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Year 2 Pharmacology > immunosuppressants > Flashcards

immunosuppressants Flashcards

1
Q

what are the indications for immunosuppressants?

A

transplantation - prophylaxis and acute rejection
autoimmune
inflammatory diseases

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2
Q

what are the major classes of immunosuppressive agents?

A

glucocorticoids
calcineurin inhibitors
antiproliferative / antimetabolic agents
biologicals

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3
Q

what are the adverse effects of immunosuppressive agents?

A

infectious disease

malignancy

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4
Q

what are the calcineurin inhibitors?

A

cyclosporine

tacrolimus

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5
Q

what are the antiproliferative / antimetabolic agents?

A

azathioprine
mycophenolate mofenil
sirolimus

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6
Q

what are the biological immunosuppressants?

A

antithymocyte globulin
muromonab-CD3
anti-TNFa

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7
Q

what are the general effects of glucocorticoids?

A

genomic - up to 1% of DNA influence via cytosolic receptors, inhibition of transcription factors

non-genomic - cell signaling pathways, cell membrane

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8
Q

what are the key specific effects of glucocorticoids?

A
  1. downregulation of proinflammatory cytokines (IL-1, IL-6)
  2. inhibit IL-2 (anti-T cell proliferation)
  3. decrease in peripheral WBCs
  4. reduce neutrophil chemotaxis
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9
Q

what are the adverse effects of glucocorticoids?

A 
growth retardation 
increased risk of infection 
poor wound healing 
hypertension 
avascular necrosis of bone 
cataracts 
hyperglycemia 
adrenal crisis upon rapid discontinuation
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10
Q

what is considered a low dose of glucocorticoid?

A

below 7.5 mg prednisone equivalent per day

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11
Q

what is considered a medium dose of glucocorticoid?

A

7.5 - 30 mg prednisone equivalent per day

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12
Q

what is considered a high dose of glucocorticoid?

A

30 - 100 mg prednisone equivalent per day

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13
Q

what is considered a very high dose of glucocorticoid?

A

over 100 mg prednisone equivalent per day

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14
Q

what is considered pulse therapy for glucocorticoid?

A

over 250 mg per day for 1 day or a few days

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15
Q

what drug is the standard for glucocorticoid dosing regimens?

A

prednisone

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16
Q

what is the MOA of cyclosporine?

A
  1. suppresses T cell immunity
  2. forms complex with cyclophilin, which then binds to calcineurin and eventually leads to prevention of transcription and translation of certain cytokines
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17
Q

what is the main adverse toxicity associated with cyclosporine?

A

nephrotoxicity

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18
Q

what is the preferred calcineurin inhibitor for transplantation due to ease of blood level monitoring?

A

tacrolimus

19
Q

what is the main therapeutic use for tacrolimus?

A

prophylaxis of allograft rejection in solid organ transplantation

20
Q

what are the main adverse effects of tacrolimus?

A

nephrotoxicity
HTN
diabetes
grapefruit

21
Q

what is the MOA of azathioprine?

A
  1. metabolized to 6-mercaptopurine
  2. metabolites incorporated into DNA
  3. inhibition of lymphocyte proliferation (lymphocytes do not have a salvage pathway)
22
Q

what are the adverse reactions of azathioprine?

A

bone marrow suppression
hepatotoxicity
VZV, HSV

23
Q

what is the MOA of mycophenolate mofetil?

A
  1. knock out de novo synthesis of guanine nts

2. inhibits lymphocyte proliferation

24
Q

what are the therapeutic uses for mycophenolate mofetil?

A

propylaxis for graft rejection

SLE

25
Q

what are the adverse reactions of mycophenolate mofetil?

A

hematologic
GI
contraindicated for pregnancy

26
Q

what is the MOA of sirolimus?

A

inhibits T cell proliferation via prevation of mTOR activation

27
Q

what drug has allowed combination use with cyclosporine and tacrolimus?

A

sirolimus

28
Q

what is the main therapeutic use of sirolimus?

A

renal transplant patients that cant tolerate calcineurin inhibitors due to high-risk nephrotoxicity

29
Q

what is the MOA of antithymocyte globulin?

A
  1. antibodies that bind to CDs (especially CD3) and HLAs on T cells
  2. depletion of circulating T cells via a) complement cytotoxicity and b) prevention of T cell activation
30
Q

what is the MOA of muromonab CD3?

A

anti-CD3 antibodies cause depletion of T cells

31
Q

what is the main therapeutic use of muromoab CD3?

A

reversal of glucocorticoid resistant organ transplant rejection episodes

32
Q

what is the main adverse reaction of muromonab CD3?

A

cytokine storm

33
Q

what is the MOA of the anti-TNFa reagents?

A

binds directly and prevents TNFa from binding to its receptors

34
Q

what are the anti-TNFa agents?

A

infliximab
adalimumab
etanercept

35
Q

what are the therapeutic uses of the anti-TNFa agents?

A

RA

IBD

36
Q

what class of drug is cyclosporine?

A

calcineurin inhibitor

37
Q

what class of drug is tacrolimus?

A

calcineurin inhibitor

38
Q

what class of drug is azathioprine?

A

antiproliferative / antimetabolite

39
Q

what class of drug is mycophenolate mofenil?

A

antiproliferative / antimetabolite

40
Q

what class of drug is sirolimus?

A

antiproliferative / antimetabolite

41
Q

what class of drug is antithymocyte globulin?

A

biologic

42
Q

what class of drug is muromonab-CD3?

A

biologic

43
Q

what class of drug is anti-TNFa?

A

biologic

Year 2 Pharmacology (70 decks)

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