Therapeutic Proteins -Fitz

Question 1

Disadvantage of cytokine therapy?

Answer 1

• extremely short half lives of drugs
• complicated nature of biological response invoked by these drugs
• extremely potent- unpredictable S.E

Question 2

Side effects of antibody therapy

Answer 2

1. Hypersensitivity
2. HAMA –>serum sickness
3. Infusion rxns/cytokine release syndrome: hypotension, respiratory distress
4. increased risk of infection

Question 3

Advantages to monoclonal antibodies:

Answer 3

• long half life
• specificity (magic bullet)
• Large # of potential targets

Question 4

Source Identifiers: 
u: 
o: 
xi: 
zu:

Answer 4

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

** less side effects with human, most with mouse

*exception: Abciximab= humanized

Question 5

Target: 
vir
bac
lim: 
les: 
cir:

Answer 5

vir: viral
bac: bacterial
lim: immune
les: infectious lesions
cir: cardiovascular

Question 6

Tumors:  
col:
mel:
mar:
got:
gov:
pr(o): 
tum:

Answer 6

col: colon
mel: melanoma
mar: mammory
got: testis
gov: ovary
pr(o): prostate
tum: misc

Question 7

2 design strategies:

Answer 7

1. Inhibition of protein function

2. Recruit immune system to attack cell.

Question 8

Symptoms of cytokine therapy?

Answer 8

General malaise

Unique, life threatening: IL-2
–> fatal hypotension

Question 9

Hematopoietic Agents –Erythroid Growth factors?

Answer 9

Darbepoetin
Erythropoietin
Methoxy Polyethylene Glycol Epoetin

Question 10

Hematopoietic Agents – Myeloid GFs:

Answer 10

Filgrastim (G-CSF) —> neutrophils
Pegrilgrastim
Sargramostim (GM-CSF) —>granulocytes and monocytes

Question 11

Hematopoietic Agents – Megakaryocyte GFs:

Answer 11

Interleukin 11
Romiplostim

*both stimulate platelet growth

Question 12

Erythroid Growth Factors:
MOA:

Pharmacokinetics:

Uses:

Answer 12

MOA: EPO–>RBC (works via JAK/STAT)

Pharm: short half life (give IV)

Uses: anemia (esp chronic kidney disease
–high risk surgery

Question 13

Don’t give Erythroid GF to?

Answer 13

• athletes

- MPEG-EPO –> to anemia caused by chemotherapy ( increased death)

Question 14

Erythroid Growth Factors: Side Effects

Answer 14

Life threatening – thrombus

Common – hypertension

Rare – increase tumor growth, allergic rxn

Question 15

Myeloid growth factors:
MOA:

Pharmacokinetics

Uses:

Answer 15

MOA: increase neutrophils (FIL), increase myeloid cells (SARG)

Pharm: PEG has longer half life

Uses: cancer chemotherapy

Question 16

S.E. of Filgrastim (G-CSF) and Pegfilgrastim

Answer 16

Rare: allergic rxns, splenic rupture

common: bone pain

Question 17

S.E. of Sagramostim (GM-CSF)

Answer 17

Common/serious: capillary leak syndrome=edema

Common/innocuous: bone pain, fever, malaise

Rare: allergic rxn

Question 18

Megakaryocyte GFs:

MOA:

Uses:

Answer 18

MOA: increase platelet production

Uses: cancer chemotherapy adjunt
-thrombocytopenia

**don’t use thrombopoeitin –>autoantibodies are produced

Question 19

S.E. of IL-11

doesn’t cause fever

Answer 19

Common/serious: A fib

Common/innocuous: fluid dyspnia, dizziness, fatigue, headache

Rare: hypokalemia

Question 20

Characteristics of current therapeutic proteins:

Answer 20

1. Lack of oral bioavailability
2. Generation of neutralizing antibodies
3. Lack of receptor specificity
   4 Short duration of action

Question 21

Longest half life?

Shortest?

Answer 21

Longest: monoconal antibodies

Shortest: cytokines (TNF)

Question 22

Infusion Rxn side effect of Ab tx:

Answer 22

Type I hypersensitivity
Immediate
-worse with repeated admin
-anaphylaxis

Question 23

Type III hypersensitivity side effect of Ab Tx:

Answer 23

7-10 days

• less with repeated injections
• —>serum sickness
• –>HAMA response

Question 24

Release syndrome?

Answer 24

S.E. Ab tx

- if you are trying to recruit immune system –> cytokine storm –>general malaise