Chemo agents Flashcards
Bleomycin
Antitumor antibiotic
Induces free radicals formation
G2
Testicular Vulvar Cervical ca
Hodgkins lymphoma
Pulmonary fibrosis
Skin hyperpigmentation: flagellated erythema
Myelosuppression
Dactinomycin
Actinomycin D
Antitumor antibiotic
Intercalates into DNA —> breaks
Inhibits RNA synthesis
Wilms Ewing Rhabdomyosacroma
Myelosuppression
Doxorubicin
Daunorubicin
Antitumor antibiotic
Intercalates into DNA
Free radical formation (by binding iron)
Blocks topoisomerase 2 (knicks in dna rep)
Leukemias Lymphomas Solid tumors
Cardiotoxicity (dilated myopathy, systolic)
Alopecia
Myelosuppression
Use Dexrazoxane iron chelator to prevent cardiac toxicity
Tumor cells have developed P glycoprotein: ATP dependent efflux pumps bs anthacyclins
Azathioprine
—->
6 Mercaptopurine
Antimetabolite
Purine analog: inhibits de novo purine synthesis
Activation by HGPRT (AZA —> 6MP)
Metabolized by Xanthine Oxidase: toxicity with allopurinol and febuxostat
Prevent organ rejection, RA, IBD, SLE
To wean patients off steroids
Treat steroid refractory chronic disease
GI: hepatitis, cholestasis, pancreatitis
Myelosuppression
Cladribine
Antimetabolite
Purine analog
Inhibits DNA polymerase and induces strand breaks (interferes with DNA synth but cell cycle non specific)
Hairy cell leukemia
Resistant to ADA degradation
Myelosuppression
Nephrotoxic
Neurotoxic
Cyrtarabine
Arabinofuranosyl cytidine
Antimetabolite
Pyrimidine - C - analog
DNA chain termination and DNA polymerase inhibition: decreased DNA synthesis/ S phase
Leukemias Lymphomas
Myelosuppression
Megaloblastic anemia
Pancytopenia
Neurotoxic
5 fluorouracil
Capecitabine (prodrug)
Antimetabolite
Pyrimidine - U - analog
Bioactivated to 5 FdUMP which complexes with thymidiyate synthase and folic acid
Inhibition of thymidylate synthase: decreased dTMP and decreased DNA synthesis/ S phase
Colon ca Pancreatic ca Basal cell ca
Leucovorin enhances effect
Myelosuppression Palmar-plantar erythrodysesthesia CNS Coronary vasospasm Mucositis
Methotrexate
Antimetabolite
Folic acid analog
Competitively inhibits dihydrofolate reductase
Decreased dTMP and decreased DNA synthesis/ S phase and de novo thymidine synthesis
Leukemias Lymphomas ChorioCA Sarcomas
Ectopic pregnancy Medical abortion
RA Psoriasis IBD Vasculitis
Reversible with leucovorin (THF)
Accumulation of DHF metabolites (DHF polyglutamate)
And MTX undergoes polyglutamation inside the cell for future use
Myelosuppression Hepatotoxic Mucositis Nephrotoxic Folic acid deficiency Pulmonary fibrosis
Busulfan
Alkylating agent
Cross links DNA
Ablate BM before transplant
Myelosuppression
Pulmonary fibrosis
Hyperpigmentation
Cyclophosphamide
Ifosfamide
Alkylating agent = N mustard
Cross links DNA at Guanine
Alkylating agent
Requires liver bioactivation (cyp4502B)
Solid tumors Leukemias Lymphomas
RA SLE Granulomatosis with polyangiitis
Myelosuppression
Nephrotoxicity and Fanconi
SIADH
Hemorrhagic cystitis and Bladder cancer ( metabolized in kidneys to Acrolein which is toxic to uroepithelial cells : death and necrosis)
Prevented with mesna (sulfhydryl / thiol group binds toxic metabolites) and hydration
Nitrosoureas
carmustine lomustine
Alkylating ageny
Cross link DNA
Require liver bioactivation
Cross BBB- lipid soluble
Brain tumors
CNS toxicity
Myelosuppression
Procarbazine
Alkylating agent
Mechanism??? cell cycle non specific
Hodgkin’s and Brain tumors
BM suppression
Pulmonary toxicity
Disulfiram like reaction
Paclitaxel
Taxanes
Microtubule inhibitors
-Taxes stabilize society-
Hyperstabilize polymerized microtubules in M phase
Mitotic spindle cant break down
Anaphase cant happen
Ovarian and Breast CA
Myelosuppression
Neuropathy
Hypersensitivity
Vincristine
Vinblastine
Microtubule inhibitors
Vinka alkaloids
Bind beta tubulin and inhibit polymerization into microtubules
Prevent mitotic spinde formation (M phase)
Solid tumors
Leukemias and Lymphomas
Neuropathy: areflexia
Constipation: paralytic ileus
BM suppression
Cisplatin
Carboplatin
Oxaliplatin
Cross link DNA at G N7
Testicular, bladder, ovarian, GI, lung
Nephrotoxic (Fanconi) -
Amifostine (free radical scavenger) +NSS
Peripheral neuropathy
Ototoxicity
