Brainscape's Knowledge GenomeTM

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


See full index

IHO Week 2 > Therapeutic Proteins > Flashcards

Therapeutic Proteins Flashcards

1
Q

Why are antibodies receiving attention as “personalized therapies”?

A
  1. Their specificity

2. Large number of potential targets

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

What do therapeutic cytokines do?

A

Stimulate the immune system

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

What do MABs do?

A
  1. Can stimulate/inhibit the immune system

2. Can block receptors

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

What is NOT a characteristic of therapeutic proteins?

A

Oral bioavailability - these proteins are broken down in the stomach

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

What are characteristics of therapeutic proteins?

A
  1. Generation of neutralizing antibodies
  2. Lack of receptor specificity
  3. Short duration of action
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What therapeutic proteins have very short and very long half lives?

A

Cytokines-Extremely short half-life! (acts in minutes, acts in limited space in body)
Monoclonal Antibodies - extremely long half life - remain in the body for a long time!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What drug has an extremely short half life?

A

Tumor necrosis factor

  • usually injected in body right near tumor because it degrades so fast (within minutes!)
  • shorter than -mab, and drug with Peg added
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does PEG do when you add it to a drug?

A

It stops the body from degrading it so well/so fast.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Is a human antibody always a better option than a humanized or chimeric antibody?

A

NO!

  • Specificity of Ab can vary
  • Is killing cells (recruiting immune system) the goal?
  • If stimulating the immune system is your goal, then a chimeric antibody would be better
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What must the names of monoclonal antibodies end with?

A

-MAB

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

What is the difference between human and humanized antibodies?

A

Humanized - still has 5% mouse protein in CDR region

Human - 100% human protein

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

What does a drug with Tu in the middle target?

A

Tumor

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

What does a drug with Ci in the middle target?

A

Circulatory system

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

What does a drug with Li in the middle target?

A

Immune system

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

What source does a drug with Xi in the middle-end come from?

A

Chimeric

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

What source does a drug with zu in the middle-end come from?

A

Humanized

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

What sourse does a drug with o in the middle come from?

A

Mouse

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

What source does a drug with u in the middle come from?

A

Human

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

What is the side effect severity of sources from least to most severe?

A

Human

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

What would you expect to see as a side effect of antibody treatment?

A
  1. Type III hypersensitivity reactions
  2. HAMA response
  3. Serum sickness
  4. Infusion reaction
  5. Cytokine release syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

You are planning to treat a patient who has irritable bowel disease with infliximab. What test should you perform first?

A

Mantoux test - need to screen before these drugs are given because they can “reactivate” latent/dormant infections - (similar to a hypersensitivity reaction!)

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

What are the three erythroid growth factors?

A
  1. Darbepoietin
  2. Erythropoietin
  3. M-PEG-EPOETIN
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the three classes of hematopoietic agents we need to know? What are they often used for?

A
  1. Erythroid Growth Factors
  2. Myeloid Growth Factors
  3. Megakaryocytic Growth Factors
    - Supportive agents given in lots of different type of cancer
24
Q

What are the three Myeloid growth factors you need to know?

A
  1. Filgrastim (G-CSF)
  2. Pegfilgrastem
  3. Sargramostem (GM-CSF)
25
Q

What are the two Megakaryocyte Growth Factors you need to know?

A
  1. Interleukin-11

2. Romiplostim

26
Q

What types of growth factors cause more side effects/problems?

A

Those that act earlier in the process (higher in the differentiation tree!)

27
Q

Where is the site of action for erythropoietin?

A

Between the erythroid progenitor and the erythrocyte

28
Q

Where is the site of action for filgramostim (G-CSF)?

A

Between Granulocyte-monocyte progenitor and neutrophils

29
Q

What is the site of action for Interleukin-11?

A

Between the common myeloid progenitor and megakaryocyte

30
Q

What is the site of action for sargramostim?

A
  • Between the common myeloid progenitor and all myeloid cells (erythroid, megakaryocytic, basophil, eosinophil, granulocyte-monocyte progenitors)
  • Between Granulocyte-monocyte progenitor and neutrophils & monocytes
31
Q

What are two side effects that are not specific to one growth factor but applies to many?

A
  1. General malaise

2. Allergic reactions

32
Q

What is the specific, serious side effect associated with Erythropoietin?

A

Hypertension & Thrombosis

33
Q

What is the specific, serious side effect associated with Filgramostim?

A

Splenic rupture, Bone pain

34
Q

What is the specific, serious side effect associated with Interleukin-11?

A

Atrial fibrillation

35
Q

What are the specific, serious side effects associated with Sargramostim?

A

Capillary leak syndrome and bone pain (worse than filgramostim!)

36
Q

What is the major advantage and drawback of monoclonal antibodies?

