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IHO 2 > Therapeutic proteins > Flashcards

Therapeutic proteins Flashcards

1
Q

Advantages of monoclonal antibodies

A
  • Long half-life
  • Specificity
  • Large # of potential targets.
  • Help for diagnostics and design disease process
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2
Q

Disadvantages of monoclonal antibodies

A
  • Hypersensitivity reactions (esp. human-mouse antibody reactions)
  • Infusion reactions/Cytokine release syndrome
  • Infections (esp. TB reactivation)
  • Effects on immunizations, cancer, fertility/pregnancy, birth defects???
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3
Q

Major disadvantages of cytokine therapy

A
  • Extremely short half-lives
  • Complicated nature of biological response
  • Extremely potent with potential for unpredicatible/undesirable side effects
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4
Q

What is the dose-limiting complication of many antineoplastic drugs?

A

Bone marrow suppression.

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5
Q

Fusion proteins

A

Joining of 2+ proteins in a novel way

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6
Q

Can fusion proteins occur naturally?

A

Yes. Ex. CML–> BCR-ABL

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7
Q

Problems with using native peptides

A
  • Lack of receptor specificity
  • Lack of oral bioavailability (must inject many of these proteins)
  • Generation of Ab againt proteins
  • Relative short duration of action
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8
Q

Solutions to help counteract problems with using native peptides

A
  • Add polyethlyene glycol (PEG)–> increases 1/2 life by masking protein from immune system
  • Use Ab structure as scaffold with no immune recruitment (increase 1/2 life)
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9
Q

Characteristics of ideal therapeutic Ab

A
  • High affinity and specificity
  • If goal is to recruit immune system, need adequate recruitment of effectors
  • Long 1/2 life
  • Few side effects
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10
Q

Monoclonal Ab administration

A

Given IV

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11
Q

Chimeric

A
  • 30-35% mouse

- more side effects

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12
Q

Humanized

A
  • 10% mouse
  • Fewer side effects
  • hyper variable region
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13
Q

Human

A
  • Fully human

- Fewest side effects

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14
Q

Infusion reactions/cytokine release syndrome

A

Chills, fever, arthralgia, diarrhea, vomiting, hypertension, respiratory distress,

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15
Q

Nomenclature

A

[drug company] [target] [source] [mab ending]

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16
Q

Source identifiers

A

u=human
o=mouse
xi=chimeric
zu=humanized

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17
Q

What does knowing the source of an Ab allow you to do?

A

Predict the severity of possible side effects

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18
Q

General disease or target

A 
vir=viral
bac=bacterial
lim=immne
les=infectious lesions
cir=cardiovascular
19
Q

Tumors

A 
col=colon
mel=melanoma
mar=mammary
got=testis
gov=ovary
pr(o)=prostate
tum=misc
20
Q

Typical fusion protein ending

A

-cept

21
Q

2 design strategies for monoclonal Ab

A
  1. Inhibiting protein function

2. Recruit immune system to all

22
Q

3 themes for multiple Abs

A
  1. same target–> multiple disease (e.g VEGF)
  2. different Ab–> same target (different companies)
  3. couple cytotoxic agents to increase effectiveness
23
Q

Common side effects of cytokines drugs

A

Anorexia, flu-like symptoms, general malaise, fatigue and can have life-threatening side effects

24
Q

IL-2 side effects

A

diarrhea, thrombocytopenia, shock, respiratory distress, coma, fatal hypertension

25
Q

Erythroid growth factor drugs

A

Darbepoietin, erythropoietin, methoxy polyethylene glycol epoietin

26
Q

Myeloid growth factor drugs

A

Filgrastim (G-CSF), Pegfilgrastim, sargramostim (GM-CSF)

27
Q

Megakaryocyte growth factors

A

IL-11, Romiplostim

28
Q

Mechanism of action of erythroid growth factors

A

EPO–>RBCs

  • produced in kidney
  • work through JAK/STAT activation
  • inverse relationship between [EPO] and hematocrit normally (ex. chronic renal failure)
29
Q

Erythroid growth factors pharmacokinetics

A

EPO-short half-life–>give 3-4x/wk IV

DAPBE–> give weekly
MPEG-EPO–> biweekly

30
Q

Therapeutic uses of erythroid growth factors

A

Anemia (esp. chronic kidney disease +folate/iron)

High risk surgery

31
Q

When not to give erythroid growth factors

A

Athletes

Anemia caused by chemo

32
Q

Life threatening side effect of erythroid growth factors

A

Thrombus formation

33
Q

Other side effects of erythroid growth facotrs

A

Hypertension (common serious), increased tumor growth, allergic reaction (rare serious)

34
Q

Myeloid growth factor mechanism of action

A

Filgrastim–produce neutrophils

Sagramostim–produces any myeloid cells

35
Q

Myeloid growth factor pharmacokinetics

A

PEG-FIL–> longer half-life

36
Q

Therapeutic uses of myeloid growth factors

A

Cancer chemotherapy

37
Q

Filgrastim(G-CSF), pegfilgrastim side effects

A

Allergic reactions, splenic rupture (rare serious). Mild-mod. bone pain (common innocuous)

38
Q

Sagramostim (GM-CSF)

A

Capillary leak syndrome, edema (common serious), mod. to severe bone pain, fever, malaise, myalgias (common innocuous). Allergic reactions (rare serious)

39
Q

Megakaryocyte growth factors mechanism of action

A

-Increase platelet production

40
Q

What megakaryocyte growth factor should you never use because antibodies are produced?

A

Thrombopoietin

41
Q

Pharmacokinetics of romiplostim

A

3-4 days

42
Q

Therapeutic uses for megakaryocyte growth factors

A

Cancer chemo adjunct

Thrombocytopenia

43
Q

Side effects of megakaryocyte growth factors

A
  • A fib (common serious)
  • Fatigue, headache dizziness, mild edema–>fluid dysphena and anemia (hemodilution) (common innocuous)
  • Hypokalemia (rare serious)
44
Q

Does IL-11 cause fever?

A

No

IHO 2 (6 decks)

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