| A | B |
|---|
| Cyclophosphamide – phase nonspecific Dynamics/Kinetics | (antitumor) by alkylation at guanine residues and acrolein |
| Cyclophosphamide- Dynamics/Kinetics | CYP2B > Aldophosphamide> to tumor cells where it cleaves spontaneously to phosphoramide mustard |
| Ifosfamide – phase nonspecific Dynamics/Kinetics | Analog of cyclophosphamide, also is activate by ring hydroxylation in liver |
| Mesna Dynamics/Kinetics | Redcd kidney to free thiol cpd > reacts with urotoxic metabolites (acrolein) |
| Vincristine – M phase specific Dynamics/Kinetics | Binds ?-tubulin inhibits ?/?polymerization w/o spindle arrest in metaphase |
| Filgrastim Dynamics/Kinetics | G-CSF – stimulates CFU-G to increase neutrophil production |
| Etoposide Dynamics/Kinetics | complex formed w/topoII and DNA prevents resealing; S and G2 phases |
| Dacarbazine- phase nonspecific Dynamics/Kinetics | metabolic activation in the liver - active form MTIC |
| Dacarbazine- phase nonspecific Dynamics/Kinetics | methylating agent inhibiting DNA, RNA and protein synthesis |
| Cisplatin Dynamics/Kinetics | Cl- replaced by H2O, yields cation that binds nucleophiles on DNA and proteins – cross links and breaks |
| Methotrexate – cell stage specific Dynamics/Kinetics | Inhibits DHFR as a folic acid analog, S phase, best with rapidly dividing cells |
| Bleomycin | accumulation of cells in G2 with chromosomal abnormalities |
| Bleomycin Dynamics/Kinetics | ROS damages deoxyribose of thymidylate; single and DSB in DNA, scission |
| Dactinomycin Dynamics/Kinetics | intercalcates between adjacent guanine-cytosine base; also causes single strand breaks |
| Doxorubicin ” Dynamics/Kinetics I | I.Intercalate with DNA (affecting transcription and replication) |
| Doxorubicin –Dynamics/Kinetics II | II. form a complex with topoII and DNA and inhibit relegation fo broken DNA à apoptosis |
| Doxorubicin –Dynamics/Kinetics III | III. Cause direct damage to DNA via oxygen radicals |
| Cyclophosphamide Toxicities | Hemorrhagic cysts with acrolein metabolite, myelosuppression, GI ulceration |
| Ifosfamide Toxicities | vs. cyclophosphamide causes worse platelet suppression, neurotoxicity, nephrotoxicity |
| Ifosfamide Toxicities | Severe urinary tract and CNS toxicity (without use of hydration and mesna) |
| Mesna Toxicities | N/V/D/ GI effects occasionally , bad taste in mouth is common occasional HA, fatigue, limb pain |
| Vincristine –Toxicities | Limited myelosuppression, neurotoxicity ( paresthesia DTR loss motor weakness), |
| Filgrastim Toxicities | skin reactions following subq, rare cutaneous necrotizing vasculitis ; |
| Filgrastim Toxicities | bone pain, mild to moderate splenomegaly with long term therapy |
| Etoposide Toxicities | Development of an acute nonlymphocytic leukemia with a chromosome 11 at 11q23 (MLL gene) |
| Dacarbazine- Toxicities | flu-like syndrome consisting of chills, fever, malaise, and myalgias |
| Cisplatin Toxicities | associated with development of AML usually 4 years or more after treatment |
| Cisplatin Toxicities | severe N/V (used often with antiemetic) Poor CNS penetration, nephrotoxicity, ototoxicity |
| Bleomycin Toxicities | Minimal myelo/immunosuprsn; unusual cutaneous effectsand pulmonary fibrosis |
| Dactinomycin – Toxicities | if given during chickenpox or herpeszoster, a fatal disease process can occur |
| Dactinomycin – Toxicities | Fever and fatigue common; severe myelosuppression |
| Red urine causes by drugs and metabolites common. –can use iron chelator to minimize cardiac toxicity | Doxorubicin –Toxicities |
| Doxorubicin –Toxicities | Dose related cardiomyopathy due to oxygen radical formation. |
| Cyclophosphamide –Therapeutics | Frequently combo w/ Methotrexate, Doxorubicin, and Fluorouracil; |
| Ifosfamide – Therapeutics | Widely used to treat pediatric and adult sarcomas |
| Mesna Therapeutics | Prophylactic tx for hemorrhagic cysts caused by cyclopphosphamide/ifosfamide |
| Vincristine –Therapeutics | CHOP regimen – cyclophosphamide, doxorubicin, prednisone (and vincristine) - IV |
| Filgrastim Therapeutics | With high dose chemotherapy, subcutaneous or IV injection |
| Etoposide Therapeutics | Oral/iv - **toxicity is increased in patients with decreased serum albumin ** |
| Dacarbazine- Therapeutics | IV administered |
| Cisplatin Therapeutics | IV administration; poor CNS penetration |
| Methotrexate –Therapeutics | nephrotoxicity and severe myelosuppression if drug is not excreted properly |
| Bleomycin Therapeutics | Parenterally , good combo drug because of little overlapping s/e |
| Dactinomycin –Therapeutics | IV |
| Doxorubicin – Therapeutics | Solid tumors. Usually given IV –CHOPS combo, |
| Cyclophosphamide – phase nonspecific | *Active p53 activity required for apoptosis of tumor cells ; |
| Cyclophosphamide – therapeutics | solid tumors and slow growing tumor choice, tx for bone sarcoma |
| Ifosfamide – phase nonspecific | Can administer with methylene blue to limit neurotoxicity |
| Vincristine – M phase specific resistance | Multidrug resistant tumor cells , ? tubulin mutations |
| Filgrastim | Produced in E.Coli, not glycosylated ( as in nature) and has extra N-terminal Met. |
| Etoposide resistance | Mutations of topo II, drug pumps, p53 = resistance, from extract of Mandrake |
| Dacarbazine- phase nonspecific | Resistance had been ascribed by removeal by AGT |
| Cisplatin | Aluminum inactivates, so impt in administration or mixture |
| Methotrexate – cell stage specific | High dose tx for osteosarcoma req coadmin of leucovorin to resupply folate to cells |
| Bleomycin | Fermentation products of Strep. Verticillus |
| Dactinomycin – “antibiotic” also called Actinomycin D | First iolsated from Streptomyces sp. |
| Doxorubicin – phase nonspecific – “antibiotic” | Derived from Strep. Peucetius . multidrug resistance is observed. |
