Onc Drugs (A) Flashcards
Mechanism:
Azathioprine
6-mercaptopurine
Purine (thiol) analog → decrease de novo purine synthesis
Activated by HGPRT
Azthioprine is metabolized into 6-MP
Clinical use:
Azathioprine
6-mercaptopurine
- Preventing organ rejection
- RA
- IBD
- SLE
- Used to wean patients off steroids in chronic disease
- Treat steroid-refractory chronic disease
Adverse effects:
Azathioprine
6-mercaptopurine
- Myelosuppression
- GI disturbances - abd pain
- Hepatotoxicity - jaundice
- Increased toxicity with allopurinol or febuxostat
Mechanism: Cladribine
Purine analog → multiple mechanisms:
- Inhibition of DNA polymerase
- DNA strand breaks
Clinical use: Cladribine
- Hairy cell leukemia
Adverse effects: Cladribine
- Myelosuppression
- Nephrotoxicity
- Neurotoxicity
Mechanism: Cytarabine
Pyrimidine analog → inhibition of DNA polymerase
Clinical use: Cytarabine
Leukemias (AML)
Lymphomas
Adverse effects: Cytarabine
- Myelosuppression + megaloblastic anemia
- Pancytopenia
Mechanism: 5-fluorouracil
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
Clinical use: 5-fluorouracil
- Colon cancer
- Pancreatic cancer
- Basal cell carcinoma (topical)
Effects enhanced with addition of leucovorin
Adverse effects: 5-fluorouracil
- Myelosuppression
- Palmar-plantar erythrodysesthesia (hand-foot syndrome)
Mechanism: Methotrexate
Folic acid analog that competitively inhibits dihydrofolate reductase → decreased dTMP → decreased DNA synthesis
Clinical use: Methotrexate
Neoplastic
- Leukemias (ALL)
- Lymphomas
- Choriocarcinoma
- Sarcomas
Non-neoplastic
- Ectopic pregnancy
- Medical abortion (with misoprostol)
- RA
- Psorasis
- IBD
- Vasculitis
Adverse effects: Methotrexate
- Myelosuppression (reversible with leucovorin)
- Hepatotoxicity
- Mucositis (e.g., mouth ulcers)
- Pulmonary fibrosis
Mechanism: Capecitabine
Prodrug with similar acitvity as 5-FU