Pharmacology

Question 1

Antimetabolites - list ‘em! Go!

Answer 1

Methotrexate ( MTX)

5-flourouracil ( 5-FU)

Cytarabine

Azathioprine

6-mercaptopurine ( 6-MP)

6-thioguanine ( 6-TG)

**all are S phase specific**

Question 2

Methotrexate

Answer 2

folic acid analog that inhibits dihydrofolate reductase –> decrease dTMP –> decrease DNA and protein synthesis

Question 3

Methotrexate clinical uses

Answer 3

cancers: leukemia, lymphomas, choriocarcinoma

Non-neoplastic: abortion, ectopic pregnancy , etc.

Question 4

Methotrexate toxicity

Answer 4

myelosuppression

is reversible iwth leucovorin ( folinic acid)

Question 5

5-FU

Answer 5

pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid

this complex inhibits thymidylate synthase –> decreases dTMP –> decrease DNA and protein synthesis

Question 6

5-FU clinical use

Answer 6

colon cancer, basal cell carcinoma ( topical), pancreatic cancer

Question 7

5-FU toxicity

Answer 7

• myelosuppression
  
  • NOT reversible with leucovorin
  • overdose, rescue with uridine
• photosensitivity

Question 8

cytarabine

Answer 8

pyrimidine analog –> inhibition of DNA polymerase

for leukemias and lymphomas

Question 9

cytarabine toxicity

Answer 9

pancytopenia** - thrombocytopenia, megaloblastic anemia

Question 10

azathioprine, 6-MP, 6-TG

Answer 10

purine ( thiol) analog –> decrease de novo purine synthesis

Activated by HGPRT

Question 11

azathioprine, 6-MP, 6-TG clinical use

Answer 11

preventing organ rejection, SLE, lekeuma

irritable bowel syndrome ( IBL) - 6-MP, 6-TG

Question 12

azathioprine, 6-MP, 6-TG toxicity

Answer 12

6MP and azathioprine - myelosuppression

mech: both are metabolized by xanthine oxidase –> increased otxicity with allopurinol which inhibits their metabolism

Question 13

anti-tumor antibiotics - list ‘em! GO!

Answer 13

dactinomycine ( actinomycin D)

doxorubin, daunorubicin

Bleomycin

Question 14

Dactinomycin ( actinomycin D)

Answer 14

Mech: intercalates in DNA

Clinical use: wilms tumor, ewing sarcoma, used for childhood tumors ( children ‘act’ out)

Toxocity: myelosuppression

Question 15

doxorubicin, daunorubicin

Answer 15

mech: generates free radicals –> inctercalate in DNA –> breaks in DNA –> decrease replication
use: solid tumors, leukemia, lymphomas
toxicity: cardiotoxicity, myelsuppression, alopecia, toxic to cells following extravasation

**Dexrazoxane ( iron chelating agent) used to prevent cardiotoxicity **

Question 16

Bleomycin

p.404