Chemotherapy Flashcards
Busulfan
Alkylating agent–> cross links DNA leading to strand breaks and abnormal base pairing
Independent of cell cycle (but most effective in G1 and S)
USE: ablate bone marrow prior to bone marrow transplant
Adverse Effects: Pulmonary Fibrosis, hyperpigmentation
Cyclophosphamide, ifosfamide
Nitrogen mustard Alkylating agents–> cross links DNA at guanine leading to strand breaks and abnormal base pairing. requires bioactivation at liver
Independent of cell cycle (but most effective in G1 and S)
USE: solid tumors, lymphoma, leukemia (and breast and ovarian cancer according to lecture)
Adverse effects: myelosuppression, SIADH, hemorrhagic cystitis - all can be prevented with adequate hydration or mesna (thiol group binds toxic metabolites)
Nitrosureas - carmustin
Alkylating agent–> requires bioactivation, then crosses BBB into CNS–>cross links DNA leading to strand breaks and abnormal base pairing
Independent of cell cycle (but most effective in G1 and S)
USE: brian tumors –> glioblastoma multiforme
Adverse effects: CNS toxicity - convulsions, dizziness, ataxia
“Carmustin is a NitroSuria –> CNS”
Procarbazine
Cell cycle phase nonspecific-Alkylating agent–> mechanism unclear
USE: hodgkins lymphoma, braintumors
Adverse effects: bone marrow suppression, pulmonary toxicity, leukemia (**high risk of secondary malignancy)
Also acts as MAOI - CI with alcohol, sympathomimetics, TCAs, anti-histamines, and CNS depressants
“PRO” extra cancer
Cisplatin, carboplatin
Platinum compouds. act like alkylating agents - cross link DNA
USE: bladder, testicular, ovary, and lung carinomas (NSCLC, SCLC)
Adverse effects: nephrotoxicity, ototoxicity, peripheral neuropathy, highly emetogenic
amifostine (free radical scavenger) and saline diuresis cant prevent nephrotoxicity.
Carboplatin is less toxic
Oxaliplatin
Platinum compouds. act like alkylating agents - cross link DNA. effective in cells with MMR
USE: colorectal cancer
Toxicity: neurotoxicity - includes reversible peripheral sensory neuropathy that is triggered by the cold
Methotrexate
Premetrexed
Antimetabolite
folic acid analog - competitively inhibits DHFR which decreases dTMP and thus decreases DNA synthesis
USE: all leukemias, lymphomas,choriocarcinoma, sarcomas
Non-neoplastic use: ectopic pregnancy, medical abortion, RA, psoriasis, IBD, vasculitis
Adverse effects:
-myelosuppresion (reversible with leucovorin
-hepatotoxicity
-folate deficiency -teratogenic
Cellular resitance due to decreased formation of cytotoxic MTX polyglutamates
Note: premtrexed - blocks TS, used fro NSCLC
5-fluorouracil
Antimetabolite
Pyrimidine analog bioactivated to 5-FuDUMP. complexes with TS (thymidylate synthase) and folic acid which inhibits dTMP and finally DNA synthesis–> inactivates pyrimidine synthesis
USE: colon cancer, pancreatic caner, actinic keratosis, basal cell carcinoma
Adverse effects: palmar-plantar erythrodysesthesia (Hand-foot syndrome)
CI: DPD deficiency
Potentiated by leucovorin
Capecitabine
pro drug of 5-FU with similar activity
Adverse effects: palmar-plantar erythrodysesthesia (Hand-foot syndrome)
NOT notorious for alopecia
Cytarabine, gemcitabine
Antimetabolite - pyrimidine analog that results in chain termination. Inhibits DNApol at high concentrations
USE: hematologic malignancy only - luekemias, lymphomas
TOX: myelosuppression with megaloblastic anemia
CYT causes panCYTopenia
NOTE: gemcitabine - adverse effect of HUS
Azathioprine, 6-mercaptopurine
Antimetabolite - purine analog
Activated by HGPRT to then decrease purine de novo synthesis
USES: preventing organ rejection, RA, IBD, SLE (to wean pts off steroids in chronic disease or to treat steroid refractory disease)
*Deactivated by xanthine oxidase, so allopurinol can result in toxicity (and febuxostat)
*Azathiopurine is metabolized into 6-mercaptopurine
CI TPMT deficiency
Cladribine
Antimetabolie - purine analog
results in DNA pol inhibition and DNA strand breaks
USE: Hairy cell leukemia
TOX: neuro + nephrotoxicity
Paclitaxel, Docetaxel
Microtubule inhibitor - hyperstabilize microtubule in M phase so mitotic spindle cant break down (anaphase cant occur)
USE: breast and ovarian cancer
TOX:
“TAXes STABILIZE society”
Vincristine, Vinblastine
Microtubule inhibitor: vince alkaloids - bind Beta-tubulin and prevent microtubule polymerization and thus prevent mitotic spindle formation (M-phase arrest)
USE: solid tumors, leukemias, hodgkin (vinblast) and non-hodgkins (vincrist)
TOX:
vincrist: peripheral neuropathy, ANS dysfunciton, SIADH “crisp nerves”
Vinblast: potent blistering agent and bone marrow suppression “blasts the bones and skin”
Topotecan
Inhibits topo1–> DNAunwinding and replication prevented
USE: ovarian cancer, SCLC
TOX: severe myelosuppression and diarrhea**
Etoposide, teniposide
Inhibits topo2 –> DNA degredation
S phase arrest
USE: solid tumors- specifically testicular and SCLC,
“Someone by my SIDE -tope TWO)
irinotecan
Prodrug
Inhibits topo1–> DNA unwinding and replication prevented
G2 and S phase arrest
USE: colorectal cancer
Doxorubicin, danorubicin
Antitumor antibiotic
Generate free radicals, intercalate in DNA–>break DNA–>decreased repilcation
Also interferes with topo2
USE: Solid tumors, leukemia, lymphoma
TOX: does dependent cardiomyopathy - prevented with iron chelator -Dexrazoxane
“ruby is radical”
Mitoxantrone
Antitumor antibiotic
Generate free radicals, intercalate in DNA–>break DNA–>decreased repilcation
TOX: blue sclera and fingernails
mitomycin C
Anti-tumor antibiotic - corss links DNA and effects all phases of cell cycle
Acts on tumors in hypoxic environments
Tox: HUS
Bleomycin
Anti-tumor antibiotic - Induces free radical formation which breaks DNA (SSB and DSB) - G2 phase arrest
USE: Testicular cancer and hodgkins lymphoma
TOX: Pulmonary Fibrosis, hyperpigmentation
Dactinomycin (actinomycin D)
Antitumor antibiotic -intercalates into DNA preventing RNA synthesis
USE: WIlms tumor, Ewing sarcoma, rhabdomyosarcoma, Childhood tumors
Vemurafenib
Small molecule inhibitor of BRAF oncogene + melanoma
“VEmuRAF-enib = V600E mutated bRAF inhibition”
