Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm > 2: Immunosuppressants > Flashcards

2: Immunosuppressants Flashcards

1
Q

what does immunopharmacology involve?

A
  • production of vaccines and immunization
  • treatment of inflammation
  • autoimmune disorders
  • allergies
  • fungal, viral, and bacterial infections
  • infections due to parasites
  • cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what induces autoimmune diseases?

A

hyperactive T cell immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what causes immune suppression and incompetence?

A

hypoactive response of T cell immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

role of each:

  • helper T cells
  • cytotoxic T cells
  • suppressor T cells
A

helper: coordination of immune response
cytotoxic: remove virus-infected cells from the body
suppressor: temper immune response when it’s overactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

purpose of immunosuppressants

A

inhibit normal immune response following organ transplantation or overactive immune response associated with autoimmune disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what part of the immune response do immunosuppressants work best for?

A

primary immune response

  • efficacy depends on the type of immune response
  • best results when treatment begun before exposure to Ag
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

define acute rejection

A
  • occurs 24h to weeks post transplant

- mediated by T cells and cytokine release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how is immunosuppression achieved?

A

different classes of immunosuppressants that:

  • decrease amount of lymphocytes
  • divert lymphocyte traffic
  • block pathways involved in lymphocytic response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

classes of immunosuppressants

A
  1. regulators of gene expression
  2. alkylating agents
  3. inhibitors of de novo purine synthesis
  4. inhibitors of de novo pyrimidine synthesis
  5. kinase and phosphatase inhibitors
  6. protein immunosuppressants
  7. others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what drugs are regulators of gene expression?

A

adrenocortical steroids - prednisone, prednisolone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what parts of immunosuppression are adrenocortical steroids used for?

A

induction and maintenance therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

function of adrenocortical steroids

A
  • reduce circulating lymphocyte levels
  • block lymphocyte activation required for Ag presentation
  • block T cell proliferation

(inhibit IL-2 gene expression, which is required for clonal expansion of B and T cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what drugs are alkylating agents?

A

cyclophosphamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what drugs are inhibitors of de novo purine synthesis?

A

azathioprine, 6-mercaptopurine (first gen)

mizoribine, mycophenolate mofetil (MMF) (second gen)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what parts of immunosuppression are alkylating agents and purine synthesis inhibitors used for?

A

induction and maintenance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

function of alkylating agents and purine synthesis inhibitors

A
  • block or interfere with DNA/RNA synthesis and function

- prevent clonal expansion of B and T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

chemically describe MMF

A

-ester prodrug -> active form: mycophenolic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

function of MMF

A

inhibits inosinse 5’-monophosphate DH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

side effects of MMF

A

GI shit and events related to bone marrow suppression (leukopenia, anemia, thrombocytopenia)

does NOT have CV risk or chronic nephrotoxic secondary effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what drugs are inhibitors of de novo pyrimidine synthesis?

A
  • brequinar
  • leflunomide
  • malononitrilamides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

MOA of de novo pyrimidine synthesis

A

inhibit dihydroorotate DH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

usefulness of the leflunomide derivative, FK778?

A

no benefit for using FK778 over MMF - also seems more difficult for patients to tolerate

23
Q

what drugs are kinase and phosphatase inhibitors?

A

cyclosporine
tacrolimus
sirolimus/rapamycin

24
Q

what parts of immunosuppression are kinase and phosphatase inhibitors used for?

A

induction and maintenance therapy (block signaling pathways that stimulate IL-2 production)

25
Q

where does cyclosporine come from?

A

the fungus Tolypocladium inflatum Gams

26
Q

how is cyclosporine administered? dosing?

A

IV or p.o.

given 4-24h before transplant, continued after with lower doses at weekly intervals

27
Q

where does cyclosporine concentrate?

