors.
5. antibodies to immune cells: polyclonal and monoclonal antibodies.
6. inhibition of costimulation.
7. inhibition of lymocyte adhesion and hoiming: Efalizumab, FTY720.
8. inhibition of complement activation: eculizumab.

Front 3

Which two of the following glucocorticoids are bound to cortisol-binding globulin and albumin?
A. Cortisol
B. Prednisolone
C. Methylprednisolone
D. Dexamethasone

Back 3

A, B

Front 4

Which is the drug to use for 1st dose cytokine release syndrome in transplant patients treated with anti-CD3 and to a lesser extent thymoglobulin?

Back 4

Glucocorticoids.

Front 5

How do glucocorticoids produce anti-inflammatory effect?

Back 5

bind to GRE in the promotor region and stimulate expression of lipocortine to block PLA2, therefore production pro-inflammatory molecules is reduced.

Front 6

Glucocorticoids have profound adverse effects such as growth retardation, osteronecrosis, osteoprosis, poor wound healing and so on. How do you minimize these side effects?

Back 6

1. taper as soon and as rapidly as possible.
2. alternative-day dosing
3. use additional immunosuppressants or replace with nonsteroidal immunosuppressants.
4. Ca2+ and Vit D supplements and hormone replacement.

Front 7

Why do you need to slowly taper glucocorticoid dosage during termination of transplant therapy?

Back 7

Abrupt cessation can result in acute adrenal insufficiency because the hypothalamus and pituitary gland require time to re-establish adequate ACTH production.

Front 8

Which class of drug is AZA?
What is its mechanism of action?
Which enzyme is required to turn it into the active drug mercaptopurine?

Back 8

1. Antimetabolite
2. Anti-proliferative and cytotoxic: depletes purine pool by inhibiting conversion of IMP to AMP and GMP.
3. glutathione

Front 9

Which drugs does AZA interact with?

Back 9

1. allopurinal: inhibits xanthine oxidase which is needed in AZA degradation.
2. Other myelosuppressive agents or ACE inhibitors: will cause leukopenia, thrombocytopenia, and anemia.

Front 10

Which drug can not be used in conjunction with allopurinol or ACE inhibitors?

Back 10

AZA
1. allopurinol: increases T1/2.
2. ACE inhibitors: leukopenia, thrombocytopenia, anemia.

Front 11

Which drug has toxicity of sepsis associated with CMV or viral infection when used with tacrlimus?

Back 11

Mycophenolate mofetil

Front 12

Which drug can not be used with mycophenolate mefetil?

Back 12

1. Tacrolimus: impair converison of MPA to phenolic glucuronide.
2. antacids containing Al or Mg: decrease absorption.
3. cholestyramine: disrupt enterohepatic reabsorption by binding to bile acids.
4. acyclovir/gancyclovir: compete with pheolic glucuronide for tubular secretion.

Front 13

Which drug interacts with acyclovir?

Back 13

Mycophenolate mofetil

Front 14

Which drug interacts with antacids containing Al or Mg hydroxide?

Back 14

Mycophenolate mofetil: decrease absorption.

Front 15

Which antimetabolite interfere with purine sythesis?
A. AZA
B. Mycophenolate mofetil
C. Leflunomide
D. Methotrexate

Back 15

A, B

Front 16

Which antimetabolite interfere with pyrimidine sythesis?
A. AZA
B. Mycophenolate mofetil
C. Leflunomide
D. Methotrexate

Back 16

C

Front 17

Which is the most effective drug in reducing B cell populations?
A. AZA
B. Mycophenolate mofetil
C. Leflunomide
D. Methotrexate

Back 17

C

Front 18

Which two drugs interact with cholestyramine?

Back 18

Mycophenolate mofetil
Leflunomide

Front 19

What is the mechanism of action of methotrexate?

Back 19

Inhibit folate synthesis and induces apoptosis of CD4 and CD8 T cells.

May be related to increased adenosine level.

Front 20

What does a high level of adenosine cause?

