B/32. Cancer Chemotherapy I (antimetabolites)

Question 1

Drugs need to know in this topic

Answer 1

Fluorouracil (5-FU)
Methotrexate
6-Mercaptopurine
Cytarabine
Capecitabine
Pemetrexed

Question 2

Antimetabolites

Answer 2

Interfere with the availability of normal purine or pyrimidine nucleotide precursors
Inhibiting synthesis or competing with them in DNA or RNA synthesis
Cytotoxic effects are in S-phase

Question 3

Fluorouracil (5-FU)

Answer 3

CCS
Pyrimidine antimetabolite
Bioactivated to inhibit thymidylate synthetase
Effect enhanced with the addition of folinic acid(Leucovorin), reduced form of folic acid

Solid tumor(Breast, Gastric, Ovarian, Head and neck, colon, bladder cancer, Hepatocellular carcinoma)
Topical to basal cell carcinoma

Myelosuppresion, diarrhea, mucositis, cardiotox
Megaloblastic anemia
Hand foot syndrome

Question 4

Methotrexate

Answer 4

CCS
Folate antimetabolite
Inhibits dihydrofolate reductase(DHFR)
DHF cannot be tranversed into THF, resulting in decreased synthesis of DNA, RNA, proteins

Oral/parenteral

1. Solid tumor (Breast, Head and neck, Bladder cancer)
2. Lymphoma (Primary CNS lymphoma, Non-Hodgkin’s lymphoma)
3. Germ cell tumor (Choriocarcinoma)
4. Ectopic pregancy management
5. Autoimmune/inflammatory disorders (psoriasis, IBD, SLE)

Myelosuppression rescued by leucovorin
folate deficiency, Toxic effects to skin, GI mucosa(mucositis)
Megaloblastic anemia
Hepatotoxicity (microvesicolar fatty change)
Pulmonary fibrosis
CI in pregancy (neural tube, congenital heart defect)

Question 5

6-Mercaptopurine

Answer 5

CCS
Purine antimetabolite
Bioactivated by HGPR transferase to inhibit several enzymes involved in purine metabolism

ALL
CML

Myelosuppression (Pancytopenia)
Hepatotoxicity
Immunosuppression
Teratogenic
Increased risk for infection
Megaloblastic anemia
Acute pancreatitis

Allopurinol inhibits 6-MP metabolism->elevated levels with increased risk for toxicity

Question 6

Cytarabine (Ara-C)

Answer 6

CCS
Cytosin arabinoside
Pyrimidine antimetabolite
Bioactivated to inhibit DNA polymerase

AML
Non-Hodgkin’s lymphoma

Myelosuppresion, megaloblast anemia

Question 7

Capecitabine

Answer 7

CCS
Bioactivated to 5-FU
Oral

Breast cancer(metastatic, resistant to 1st line drugs)
Colon cancer

Myelosuppresion
Nausea, voming
CI in pregranancy and lactation

Question 8

Pemetrexed

Answer 8

CCS
Folate antibetabolite

Non-small cell lung carcinoma
Mesothelioma

Myelosuppression
Nausea, vomiting