(8) Antineoplastics: DNA & Cell... (2.1-2.5)

Question 1

MOA: Cyclophosphamide

Answer 1

Cytotoxic alkylating agent

Question 2

Suffix: Nitrosoureas

Answer 2

“-mustine”

Question 3

MOA: Busulfan

Answer 3

Cytotoxic alkylating agent

Question 4

MOA: Nitrosoureas

Answer 4

Cytotoxic alkylating agent

Question 5

How is Cyclophosphamide activated?

Answer 5

Hepatic CYP450 system

Question 6

Indication - Non-neoplastic: Cyclophosphamide

Answer 6

Immunosuppressive agent

(Note: According to Golan, suppresses B-cell response, but actually potentiates T-cell response)

Question 7

Adverse Effects (5) : Cyclophosphamide

Answer 7

(1) Myelosuppression
(2) Hemorrhagic cystitis
(3) Bladder cancer (transitional cell)
(4) SIADH
(5) Infertility

Question 8

How can you prevent hemorrhagic cystitis when administering Cyclophosphamide?

Answer 8

Hydration + MESNA

Question 9

Indication: Busulfan

Answer 9

Bone marrow depletion

(Also CML)

Question 10

Adverse Effects (2) : Busulfan

Answer 10

(1) Pulmonary fibrosis
(2) “Busulfan tan”
* (Severe myelosuppression, blurs the line between effect and adverse effect)*

Question 11

Which Nitrosourea does not have the “-mustine” suffix?

Answer 11

Streptozocin

Question 12

Which class of alkylating agents can cross the blood-brain barrier?

Answer 12

Nitrosoureas

(Require O-6 alkylation before they’re cytotoxic)

Question 13

Adverse Effect (1) : Nitrosoureas

Answer 13

Neurotoxicity

Question 14

Cell Cycle Specificity: Alkylating agents

Answer 14

Cell cycle non-specific

(Includes platinum analogs)

Question 15

What type of cancers does Cyclophosphamide treat?

Answer 15

(1) Hematologic
(2) Solid malignancies

Question 16

MOA: Platinum analogs

Answer 16

Cross-link DNA

Question 17

Adverse Effects (5) : “-platins”

Answer 17

(1) Ototoxicity
(2) Peripheral neuropathy
(3) Nephrotoxicity
(4) Acute tubular necrosis
(5) Myelosuppression
* (Oto-/Nephrotoxicity: Cisplatin > Carboplatin >>> Oxaliplatin)*

Question 18

Name 2 ways to prevent Cisplatin-induced nephrotoxicity

Answer 18

(1) Co-administer Amifostine
(2) IV Saline diuresis

Question 19

MOA: Amifostine

Answer 19

Neutralizes free-radicals (in kidney)

Question 20

What type of cancers do “-platins” treat?

Answer 20

Various solid malignancies

(Most notably BEP therapy for testicular cancer)

Question 21

MOA: Bleomycin

Answer 21

Binds DNA then produces free radical ⇒ Cleaves DNA

Question 22

Cell Cycle Specificity: Bleomycin

Answer 22

G2

Question 23

Adverse Effects (4) : Bleomycin

Answer 23

(1) Pulmonary toxicity
(2) Skin toxicity
(3) Stomatitis/Mucositis
(4) Alopecia
* (Bleomycin is activated by oxygen ∴ highly oxygenated environment of lung predisposes to collateral damage)*

Question 24

Suffix: Anthracyclines

Answer 24

“-rubicin”

Question 25

**MOA**: Anthracyclines

Answer 25

(1) Produce free radicals (2) Intercalate DNA

Question 26

**Adverse Effects** (4) : Anthracyclines

Answer 26

(1) Dilated cardiomyopathy (2) Myelosuppression (3) Stomatitis/Mucositis (4) Alopecia

Question 27

What drug can prevent Anthracycline-induced cardiotoxicity?

Answer 27

Dexrazoxane

Question 28

**MOA**: Dexrazoxane

Answer 28

Iron chelator *(Scavenging iron prevents the Fenton reaction from generating free radicals)*

Question 29

**MOA**: Actinomycin D

Answer 29

Intercalates DNA

Question 30

What type of cancers does actinomycin D treat?

Answer 30

Numerous pediatric malignancies *(i.e., Wilms tumor, Ewing sarcoma, rhabdomyosarcoma)*

Question 31

What type of cancers does Bleomycin treat?

Answer 31

(1) Hematologic (2) Solid malignancies * (Same for anthracyclines)*

Question 32

Suffix: Topoisomerase II Inhibitors

Answer 32

"-poside"

Question 33

**Suffix**: Topoisomerase I Inhibitors

Answer 33

"-tecan"

Question 34

What is the function of Topoisomerase II?

Answer 34

Induces dsDNA nicks ⇒ Relieves supercoiling stress *(Topoisomerase I ⇒ ssDNA nicks)*

Question 35

**MOA**: Etoposide

Answer 35

Inhibits religation of **ds**DNA breaks created by Topoisomerase II

Question 36

**Cell Cycle Specificity**: Topoisomerase inhibitors

Answer 36

(1) S (2) G2

Question 37

**Adverse Effects** (3) : Topoisomerase II inhibitors

Answer 37

(1) Myelosuppression (2) ⇒ Immunosuppression (3) Alopecia

Question 38

**MOA**: Irinotecan

Answer 38

Inhibits Topoisomerase I

Question 39

Are Topoisomerase I or II inhibitors associated with severe, potentially life-threatening, diarrhea?

Answer 39

Topoisomerase I inhibitors

Question 40

What type of cancers do "-posides" treat?

Answer 40

(1) Hematologic (2) Solid malignancies

Question 41

What type of cancers does Topotecan treat?

Answer 41

(1) Ovarian cancer (2) Small cell lung cancer

Question 42

What type of cancers does Irinotecan treat?

Answer 42

Colon cancer

Question 43

**MOA**: Vinca alkaloids

Answer 43

Inhibits microtubule assembly *(∝ Inhibiting kinesin ∝ Colchicine, which all have the 'kuh' sound)*

Question 44

**Cell Cycle Specificity**: Microtubule inhibitors

Answer 44

M phase

Question 45

**Adverse Effects** (4) : Vinca alkaloids & Taxanes

Answer 45

(1) Peripheral neuropathy (2) Paralytic ileus/Constipation (3) Alopecia (4) Myelosuppression

Question 46

Which Vinca alkaloid is known for significant _myelosuppression_?

Answer 46

Vinblastine *("Vinblastine blasts your bone eye marrow")*

Question 47

**MOA**: Taxanes

Answer 47

Inhibit microtubule **_degradation_** *(∝ Inhibiting dynein ∝ C. Diff exotoxins B's effect on actin)*

Question 48

What type of cancers do Vinca alkaloids treat?

Answer 48

(1) Hematologic (2) Solid malignancies