Which drug might increase adenosine level?

Back 20

1. A potent anti-inflammatory agent: inhibit neutrophil superoxide generation, adhesion, and inhibits phagocytosis of IgG coated particles.

2. methotrexate

Front 21

Which antimetabolite drug can be used for cancer treatment?

Back 21

Methotrexate

Front 22

Which drug may cause pneumonitis characterized by patchy inflammatory infiltrates?

Back 22

Methotrexate

Front 23

Which drug is excreted unchanged in urine?

Back 23

Methotrexate

Front 24

Which population of people has higher sensitivity to methotrexate?

Back 24

People with genetic polymorphism C677T

Front 25

What are some drug interations with methotrexate?

Back 25

1. drugs that compete to bind serum albumin
2. drugs that compete for tubular secretion
3. NAIDS: reduces renal blood flow.
4. Cisplatin: nephrotoxic.
5. Aspirin/Piperacillin: weak organic acids.

Front 26

Which drug interacts with NSAIDs and aspirin?

Back 26

Methotrexate

Front 27

Which drug interacts with cisplatin?

Back 27

Methotrexate: nephrotoxic

Front 28

Which drug is a derivative of nidrogen mustard?

Back 28

cyclophosphamide

Front 29

Which alkylation is the major mechanism of cytotoxicity in cyclophosphamide?

Back 29

bis-alkylation

Front 30

Which drug may cause childhood nephritic syndrome?

Back 30

cyclophosphamide

Front 31

Which is the drug that should avoid taking at night and can be detoxified by mesna?

Back 31

cyclophosphamide

Front 32

Which drug causes water intoxification at high dose?

Back 32

cyclophosphamide: cause inappropriate secretion of vasopressin.

Front 33

Which drug does leflunomide interact with?

Back 33

Cholestyramine: quick removal and wash out of leflunomide becaused of interrupted enterohepatic circulation by cholestyramine binding with bile acids.

Front 34

Name one transplant therapy drug whose initial dose is not given before transplantation. Why?

Back 34

Cyclosporin A: concern of nephrotoxicity especially for renal transplant.

Front 35

What is a major toxicity associated with cyclosporin A?

Back 35

nephrotoxicity and renal dysfunction.

Front 36

Which drug may cause tremor, hirsutism, gum hyperplasia?

Back 36

cyclosporin A

Front 37

Which drug can be used to treat uveitis and Behcet's acute ocular syndrome?

Back 37

cyclosporin A

Front 38

Name a drug that is a specific inhibitior of T cell-mediated immunity.

Back 38

Cyclosporin A: block IL-2 expression, also increases TGF-β which inhibits IL-2 stimulated T cell proliferation.

Tacrolimus: similar mechanism.

Front 39

One of the toxicity of cyclosporin A is interstitial fibrosis. Explain.

Back 39

Cyclosporin A increases expression of TGF-β that cause cells to produce ECM.

Front 40

Are SANIMMUNE and NEORAL formulation of cyclosporin A bioeauivalent? Which one is more uniform and has higher bioavailability?

Back 40

1. No.
2. NEORAL formulation

Front 41

Where is cyclosporin metabolized?

Back 41

Liver: CYP3A. Dosage should be adjusted with hepatic dysfunction.

Front 42

What are some drugs that can't be used with NSAIDS?

Back 42

methotrexate
cyclosporin A

*cyclosporin A elevateds methotrexate levels.

Front 43

What are some drug interactions with cyclodporin A?

Back 43

1. P450 enzymes
2. sirolimus: aggrevates cyclosporinA induced renal dysfunction. The other way arround: hyperlipidemia, myelosuppression.
3. NSAIDS: renal dysfunction
4. elevated methotrexate
5. reduced clearance of prednisolone, digoxin statins.

Front 44

Which drug is a macrolide and more potent than cyclosporin?

Back 44

Tacrolimus

Front 45

Which drug causes hyperglycemia, glucose intolerance and diabetes mellutus?

