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B29-31 Flashcards

1
Q

Alkylating agent used as immunosuppressive?

A

Cyclophosphamide

in organ transplantation and rheumatic diseases

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2
Q

what about cyclophosphamide?

A
  • nitrogen mustard

- CCNS

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3
Q

Antimetabolite that is used in immunosupressive agent?

A

methotrexate

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4
Q

what about methotrexate?

A

antagonists of folic acid

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5
Q

methotrexate MOA?

A
  • inhibitor of dihydrofolate reductase

- interferes with nucleic acid and protein metabolism

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6
Q

methotrexate pharmacoKinetix?

A
  • Oral and I.V.
  • good tissue distribution (except CNS)
  • not metabolized,
  • clearance is dependent on renal function
  • Adequate hydration is needed to prevent crystallization in renal tubules
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7
Q

Clinical uses of methotrexate as immunosupressive agent?

A
  • rheumatoid arthritis

- psoriasis

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8
Q

drug used in Kidney, Liver and heart transplantation?

A

Mycophenolate Mofetil

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9
Q

Mycophenolate Mofetil MOA

A
  • converted into mycophenolic acid –> inhibits inosine monophosphate dehydrogenase –> blocks GTP synthesis –> supresses both B and T lymphocyte activation
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10
Q

Mycophenolate Mofetil Clinical use?

A

kidney
Liver
heart transplantations

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11
Q

Mycophenolate Mofetil Toxicity?

A

G.I disturbances

neutropenia

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12
Q

cytotoxic drug used in IBD, rheumatic diseases and organ transplantation?

A

Azathioprine

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13
Q

Azathioprine MOA?

A

interferes with purine nucleic acid metabolism of immune cells

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14
Q

give example of disease modifying antirheumatoc drug?

A

leflunomide

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15
Q

Leflunomide MOA?

A

Inhibitor of dihydroorotate dehydrogenase –> inhibits pyrimidine synthesis –> interfere with the activity of T lymphocytes

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16
Q

Leflunomide administration?

A

orally

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17
Q

Leflunomide clinical uses?

A

rheumatoid arthritis

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18
Q

Inhibitors of cytokine gene expression, 5-ASA derivatives?

A 
cyclosporin A	
tacrolimus	
sirolimus	
tofacitinib	
sulfasalazine
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19
Q

Calcineurin and mTOR Inhibitors?

A

Cyclosporine
tacrolimus
sirolimus

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20
Q

Cyclosporine A MOA?

A

binds to cyclophilin –> inhibits calcineurin –> inhibits the production of IL-2,3 IFN-g

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21
Q

Tacrolimus MOA?

A

binds to FKBP –> inhibit calcineurin –> inhibits the production of IL-2,3 IFN-g

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22
Q

Sirolimus MOA?

A

binds to FKBP –> inhibit the kinase activity of mammalian target of rapamycin (mTOR) –> inhibits the T-cell proliferation response to IL-2

23
Q

Cyclosporine clinical use?

A
  • in solid organ transplantation
  • to prevent and treat graft-versus-host (GVH) disease in recipients of allogeneic stem cell transplantation
  • rheumatoid arthritis
  • uveitis
  • psoriasis
  • asthma
  • type 1 diabetes
24
Q

Tacrolimus clinical use?

A
  • in solid organ transplantation
  • to prevent and treat graft-versus-host (GVH) disease in recipients of allogeneic stem cell transplantation
  • rheumatoid arthritis
  • uveitis
  • psoriasis
  • asthma
  • type 1 diabetes

(same as cyclosporine)

25
Sirolimus Clinical uses?
Sirolimus-eluting stents are used to prevent restenosis after coronary angioplasty
26
Cyclosporine Pharmacokinetix?
- oral or intravenous - exhibits erratic bioavailability (serum lvls are routinely monitored) - slow hepatic metabolism by the cyt P450 system - long 1/2 life
27
Tacrolimus administration?
oral or I.V.
28
Sirolimus administration?
ONLY oral
29
Cyclosporine Toxicity?
- renal dysfunction - hypertension - neurotoxicity
30
Tacrolimus Toxicity?
- renal dysfunction - hypertension - neurotoxicity
31
Sirolimus Toxicity?
- hypertriglyceridemia - hepatotoxicity - diarrhea - myelosuppression
32
other drugs to know for topic immuno II
sulfasalazine tofacitinib (they are DMARDs)
33
Antibodies and fusion proteins in immunopharmacology?
``` ATG (antithymocyte-globulin) rituximab infliximab adalimumab tocilizumab ustekinumab natalizumab dupilumab abatacept ```
34
what is ATG?
AntiThymocyte Globulin
35
ATG MOA?
- bind to human T cells involved in antigen recognition --> initiate their destruction by serum complement - block cellular immunity --> suppress organ graft rejection
36
ATG clinical use?
- used before allogeneic stem cell transplantation to prevent graft-versus-host reaction - used in combination with other immunosuppressants for solid organ transplantation
37
ATG toxicity?
- hypersensitivity reactions: 1. serum sickness 2. anaphylaxis - Pain and erythema (injection sites) - lymphoma (late complication)
38
what about rituximab?
- DMARD | - monoclonal Ab that interfere with the activity of B lymphocytes
39
Rituximab MOA
binds to a surface protein CD20 on B lymph. in non-Hodgkin’s lymphoma cells then: - complement-mediated lysis - direct cytotoxicity - induction of apoptosis
40
Rituximab use?
- non-Hodgkin’s lymphoma | - rheumatoid arthritis (with methotrexate)
41
Rituximab toxicity?
- anemia - neutropenia - hypotension - fever
42
examples of MAbs that target TNF?
Infliximab | Adalimumab
43
Infliximab MOA?
against TNF-α --> thereby decreases formation of interleukins and adhesion molecules involved in leukocyte activation
44
Infliximab Clinical use?
- in treatment-resistant Crohn’s disease - rheumatoid arthritis (with methotrexate) - ulcerative colitis - psoriatic arthritis
45
Adalimumab MOA?
human IgG monoclonal antibody that binds to TNF-α
46
Adalimumab Clinical use?
rheumatoid arthritis
47
ustekinumab MOA?
Binds and neutralizes the biological activity of IL-12 & IL-23
48
ustekinumab Clinical use?
Plaque psoriasis
49
natalizumab MOA?
- Anti-Integrins | - Humanized IgG4 binds to integrins on leukocytes (except neutrophils)
50
Natalizumab Clinical use?
Drug resistant multiple sclerosis Crohn’s disease
51
What are the risks of using Natalizumab?
progressive multifocal leukoencephalopathy (PML)
52
dupilumab
u can skip it. its not in the book
53
Abatacept MOA?
blocks T-cell activation by interfering with the interaction of T-cell CD28 to APC
54
Abatacept Clinical use?
severe rheumatoid arthritis

mrts (19 decks)

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