Onc Drugs (A)

Question 1

Mechanism:

Azathioprine

6-mercaptopurine

Answer 1

Purine (thiol) analog → decrease de novo purine synthesis

Activated by HGPRT

Azthioprine is metabolized into 6-MP

Question 2

Clinical use:

Azathioprine

6-mercaptopurine

Answer 2

1. Preventing organ rejection
2. RA
3. IBD
4. SLE
5. Used to wean patients off steroids in chronic disease
6. Treat steroid-refractory chronic disease

Question 3

Adverse effects:

Azathioprine

6-mercaptopurine

Answer 3

1. Myelosuppression
2. GI disturbances - abd pain
3. Hepatotoxicity - jaundice
4. Increased toxicity with allopurinol or febuxostat

Question 4

Mechanism: Cladribine

Answer 4

Purine analog → multiple mechanisms:

• Inhibition of DNA polymerase
• DNA strand breaks

Question 5

Clinical use: Cladribine

Answer 5

1. Hairy cell leukemia

Question 6

Adverse effects: Cladribine

Answer 6

1. Myelosuppression
2. Nephrotoxicity
3. Neurotoxicity

Question 7

Mechanism: Cytarabine

Answer 7

Pyrimidine analog → inhibition of DNA polymerase

Question 8

Clinical use: Cytarabine

Answer 8

Leukemias (AML)

Lymphomas

Question 9

Adverse effects: Cytarabine

Answer 9

1. Myelosuppression + megaloblastic anemia
2. Pancytopenia

Question 10

Mechanism: 5-fluorouracil

Answer 10

Pyrimidine analog bioactivated to 5-FdUMP, which covalently complexes with thymidylate synthase and folic acid

Complex inhibits thymidylate synthase → decreased dTMP → decreased DNA synthesis

Capecitabine is a prodrug with similar activity

Question 11

Clinical use: 5-fluorouracil

Answer 11

1. Colon cancer
2. Pancreatic cancer
3. Basal cell carcinoma (topical)

Effects enhanced with addition of leucovorin

Question 12

Adverse effects: 5-fluorouracil

Answer 12

1. Myelosuppression
2. Palmar-plantar erythrodysesthesia (hand-foot syndrome)

Question 13

Mechanism: Methotrexate

Answer 13

Folic acid analog that competitively inhibits dihydrofolate reductase → decreased dTMP → decreased DNA synthesis

Question 14

Clinical use: Methotrexate

Answer 14

Neoplastic

1. Leukemias (ALL)
2. Lymphomas
3. Choriocarcinoma
4. Sarcomas

Non-neoplastic

1. Ectopic pregnancy
2. Medical abortion (with misoprostol)
3. RA
4. Psorasis
5. IBD
6. Vasculitis

Question 15

Adverse effects: Methotrexate

Answer 15

1. Myelosuppression (reversible with leucovorin)
2. Hepatotoxicity
3. Mucositis (e.g., mouth ulcers)
4. Pulmonary fibrosis

Question 16

Mechanism: Capecitabine

Answer 16

Prodrug with similar acitvity as 5-FU

Question 17

Mechanism: Bleomycin

Answer 17

Induce free radical formation → breaks in DNA strands

Question 18

Clinical use: Bleomycin

Answer 18

Testicular cancer

Hodgkin lymphoma

Question 19

Adverse effects: Bleomycin

Answer 19

Pulmonary fibrosis

Skin hyperpigmentation

MINIMAL myelosuppression

Question 20

Mechanism: Dactinomycin (actinomycin D)

Answer 20

Intercalates in DNA

Question 21

Clinical use: Dactinomycin (actinomycin D)

Answer 21

Wilms tumor

Ewing sarcoma

Rhabdomyosarcoma

(childhood tumors)

Question 22

Adverse effects: Dactinomycin (actinomycin D)

Answer 22

Myelosuppression

Question 23

Mechanism:

Doxorubicin

Daunorubicin

Answer 23

Generate free radicals

Intercalate in DNA → breaks in DNA → decrease DNA replication

Question 24

Clinical use:

Doxorubicin

Daunorubicin

Answer 24

Solid tumors

Leukemias

Lymphomas

Question 25

Adverse effects: Doxorubicin Daunorubicin

Answer 25

Cardiotoxicity (dilated cardiomyopathy) - prevent with **dexrazoxane** Myelosuppression Alopecia

Question 26

\_\_\_ is used to prevent cardiotoxicity with doxorubicin

Answer 26

Dexrazoxane

Question 27

Mechanism: Busulfan

Answer 27

Cross-links DNA

Question 28

Clinical use: Busulfan

Answer 28

CML (mainstay treatment is Imatinib) **Ablate bone marrow** prior to bone marrow transplantation

Question 29

Adverse effects: Busulfan

Answer 29

Severe myelosuppression (almost all cases) **Pulmonary fibrosis** Hyperpigmentation

Question 30

Mechanism: Cyclophosphamide Ifosfamide

Answer 30

Nitrogen mustard **Cross-link DNA** at **guanine N-7** Require bioactivation by liver

Question 31

Clinical use: Cyclophosphamide Ifosfamide

Answer 31

Solid tumors Leukemia Lymphomas **Cyclophosphamide** * Granulomatosis with polyangiitis (Wegener's granulomatosis) * Microscopic polyangiitis

Question 32

Adverse effects: Cyclophosphamide Ifosfamide

Answer 32

Myelosuppression **Hemorrhagic cystitis** - preventied with **mesna** or ***N*-acetylcysteine** (bind toxic metabolites)

Question 33

Mechanism: Nitrosoureas ## Footnote **(-MUSTINE)**

Answer 33

Require bioactivation Cross BBB → CNS **Cross-link DNA**

Question 34

Clinical use: Nitrosoureas ## Footnote **(-MUSTINE)**

Answer 34

Brain tumors (including glioblastoma multiforme)

Question 35

Adverse effects: Nitrosoureas ## Footnote **(-MUSTINE)**

Answer 35

CNS toxicity → convulsion, dizziness, ataxia

Question 36

Mechanism: Paclitaxel Other **taxols**

Answer 36

**Hyperstabilize polyerized microtubules in** **M phase** → mitotic spindle cannot break down → anaphase cannot occur

Question 37

Clinical use: Paclitaxel Other **taxols**

Answer 37

Ovarian and breast carcinomas

Question 38

Adverse effects: Paclitaxel Other **taxols**

Answer 38

Myelosuppression Neuropathy Hypersensitivity

Question 39

Mechanism: Vinblastine Vincristine

Answer 39

Vinca alkaloids that bind **beta-tubulin** and inhibit its polymerization into microtubules → prevent mitotic spindle formation (M-phase arrest)

Question 40

Clinical use: Vinblastine Vincristine

Answer 40

Solid tumors Leukemias Vinblastine → HL Vincristine → NHL

Question 41

Adverse effects: Vincristine

Answer 41

Neurotoxicity → areflexia, peripheral neuritis Constipation (including paralytic ileus)