Antineoplastic Drugs

Question 1

Cyclophosphamide toxicity

Answer 1

Cardiotoxicity
hemorrhagic cystitis - bladder burn
Hematuria

Question 2

Sodium 2-mercaptoethane sulfonate role is to

Answer 2

MESNA’s role is to detoxify acrolein which is causes toxicity like (hemorrhagic cystitis + hematuria)

Question 3

Alkylating Agents MOA

Answer 3

alkylating DNA guanine = cross-linking stands –> apoptosis

Question 4

Platinum complexes MOA

Answer 4

covalent cross-linking of G-C base pairs = bend DNA

Question 5

Cisplatin toxicity

Answer 5

Renal damage = reduced with hydration
Ototoxicity
Hearing loss 
Tinnitus 
Peripheral Sensory Neuropathy

Question 6

Antimetabolites MOA

Answer 6

Block DNA formation –> abnormal DNA
Cell cycle dependent
Inhibits protein synthesis

Question 7

Methotrexate MOA

Answer 7

competitive inhibitor of dihydrofolate reductase
blocks dTMP
stops folate-dependent enzymes of de novo purine & thymidylate synthesis

Question 8

Methotrexate toxicity

Answer 8

nephrotoxicity
hepatic necrosis
bone marrow depression

Question 9

What can reduce Methotrexate toxicity?

Answer 9

Leucovorin by reducing folate (5-formylretrahydrofolate)

Question 10

Fluorouracil MOA

Answer 10

STOP DNA synthesis
converted to the fraudulent F-dUMP
F-dUMP forms a covalent complex with thymidylate synthase & methylene tetrahydrofolate (THF)

Question 11

what impacts 5-FU levels

Answer 11

DPYD/DPD

Question 12

Fluorouracil toxicity

Answer 12

severe ulceration of oral & GI mucosa + diarrhea

Question 13

Leucovorin Calcium MOA

Answer 13

its folinic acid which binds & stabilizes ternary complex of 5-fdUTP & thymidylate synthase = increases fluorouracil cytotoxicity

decreases the effects of methotrexate

Question 14

Leucovorin Calcium toxicity

Answer 14

diarrhea when given with fluorouracil

Question 15

6-Mercaptopurine MOA

Answer 15

blocks purine (guanine) synthesis 
Triphosphate form incorporated into DNA --> strand breaks

Question 16

6-Mercaptopurine toxicity

Answer 16

bone marrow depression

Xanthine oxidase inhibitors (Allopurinol) = increases effects

Question 17

Xanthine oxidase & TPMT (thiopurine methyltransferase) role is to

Answer 17

metabolize 6-Mercaptopurine in the liver

Question 18

Tumor cell lysis Syndrome is treated with

Answer 18

Allopurinol

Question 19

Mutations in TPMT =

Answer 19

drug accumulation + bone marrow destruction (infection)

Question 20

What is needed for 6-mercaptopurine activation

Answer 20

HGPRT = hypoxanthine guanine phsophoribosyl transferase

Question 21

Cytarabine (Pyrimidine Analog) MOA

Answer 21

inhibits DNA chain elongation + base rotation

Inhibits DNA polymerase

Question 22

Asparaginase MOA

Answer 22

Hydrolyze asparagine to aspartic acid & ammonia

Question 23

Asparaginase toxicity

Answer 23

risk of anaphylaxis

Question 24

Microtubule Inhibitors + MOA

Answer 24

Taxanes

• Paclitaxel (Paclitaxel)
• Docetaxel (Taxotere)

Arrest in Metaphase = blocks cell in mitosis

Question 25

Taxanes toxicity =

Answer 25

bone marrow toxicity | peripheral sensory neuropathy (dose limiting)

Question 26

Vinca Alkaloids

Answer 26

bind to b-tubulin & blocks polyermization with a-tubulin in the microtubules

Question 27

Anthracycline Antibiotics

Answer 27

inhibits resealing of DNA nicks by blocking Topoisomerase 2

Question 28

Anthracycline Antibiotics + Doxorubicin MOA

Answer 28

inhibits resealing of DNA nicks by blocking Topoisomerase 2

Question 29

Anthracycline Antibiotics + Doxorubicin Toxicity

Answer 29

Acute cardiac = arrhythmias (ST&T waves) | chronic cardiac = (cardiomyopathy --> CHF)

Question 30

Doxorubicin MOA for toxicity

Answer 30

free radical damage = generation of Hydroxyl radicals from peroxide

Question 31

that is the role of Dexrazoxane

Answer 31

to protect from cardiotoxicity

Question 32

Irinotecan MOA + Toxicity + Usages

Answer 32

Blocks Topoisomerase 1 = ssDNA break occurring Severe GI toxicity + 1A1 & 28 polymorphism Colon cancer

Question 33

Blemycin MOA + Toxicity

Answer 33

OH- radicals = DNA fragmentation | No significant bone marrow toxicity but some pulmonary fibrosis

Question 34

First-line drugs for tx of breast cancer in POSTmenopausal women

Answer 34

Anastrozole & Letrozole by being competitive nonsteroidal aromatase inhibitors

Question 35

Exemestane is a

Answer 35

STEROIDAL IRREVERSIBLE inhibitor of aromatase

Question 36

Trastuzumab MOA + toxicity

Answer 36

HER2 receptors | weakening heart muscles + CHF