Back 45

Tacrolimus: negative effect on pancreatic islet β cells. (more than cyclosporin)

Front 46

T/F: Cyclosporin A causes hyperurecemia and hyperlipidemia whereas tacrolimus dosen't.

Back 46

T.

Front 47

What are some drug interactions of tacromilus?

Back 47

1. synergistic effect with cyclosporin A.
2. P450 enzymes
3. mycophenolate mofetil

Front 48

Which drug complexes with FKBP but does not affect calcineurin activity?

Back 48

Sirolimus

Front 49

How is sirolimus transported?

Back 49

by P-glycoprotein

Front 50

Which is the drug to pick in combination with glucocorticoids and mycophenolate mofetil to avoid calcineurin inhibitors and kidney dysfunction?

Back 50

sirolimus

Front 51

What is the drug that can be incorporated into stents to inhibit local cell proliferation and blood vessel occlusion in coronary heart disease?

Back 51

sirolimus

Front 52

Which drug increases serum cholesterol and TG and lymphocele?

Back 52

sirolimus

Front 53

Which drug interfere with sirolimus?

Back 53

1. CYP3A4 substrates
2. drugs that transported by p-glycoprotein.
3. cyclosporin: renal dysfunction, hyperlipidemia, myelosuppression.

Front 54

T/F: Crohn's disease is mediated by Th2 response.

Back 54

F. Should be Th1.

Front 55

Which is the central inflammatory molecule in rheumatoid arthritis?

Back 55

TNF-α

Front 56

Name the six TNF-α inhibitors.

Back 56

1. Etanercept: binds both TNF-α,β, treats RA, psoriatic arthritis, ankylosing arthritis.
2. Infliximab: treats RA and unresponsive Crohn's.
3. Adalimumab: RA, psoriatic arthritis, HIV arthropathy, wasting.
4. Certolizumab pegol: Crohn's, RA
5. Thalidomide: under investigation.
6. TACE inhibitor: under investigation.

Front 57

Which class of drug does Infliximab belong to? List the toxicities.

Back 57

TNF-α inhibitors

infusion reaction
TB, UTI
anti-nuclear antibodies

Front 58

Which class of drug does Adalimumab belong to? List the toxicities.

Back 58

TNF-α inhibitors

infusion reaction
TB, UTI
anti-nuclear antibodies

Front 59

Which class of drug does Certolimuzab pegol belong to? List the toxicities.

Back 59

TNF-α inhibitors

headache, abdominal pain, cough, arthralgia
nasopharyngitis, UTI, influenza, TB
demyelinating disease

Front 60

Which class of drug does Etanercept belong to? List the toxicities.

Back 60

TNF-α inhibitors

injection site reactions
TB

Front 61

Which class of drug does Thalidomide belong to? List the toxicities.

Back 61

TNF-α inhibitors

teratogenic

Front 62

Which class of drug does TACE inhibitors belong to? List the toxicities.

Back 62

TNF-α inhibitors

liver toxicity

Front 63

Why pegylate Certolizumab?

Back 63

increases half life
water soluble
high motility
lack toxicity

Front 64

Name the IL-1 inhibitor.

Back 64

Anakinra: treats RA

Front 65

Name the IL-6 inhibitor.

Back 65

Tocilizumab: binds IL6 receptor, treats RA.

Toxicity: increased serum cholesterol, liver dysfunction, but no anti-DNA antibodies.

Front 66

Which class of drug does OKT3 belong to? List the toxicities.

Back 66

monoclonal antibody: against CD3 on CD4 and CD8 T cells.

Toxicities:
cytokine release syndrome.

Front 67

What is the drug to use when tranplant theray of cyclosporin A and glucocorticoids fail?

Back 67

OKT3

Front 68

Which class of drug does Declizumab and Basiliximab belong to? List the toxicities.

Back 68

monoclonal antibody: against CD25(IL-2 receptor) on T cells.

Toxicities:
hypersensitivity, neoplasia.

Front 69

Which drugs target CD25, part of IL2 receptor?

