Oncology Flashcards
Azathioprine
6-mercaptopurine
Inhibit S phase in cell cycle
MOA:
Purine analogs —> dec. de novo purine synthesis
Activated by HGPRT
Azathioprine is metabolized into 6-MP
Use: Preventing organ rejection Rheumatoid arthritis IBD SLE Used to wean ptns off steroids in chronic disease and to treat steroid refractory chronic disease.
Adv. effects: Myelosuppression GI Liver Increased toxicity with allopurinol or febuxostat
Cladribine
Inhibit S phase in cell cycle
MOA:
Purine analong —> mult. mechanisms (inhibitin of DNA pol., DNA strand breaks)
Use: Hairy cell leukemia
Adv. effects:
Myelosuppression
Nephrotoxicity
Neurotoxicity
Cytarabine
Inhibit S phase in cell cycle
MOA: Pyrimidine analog —> inhibition of DNA polymerase
Use:
Leukemias (AML)
Lymphomas
Adv. effects:
Myelosuppression w/ megaloblastic anemia
“CYTarabine causes panCYTopenia”
5-fluorouracil
Inhibit S phase in cell cycle
MOA:
Pyrimidine analog bioactivated to 5-FdUMP
5-FdUMP covalently complexes folic acid
Complex inhibits thymidylate synthase —> dec. dTMP —> dec. DNA synthesis
Use:
Colon cancer
Pancreatic cancer
Basal cell carcinoma (topical)
Effects enhanced with the addition of leucovorin
Adv. effects:
Myelosuppresion - worsened with add. of leucovorin (folinic acid)
Methotrexate
Inhibit S phase in cell cycle
MOA:
Folic acid analog that competitively inhibits diydrofolate reductase –> dec. dTMP —> dec. DNA synthesis
Use:
Cancers - leukemias (ALL), lymphomas, choriocarcinoma, sarcomas
Non neoplastic - ectopic pregnancy, medical abortion (w/misoprostol), rheumatoid arthritis, psoriasis, IBD, vasculitis
Adv. effects: Myelosuppression - reversible with leucovorin "rescue" Hepatotoxicity Mucositis (mouth ulcers) Pulmonary fibrosis
Bleomycin
Inhibits G2 phase of cell cycle
MOA:
Induces free radical formation –> breaks in DNA strands
Use:
Testicular cancer
Hodgkin lymphoma
Adv. effects:
Pulmonary fibrosis
Skin hyperpigmentation
Minimal myelosuppression
Dactinomycin
MOA: Intercalates in DNA
Use:
Wilms tumor
Ewing sarcoma
Rhabdomyosarcoma
Used for childhood tumors ("children ACT out")
Adv. effects:
Myelosuppression
Doxorubicin, Daunorubicin
MOA:
Generate free radicals
Intercalate in DNA –> breaks in DNA –> dec. replication
Use:
Solid tumors
Leukemias
Lymphomas
Adv. effects:
Cardiotoxicity* (dilated cardiomyopathy)
Myelosuppression
Alopecia
Dexrazoxane - iron chelating agent; used to prevent cardiotoxicity
Busulfan
MOA: Cross links DNA
Use:
CML
Used to ablate patient’s bone marrow before bone marrow transplantation
Adverse effects:
Severe myelosuppression
Pulmonary fibrosis
Hyperpigmentation
Cyclophosphamide, Ifosfamide
MOA:
Cross-link DNA at guanine N-7
Require bioactivation by liver
Use:
Solid tumors
Leukemia
Lymphomas
Adv. effects:
Myelosuppression
Hemorrhagic cystitis (prevented w/ mesna or N-acetylcysteine)
Nitrosoureas
Carmustine, Lomustine, Semustine, Streptozocin
MOA:
Require bioactivation
Cross blood-brain barrier —> CNS
Cross link DNA
Use: Brain tumors (including glioblastoma multiforme)
Adv. effects: CNS toxicity (convulsions, dizziness, ataxia)
Paclitaxel
MOA:
Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur)
Use:
Ovarian & breast carcinomas
Adv. effects:
Myelosuppression
Neuropathy
Hypersensitivity
Vincristine
Vinblastine
MOA:
Vinca alkaloids that bind B-tubulin and inhibit its polymerization into microtubules –> prevent mitotic spindle formation (M-phase arrest)
Use: Solid tumors Leukemias Hodgkin lymphoma (vinblastine) Non-Hodgkin lymphoma (vincristine)
Adv. effects:
Vincristine - neurotoxicity, constipation
Cisplatin
Carboplatin
MOA: Cross-link DNA
Use:
Testicular, bladder, ovary and lung carcinomas
Adv. effects:
Nephrotoxicity, peripheral neuropathy, ototoxicity
Prevent nephrotoxicity w/ amifostine (free radical scavenger) and chloride (saline) diuresis
Etoposide, Teniposide
MOA:
ETOPOside inhibits TOPOisomerase II –> Increases DNA degradation
Use:
Solid tumors (testicular & small cell lung cancer)
Leukemias
Lymphomas
Adv. effects:
Myelosuppression
Alopecia
Irinotecan, Topotecan
MOA:
Inhibit topoisomerase I and prevent DNA unwinding and replication.
Use: Colon cancer (irinotecan) Ovarian and small cell lung cancers (topotecan)
Adv. effects:
Severe myelosuppression
Diarrhea
Hydroxyurea
MOA:
Inhibits ribonucleotide reductase –> dec. DNA synthesis (S-phase specific)
Use:
Melanoma
CML
Sickle cell disease (increase HbF)
Adv. effects:
Severe myelosuppression
Prednisone, Prednisolone
MOA:
Bind intracytoplasmic steroid receptor
Alter gene transcription
Use:
CLL
non-Hodgkin lymphoma (part of combo regimen)
used as immunosuppressants (in autoimmmune diseases)
Adv. effects: Cushing-like symptoms Weight gain Central obesity Muscle breakdown Cataracts Acne Osteoporosis Hypertension Peptic ulcers Hyperglycemia Psychosis
Bevacizumab
MOA:
Monoclonal antibody against VEGF; inhibits angiogenesis
Use: Solid tumors (colorectal cancer, renal cell carcinoma)
Adv. effects:
Hemorrhage, blood clots, & impaired wound healing
Erlotinib
MOA: EGFR tyrosine kinase inhibitor
Use: Non-small cell lung carcinoma
Adv. effects: Rash
Cetuximab
MOA: Monoclonal antibody against EGFR
Use:
Stage IV colorectal cancer (wild type KRAS)
Head and neck cancer
Adv. effects:
Rash, elevated LFTs, diarrhea
Imatinib
MOA:
Tyrosine kinase inhibitor of BCR-ABL (in CML) and c-kit (in GI stromal tumors)
Use:
CML
GI stromal tumors
Adv. effects:
Fluid retention
Rituximab
MOA:
Monoclonal antibody against CD20 (found on most B-cell neoplasms)
Use: Non-Hodgkin lymphoma CLL ITP Rheumatoid arthritis
Tamoxifen, Raloxifene
MOA:
Selective estrogen receptor modulators - receptor antagonists in breast and agonists in bone
Block binding of estrogen to ER + cells
Use:
Breast cancer treatment (tamoxifen) & prevention
Prevent osteoporosis (Raloxifene)
Adv. effects:
Tamoxifen - partial agonist in endometrium (increases risk of endometrial cancer); hot flashes
Raloxifene - no increase in endometrial carcinoma bc it is an estrogen receptor antagonist in endometrial tissue.
Both increase risk of thromboembolic events (DVT, PE)