A

Advantage: long half-life
Drawback: Hypersensitivity reactions, in particular human anatomies antibody (“HAMA”) reactions

37
Q

What are the two major disadvantages to cytokine therapy?

A
  1. Extremely short half-lives of drugs

2. Complicated nature of the biological response invoked by cytokines

38
Q

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

A

Bone marrow suppression

39
Q

What has been developed to combat bone marrow suppression?

A

Recombinant forms of several colony stimulating factors

40
Q

What are fusion proteins?

A
  • Joining of two or more proteins together in a novel way
  • Can see naturally occurring Fps
    e. g. Chronic myeloid leukemia (BCR-ABL)
41
Q

What is the problem with using native/naturally occurring peptides as therapeutic proteins?

A
  1. Lack of receptor specificity (can use it to target many things, not just one)
  2. Lack of oral bioavailability (must inject)
  3. generation of antibodies against the protein
  4. Short duration of action –> degraded/cleared
42
Q

How can we solve the problem of degradation/elimination when using naturally occurring therapeutic proteins?

A
  • Add a PEG (polyethylene glycol) –> Long half life & “masks” protein from immune system
  • Use antibody structure as scaffold w/no immune recruitment –> High t1/2 (half life)
43
Q

What is the advantages of using Monoclonal antibody therapy?

A
  1. Specificity (“magic bullet”)
  2. Large # of potential targets
  3. Potential for long term benefit with short term treatment (if Abs stay & become incorporated into the immune system)
  4. Diagnostics - can use Abs to screen tissue - can tell if cancer is expressing protein Abs will respond to
  5. Define disease process –> can help you tell what subtype of disease the patient has
44
Q

What are the approved PEG’d Drugs?

A 
L-asparaginase
PEG-liposome containing doxorubicin
Interferon alpha
Methoxy polyethylene 
Glycol epoetin
Pegfilgrastim
45
Q

What are characteristics of an ideal therapeutic antibody?

A
  1. High affinity & target specificity
  2. If goal is to recruit immune system, must have adequate recruitment of effectors
  3. long t1/2 - don’t want immune system to target your Ab
  4. Few side effects
46
Q

What route of administration should be used for monoclonal antibodies and fusion proteins?

A
  • Give IV

- Has long t1/2

47
Q

What are common side effects of monoclonal Abs and fusion proteins?

A
  1. Hypersensitivity Rxn: fever, headache, anaphylaxis
  2. HAMA hypersensitivity + kidney –> serum sickness (human response hypersensitivity to human antimouse antibody)
  3. Infusion reactions/cytokine release syndrome: chills, fever, arthralgia, diarrhea, vomiting, hypotension, respiratory distress
  4. Infection: esp. when goal is to suppress immune systems => reactivation of TB (esp. anti-TNFalpha agents)
  5. ??? Immunizations, carcinogenesis, fertility, pregnancy –> birth defects?? => anti-TNFalpha [thalidomide]
48
Q

What is the general nomenclature for naming monoclonal Abs?

A

[Drug company] + [Target] + [Source] + [MAB]

49
Q

What are the common source identifiers for u, o, xi and zu?

A

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

50
Q

What are the general diseases or targets for the drugs that contain vir, bac, lim, les, cir?

A 
vir - viral
bac - bacterial
lim - immune
les - infectious lesions
cir - cardiovascular
51
Q

What are the general target abbreviations for drugs that contain col, mel, mar, got, gov, pr(o), tum?

A 
col - colon
mel - melanoma
mar - mammary
got - testis
gov - ovary
pr(o) - prostate
tum - misc
52
Q

What do fusion proteins end with?

A

-cept

53
Q

What are two design strategies for monoclonal Abs?

A
  1. Inhibition fo protein fxn

2. Recruit immune system to attack cell

54
Q

What are three themes for monoclonal Abs?

A
  1. Same target –> multiple diseases (e.g. VEGF can be used for colon cancer and macular degeneration)
  2. Different Abs –> same target (diff. drug company)
  3. Couple cytotoxic agents to Inc. effectiveness
55
Q

What are the two main “pitfalls” of using cytokine therapies?

A
  1. Extremely short half lives (minutes)
    - hard to maintain therapeutic [ ]
    - either give SC (subcutaneous) or IA (inter arterial)
  2. Extremely potent –> compliment cascades –> release other cytokines –> unpredictable/undesirable side effects
56
Q

What are some common side effects of cytokine use?

A
  • Anorexia, fever, flu-like symptoms, fatigue
  • GENERAL MALAISE
  • Can have unique, life threatening side effects: IL-2: diarrhea, thrombocytopenia, shock, respiratory distress, coma
  • FATAL HYPOTENSION
57
Q

What are hematopoietic agents (colony stimulating factors) used in conjunction with?

A

Chemotherapy!

IHO Week 2 (12 decks)

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