Back 69

Daclizumab, Basiliximab

Front 70

Which drugs target CD3?

Back 70

OKT3

Front 71

Which drugs target CD20 which is only expressed on B cells?

Back 71

Rituximab

Front 72

Which drug treats non-Hodgekins lymphoma and RA?

Back 72

Rituximab

Front 73

Which drugs target CD52 which is expressed on B, T, NK cells, monocytes, macrophages?

Back 73

Alemtuzumab

Front 74

Name the costimulation inhibitors.

Back 74

1. Alefacept
2. Abatacept
3. Belatacept
4. Belimumab
5. Anti-CD40L antibody

Front 75

T/F: CD28 activate B7 whereas CTLA4 inhibits it.

Back 75

T

Front 76

Which drugs target CD2 which interact with LFA3 on APCs?

Back 76

Alefacept: treat plaque psoriasis.

Front 77

Which drug target the B7 binding region on CTLA-4, thus prevents CD28 from activating B7?

Back 77

Abatacept: transpalnt therapy, RA.

Belatacept: similar, still under clinical trials.

Front 78

Which drug taget B lymphocyte stimulator BLYs/BAFF?

Back 78

Belimumab: SLE, RA

Front 79

Name the inhibitors of lymphocyte trafficking.

Back 79

1. Efalizumab
2. Natalizumab
3. FTY720

Front 80

Which class of drug does Efalizumab belong to? What is its action and therapeutic uses?

Back 80

lymphocyte trafficking inhibitior: anti LFA-1(CD11)
Treat psoriasis
Toxicity: infections.

Front 81

Which drug targets α4 intergrin (part of VLA4, LPAM1) on leukocytes and endothelial cells?

Back 81

Natalizumab: treat relasping-remitting multiple sclerosis.

Front 82

Which drug treats remitting multiple sclerosis?

Back 82

Natalizumab

Front 83

What is an agonist for sphigosine 1-phosphate receptor expressed on T and B cells?

Back 83

FTY720

Front 84

What is the function of sphigosine 1-phosphate receptor activation?

Back 84

sequesters lymphocytes into lymph nodes and Peyer's patches, away from circulation.

Front 85

What does FTY720 treat?

Back 85

Acute rejection.

Front 86

Which drug causes negative chronotropic effect on atrial myocytes?

Back 86

FTY720

Front 87

Which drugs treat IBD?

Back 87

AZA
Cyclosporin A

Front 88

Which drugs treat SLE?

Back 88

Anti-CD40L antibody (major)
Belimumab
Leflunomide
cyclosporin A

Front 89

Which drug treats myasthenia gravis?

Back 89

Leflunomide

Front 90

What are some anticancer drugs?

Back 90

Methotrexate
Cyclophosphamide

Front 91

What drugs treat psoriasis?

Back 91

Alefacept: severe form
Efalizumab
Methotrexate
Cyclosporin A

Front 92

Which drug is used for atopic eczema?

Back 92

calcineurin inhibitors

Front 93

What drug causes cytokine release syndrome?

Back 93

ATG/ALG
OKT3

Front 94

What drugs cause hypersensitivity?

Back 94

Daclimumab
Basilixumab

Front 95

Which drug causes aseptic menigitis?

Back 95

IGIV

Front 96

What drugs interact with cholestyramine?

Back 96

mycophenolate mofetil
leflunomide

Front 97

What do drugs that affect tubular secretion interfere with?

Back 97

mycophenolate mofetil
methotrexate

Front 98

List 2 drugs that bind to serum albumin.

Back 98

glucocorticoids
methotrexate

Front 99

Which drug interfere with aspirin?

Back 99

methotrexate

Front 100

Do calcineurin and mTOR inhibitors excrete in feces or in urine?

Back 100

Feces

Front 101

What drugs cause hypokalemia?

Back 101

tacrolimus
sirolimus (also cause hyperkalemia)

Front 102

Which drug is used to treat non-Hodgekin's lymphoma?

Back 102

Rituximab