A

in the red and white blood cells

28
Q

PK of cyclosporine

A

metabolized by liver

mainly excreted in feces

29
Q

toxicity of cyclosporine

A 
renal (proximal tubule) - limiting factor 
gingival (hyperplasia) 
neuronal 
some hepatic 
may induce systemic HTN
30
Q

MOA of cyclosporine

A

associates with calcineurin and inhibits its phosphatase activity, preventing translocation of NFAT members to nucleus, inhibiting production of lymphokines

also blocks JNK and p38 signaling pathways that are induced by antigen recognition in T cells

31
Q

what is tacrolimus and where does it come from

A

macrolide abx from Streptomyces tsukubaensis

32
Q

MOA of tacrolimus

A

binds cytoplasmic FK506 binding protein 12 (FKBP12), inhibiting phosphatase pathway of calcineurin

also inhibits JNK and p38 pathways

33
Q

admin of tacrolimus

A

IV or p.o.

not as widely distributed as cyclosporine, but 100x as potent

34
Q

PK of tacrolimus

A

metabolized in liver
mainly excreted in feces
produces similar toxicity to cyclosporine

35
Q

what specific disease is tacrolimus proposed to be beneficial for?

A

myasthenia gravis, notably to reduce corticosteroid burden

36
Q

where does sirolimus/rapamycin come from?

A

Streptomyces hygroscopicus

37
Q

MOA of sirolimus

A

inhibits calcineurin (and blocka response of T cells to cytokines) by binding FKBP12

but complex formation with FKBP12 does not inhibit IL-2 production in contrast to what happens with other drugs in this class

38
Q

admin of sirolimus

A

alone or in combo w/: cyclosporine, tacrolimus, or MMF

-efficacy improved when used with cyclosporine

39
Q

what drugs are protein immunosuppressive drugs?

A

antilymphocyte globulins:

  • muromonab-CD3
  • daclizumab
  • basiliximab

polyclonal antithymocyte globulin

anti-CD52 or anti-CD20 agents

belatacept

40
Q

antilymphocyte globulin MOA

A

inhibit acute graft rejection by binding to lymphocyte surface proteins

  • daclizumab/basiliximab = antiCD25 monoclonal Ab’s for induction and induce less T cell depletion than other drugs
  • muromonab = antiCD3 mouse monoclonal Ab that binds to T cell receptor-associated CD3 complex and alters T cells - used for induction and treatment of rejection
41
Q

what is belatacept and what is it equivalent to?

A

a targeted immunosuppressant drug -costimulatory blocker

equivalent alternative to traditional calcineurin inhibitors for kidney transplant recipients and for replacement of calcineurin inhibitors over time

42
Q

belatacept MOA

A

inhibits CD28-mediated T cell costimulation

high affinity mutant form of T-lymphocyte associated antigen 4-IgG1 (CTLA4Ig) that binds to CD80 and CD86 on APCs, blocking engagement of CD28 on T cells and preventing T cell activation

43
Q

what is special about belatacept?

A

seems to specifically target immune rxn against transplants

44
Q

AE of belatacept

A 
anemia
neutropenia 
UTI 
headache
peripheral edema 
more frequent post-transplant lymphoproliferative disorders compared to other immunosuppressants 
high cost  \$\$$ 
serious side effects in kids***
45
Q

what are the two most widely studied costimulatory pathways for studying induction or maintenance of allograft tolerance?

A

CD28/B7 and CD40/CD154 pathways

46
Q

what is rapamycine?

A

macrocyclic lactone from Streptomyces hygroscopicus

47
Q

MOA of rapamycine

A

targets mTOR (key regulator of cell proliferation)

48
Q

uses of rapamycine

A

-some for treatment of acute transplant rejection

**facilitates maintenance of cardiac and pulmonary transplants by preventing sm. mm. proliferation (in cardiac) and fibroblasts (in pulm) that are detrimental to the proper fxn of the transplanted organs

49
Q

what is everolimus and what is it used for?

A

a drug similar to rapamycine- used for renal transplantation b/c little nephrotoxicity
-also being tried in patients with neoplasia and renal insufficiency

50
Q

why can everolimus not replace calcineurin inhibitors?

A

b/c its use as sole “immunosuppressant” comes w/ de novo donor-specific alloantibodies associated with Ab-mediated rejection

so, proposed as a reduced dose in combo w/ calcineurin inhibitors

51
Q

what is fingolimod?

A

FTY720 - synthetic small molecule related to myricin, a sphingosine analog

52
Q

fingolimod MOA

A

reduced circulating T cells by driving them into lymphoid tissues

53
Q

fingolimod uses

A

mainly for MS since it reduces infiltration of lymphocytes into the CNS

54
Q

what can be used for rheumatoid arthritis?

A

TNF-a inhibitors

Pharm (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions