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immunology - drugs Flashcards

1
Q

immunosuppressants - mechanism of action

A

agents that block lymphocyte activation and proliferation

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2
Q

immunosuppressants reduce acute transplant immunity by suppressing

A

cellular immunity

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3
Q

immunosuppressants - frequently combined to …

A

achieve greater efficacy with decreased toxicity

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4
Q

immunosuppressants - chronic suppression –>

A

high risk of: 1. infection 2. malignancy

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5
Q

immunosuppressants - drugs

A
  1. cyclosporine
  2. tacrolimus
  3. Sirolimus (Rapamycin)
  4. Daclizumab
  5. Basiliximab
  6. Azathioprine
  7. Mycophenolate mofetil
  8. Corticosteroids
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6
Q

Cyclosporine - mechanism of action

A

binds cyclophilin –> the complex inhibits Calcineurin (a TCR downstream protein that activates NFAT, a TF, through de-phosphorylation) –> prevent IL-2 transcription
–> blocks T cell activation

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7
Q

Cyclosporine - clinical use

A
  1. transplant rejection prophylaxis
  2. psoriasis
  3. RA
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8
Q

Cyclosporine - toxicity

A
  1. Nephrotoxity
  2. hypertension
  3. hyperlipidemia
  4. neurotoxicity
  5. gingival hyperplasia
  6. hirsutism
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9
Q

Tacrolimus - mechanism of action

A

binds FK506 –> the complex inhibits Calcineurin (a TCR downstream protein that activates NFAT, a TF, through de-phosphorylation) –> prevent IL-2 transcription
–> blocks T cell activation

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10
Q

Tacrolimus - clinical use

A

transplant rejection prophylaxis

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11
Q

Tacrolimus - side effects

A
  1. diabetes
  2. neuphrotoxic
  3. neuroticity
  4. hypertension
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12
Q

Tacrolimus and cyclosporine are both highly …. (side effect)

A

nephrotoxic

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13
Q

Sirolimus (Rapamycin) - mechanism of action

A

binds FKB –> the complex inhibits mTOR (IL-2R downstream) –> blocks T-cell activation and B-cell differentiation by preventing RESPONSE TO IL-2

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14
Q

Sirolimus (Rapamycin) - clinical use

A
  1. kidney transplant rejection prophylaxis

2. also used in drug-eluting stents

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15
Q

A drug-eluting stent (DES) is a

A

peripheral or coronary stent placed into narrowed peripheral or coronary arteries –> slowly releases a drug to block cell proliferation –> prevents fibrosis + clots –> prevent restenosis

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16
Q

Sirolimus (Rapamycin) - side effects

A
  1. pancytopenia
  2. insulin resistance
  3. Hyperlipidemia
    NOT NEPHROTOXIC
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17
Q

Sirolimus (Rapamycin) is NOT (toxicity)

A

nephrotoxic

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18
Q

Sirolimus (Rapamycin) act synergic with

A

cyclosporine

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19
Q

Daclizumab - mechanism of action

A

monoclonal antibody that blocks IL-2R

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20
Q

Basiliximab - mechanism of action

A

monoclonal antibody that blocks IL-2R

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21
Q

Daclizumab, Basiliximab - clinical use

A

kidney transplant rejection prophylaxis

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22
Q

Daclizumab, Basiliximab - side effects

A
  1. edema
  2. hypertension
  3. tremor
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23
Q

Azathioprine - mechanism of action

A

Antmetaboite precursor of 6-MP –> inhibit PRPP amidotransferase –> decrease de novo purine synthesis
–> inhibits lymphocyte proliferation

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24
Q

Azathioprine - toxicity

A
  1. Myelosuppresion
  2. GI. toxicity
  3. Liver toxicity
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25
Azathioprine and MP-6 are metabolized by
Xantine oxidase
26
Azathioprine - clinical use
1. Transplant rejection prophylaxis 2. RA 3. IBD 4. Glomerulonephritis 5. other autoimmune conditions
27
Mycophenolate mofetil - mechanism of action
Reversibly inhibits IMP dehydrogenase preventing purine synthesis of B and T cells
28
Mycophenolate mofetil - clinical use
1. Transplant rejection | 2. lupus nephritis
29
Mycophenolate mofetil - toxicity
1. GI upset 2. pancytopenia 3. hypertension 4. hyperglycemia 5. Associated with invasive CMV infecion LESS NEPHROTOXIC AND NEUROTOXIC
30
Corticosteroids as immunosuppressants - mechanism of action
1. Inhibit NF-kB --> suppress both B and T-cell function by decreased transcriptio nof many cytokines 2. induce apotptosis of T-lymphocytes
31
Corticosteroids as immunosuppressants - clinical use
1. Transplant rejection prophylaxis 2. many autoimmune disorders 3. many inflammatory disorders
32
Corticosteroids as immunosuppressants - toxicity
1. iatrogenic cushing 2. cataracts 3. avascular necrosis of femoral head
33
monoclanal antibodies against IL-2R
1. Daclizumab | 2. Basiliximab
34
recombinant cytokines - agents
1. Aldesleukin (IL-2) 2. erythropietin (epoetin alfa) 3. Filgrastim (G-CSF) 4. Sargramostim (GM-CSF) 5. IFN-α 6. IFN-β 7. IFN-γ 8. Oprelvekin (IL-11) 9. Romiplostim, eltrombopag (thrombopoietin receptor agonists)
35
erythropoietin (epoetin alfa) - clinical use
anemias (esp in renal failure)
36
Granulocyte-colony stimuating factor (G-CSF) - drug and clinical use
Filgrastim | Recovery of bone marrow
37
IL-2 - drug and clinical use
Aldesleukin --> 1. Renal cell carcinoma | 2. metastatic melanoma
38
Granulocyte/macrophage-colony stimuating factor(GM-CSF) - drug and clinical use
Sargramostin --> Recovery of bone marrow
39
interferons as drugs - clinical use
Interferons - α: 1. chronic hepatitis B, C 2. Kaposi sarcoma 3. hairy cell leukemia 4. condyloma acuminatum 5. renal cell carcinoma 6. malignant melanoma Interferons - β: multiple sclerosis Interferons - γ: chronic granulomatous disease
40
IL-11 - drug and clinical use
Oprelvekin --> thrombocytopenia
41
thrombopoietin receptor agonists - drugs and clinical use
Romiplostim, eltrombopag --> thrombocytopenia
42
immunosuppressants - drugs
1. cyclosporine 2. tacrolimus 3. Sirolimus (Rapamycin) 4. Daclizumab 5. Basiliximab 6. Azathioprine 7. Mycophenolate mofetil 8. Corticosteroids
43
Therapeutic antibodies for cancer (drug and target)
1. alemtuzumab --> CD52 2. bevacizumab --> VEGF 3. Cetuximab --> EGFR 4. Rituximab --> CD20 5. Trastuzumab (Herceptic) --> HER2/neu
44
Trastuzumab (Herceptic) - target and clinical use / toxicity
target: HER2/neu 1. HER-2 (+) breast cancer 2. Gastric cancer SE: cardiotoxicity
45
Bevacizumab - target and clinical use
target: VEGF (inhibits angiogenesis) 1. Colorectal cancer 2. renal cell carcinoma 3. Neovascular age-related macular degeneration (Ranibizumab, Bevacizumab)
46
Bevacizumab - side effects
1. hemorrhage 2. blood clots 3. impaired wound healing
47
Cetuximab - target and clinical use
target: EGFR 1. Stage IV colorectal camcer (Wild type KRAS) 2. head and neck cancer
48
Cetuximab - side effects
1. Rash 2. elevated LFTs 3. diarrhea
49
Rituximab - target / clinical use
target: CD20 1. B cel non-Hodgkin 2. CLL 3. RA 4. Idiopathic thrombocytopenic purpura (ITP) SE: increased risk for progressive multifocal leukoencephalopathy
50
alemtuzumab - target and clinical use
CD52 | 1. CLL 2. MC
51
Therapeutic antibodies for cancer (drug and target)
1. alemtuzumab --> CD52 2. bevacizumab --> VEGF 3. Cetuximab --> EGFR 4. Rituximab --> CD20 5. Trastuzumab (Herceptic) --> HER2/neu
52
Therapeutic antibodies for autoimmune disease therapy (drug and target)
1. Adalimumab --> Soluble TNF-α 2. Certolizumab --> Soluble TNF-α 3. Infliximab --> Soluble TNF-α 4. Eculizumab --> Complement protein C5 5. Natalizumab --> a4 integrin
53
monoclonal antibodies against TNF-α
1. Adalimumab 2. Certolizumab 3. Infliximab
54
monoclonal antibodies against TNF-α clinical use / SE
1. IBD 2. RA 3. Psoriasis 4. Ankylosing spondylitis SE: predispose to: infection, including reactivation of latent TB
55
Etanercept - mechanism of action
fusion protein (receptor for TNF-A+IgG1 FC) produced by recombinant DNA (A DECOY) --> not antibody
56
eculizumab - target and clinical use
target: C5 protein | paroxysmal noctural hemogloinuria
57
Natalizumab - mechanism of action
target α4-integrin -WBC adhesion
58
Natalizumab - clinical use
1. MS | 2. Crohn disease
59
Natalizumab - side effect
risk for PML in patients with JC virus
60
Abciximab - mechanism of action
monoclonal antibody against platelet glycoproteins IIb/IIIa
61
Abciximab - clinical use
antiplatelet agent for preventon of ischemic complications in patients undergoing percutaneous coronary intervention
62
Denosumab - mechanism of action / clinical use
monoclonal antibody against RANKL --> inhibits osteoclast maturation (mimics osteoprotegerin) clinical use: osteoporosis
63
Digoxin immun Fab - mechanism of action and clinical use
monoclonal antibody against Digoxin | Antidote for digoxin toxicity
64
Omalizumab - mechanism of action and clinical use
monoclonal antibody against IgE --> prevent IgE bidning to FCεRI allergic asthma
65
Palivizumab - mechanism of action / clinical use
monoclona antibody against RSV F protein | clinical use: RSV prophylaxis for high risk infants
66
monoclonal antibodies against VEGF
1. Ranibizumab | 2. Bevacizumab
67
monoclonal antibodies against VEGF - clinical use
1. Neovascular age-related macular degeneration (Ranibizumab, Bevacizumab) 2. Colorectal cancer (Bevacizumab) 3. renal cell carcinoma (Bevacizumab)
68
monoclona antibody against CD52 - drugs and clinical use
Alemtuzumab | 1. CLL 2. MS

Immunology (10 decks)

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