Oncology Drugs

Question 1

Methotrexate
MOA
SE

Answer 1

Folic acid analog
Blocks DHF which reduces dTMP, DNA and protein synthesis

SEs: Myelosuppression think cytopenias, infections; this is reversible with Leucovorin
Fatty liver change
Mucositis (mouth ulcers)
Teratogenic

Question 2

How do you reverse myelosuppression due to MTX?

Answer 2

Leucovorin

Question 3

What is 5-FU
MOA
SE?

Answer 3

Pyrimidine analog thats activated to 5F-dUMP–>complex with Folic Acid

Complex blocks THYMIDYLATE SYNTHASE, which decreases dTMP, DNA, and protein synthesis

SEs: Myelosuppression (but not reversible with Leucovorin)

Rescue with Uridine instead

Photosensitivity

Question 4

Cytarabine (arabinofuranosyl cytidine)
MOA
SE

Answer 4

Pyrimidine analong that blocks DNA polymerase

SE: Pancytopenia incl throbocytopenia and megaloblastic anemia

Question 5

What is Azathiprine, 6-MP, 6-TP (thioguanine)

Answer 5

Purine analogs that block de nove purine synthesis

Activated by HGPRT, turns them into active metabolites that are inactivated by XO.

Dont take these with Allopurinol bc it blocks XO and then these will build up to toxic levels (except for 6-TG)

SE: Bone marrow, GI, Liver

Question 6

What are the anti-metabolites and where do they act?

Answer 6

Methotrexate, 5-FU, Cytarabine, Azathioprine, 6-MP, 6-TG

Work in the S phase

Question 7

What are the anti-tumor antibiotics?

Answer 7

Dactinomycin (actinomycin-D)
Doxurubicin (Adriamycin)
Daunorubicin
Bleomycin

Question 8

Dactinomycin
MOA
SE

Answer 8

Intercalates in DNA
Used for childhood tumors (Wilms, Ewing, Rhabdo)

SE: Myelosuppression

Question 9

Doxorubicin/Daunorubicin
MOA
SE

Answer 9

Intercalate into DNA
Generate free radicals
Cause breaks in DNA, blocking replication

Dilated Cardiomyopathy (use Dexrazoxane to prevent this)
Myelosuppression, alopecia

Question 10

what can be used to prevent cardiotoxicity (dialated cardiomyopathy) from doxo/daunorubicin?

Answer 10

Dexrazoxane which is an Fe chelating agent

Prevents free radical formation

Question 11

Bleomycin
MOA
SE

Answer 11

Induce free radical formation–>breaks in DNA strands

Use in Hodgkins/Testicular

SE: Pulmonary Fibrosis
Minimal myelosuppression
skin changes and mouth sores

Works in G2 phase

Question 12

What are the alkylating agents?

Answer 12

Cyclophosphamide, Ifosfamide, the Nitrosureas (carmustine, lomustine, semustine, streptozosin) and Bisulfan

Question 13

Cyclophosphamide
Ifosfamide

MOA
SE

Answer 13

Covalently link DNA at Guanine N-7
Has to be activated in the liver first

Myelosuppression esp myelodysplastic syndrome

But most importantly is HEMORRHAGIC CYSTITIS, prevent with MESNA bc it binds acrolein

SIADH

Question 14

What can be used to treat hemorrhagic cystitis from cyclophosphamide/ifosfamide?

Answer 14

Mesna

Question 15

What are the nitrosureas?

Answer 15

The mustines?

Carmustine, Lomustine, Semustine, Streptozocin

Question 16

How do the Nitrosureas work?

SE?

Answer 16

Cross link DNA, and can X BBB, but requires bioactivation first

SE:
Obviously CNS toxicity ie convulsions, dizziness, ataxia

Question 17

Busulfan
MOA
SE?

Answer 17

X-Links DNA

Used for CML

Severe myelosuppression
Pulmonary fibrosis
Hyperpigmentation

Question 18

What are the microtubule inhibitors?

Answer 18

Vincristine, Vinblastine, Paclitaxel, other TAXOLS

Question 19

Vincristine, Vinblastine
MOA
SE

Answer 19

Bind B tubulin, prevents spindle formation

blasts the spindle, M-phase arrest

Vincristine-neurotoxicity (areflexia, peripheral neuritis) and paralytic ileus, no myelosuppression

Vinblastine blasts bone so causes myelosuppression

Question 20

Paclitaxel, taxols, Docetaxel
MOA
SE

Answer 20

Hyperstabilizes polymerized microtubules in M phase

Spindle CANT BREAK DOWN

Myelosuppression, alopecia, HSR

Question 21

Cisplatin, Carboplatin

Answer 21

X-link DNA

SE Nephrotox, CN8 damage

Prevent nephrotox with Amifostine and Cl-diuresis

Question 22

What is Amifostine needed for?

Answer 22

Fix nephrotox from Cisplatin or carboplatin. Use with Cl- diuresis

Its a free radical scavenger

Question 23

Etoposide, Teniposide
MOA
SE

Answer 23

Etwoposide Topo two Inhibitor

SE: myelosuppresson, GI irritation, alopecia

Question 24

Irinotecan, Topetecan
MOA
SE

Answer 24

Inhibit Topo I
Prevent DNA unwinding and replication

SE: SEVERE MYELOSUPPRESSION, diarrhea

Question 25

Hydroxyurea
MOA
SE

Answer 25

Blocks ribonucleotide reductase which decreases DNA synthesis

S-phase specific

Melanoma, CML, sickle cell

Myelosuppression, GI Upset

Question 26

Prednisone, Prednisolone
MOA
SE

Answer 26

Triggers apoptosis
These two glucocorticoids used in CA

Can cause cushings, cataracts, acne, peptic ulcers

Question 27

Tamoxifen, Raloxifene
MOA
SE

Answer 27

SERMs
Estrogen Receptor antagonist in breast but agonist in bone (Raloxifene)

Tamoxifen causes endometrial CA, raloxifene prevents it

Question 28

Trastuzumab (Herceptin)
MOA
SE

Answer 28

Mab against Her2Neu which is a tyrosine kinase receptor (EGFR)

Used for breast AND GASTRIC CA so it treats 2 cancers (tras2zumab)

SE Cardiotox…heartceptin ~herceptin

Question 29

Imatinib
MOA
SE

Answer 29

Tyrosine kinase inhibitor of bcr-abl from CML and c-kit which is in GI stromal tumors

Causes fluid retention, myalgias, diarrhea

Question 30

Rituximab
MOA
SE

Answer 30

Mab against CD20+ which are B cells

Non Hodkins, RA with MTX, ITP

SE: incr risk for PML (progressive mulifocal leukoencephalopathy) which is demyelination associated with JC virus. also incr risk with natalizumab

Question 31

Vemurafenib
MOA
SE

Answer 31

Inhibits B-Raf kinase that has a V600E mutation

Use for metastatic melanoma

Question 32

Bevacizumab
MOA
SE

Answer 32

Mab against VEGF–>inhibits angiogenesis

SE: Hemorrhage and impaired wound healing