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12 Cards in this Set

  • Front
  • Back
  • 3rd side (hint)
what's the point of using combination chemotherapy?
- avoid too much damage to any individual organ, avoid overlapping toxicity
- alternative myelosuppressive w/ non-suppressive drugs
-avoid resistance
which agents are not myelosuppressive?
-bleomycin, L asparaginase, and hormonal agents that can be used
1. especially GI toxic?
2. especially toxic to hair follicles?
3. especially toxic to reproductive
1. fluorouracil, bleomycin, methotrexate (oral, intestinal ulceration via mucosal damage, diarrhea; nausea via stimulation of chemoreceptor trigger zone aka vomit center stimulation)
2. cyclophosphamide, doxorubicin, vincristine, methotrexate, dactinomycin, paclitaxel
3. alkylating agents (irregular periods, premature menopause, infertility in men)

all antineoplastics are teratogenic
organ specific toxicity:
1. cardiac?
2. pulmonary?
3. nervous system?
4. renal
5. liver
6. local irritants
7. carcinogenic
1.
- doxorubicin, daunorubicin (dexrazoxane, cardioprotective agent)
- cyclophosphamide (subendocardial hemorrhage)

2.
-bleomycin, busulfan (pulm interstitial fibrosis)
- melphalan, carmustine (injury)

3.
- cisplatin, hexamethylamine, paclitaxel (periph neuropathies)
- procarbazine, L-asparaginase, ifosfamide (disorientation, somnolence)
- cytarabine (cerebral damage)

4.
- cisplatin, streptozocin, methotrexate (high dose) (tubular damage)(+amisfostine, glutathione b/c scavange free radicals)
- cyclophosphamide, ifosfamide (hemorrhagic cystitis of bladder)

5. methotrexate, L-asparaginase, mercaptopurine, azathioprine

6. can't be injected or caution with IV: anthracyclines, vinca alkaloids, mechlorethamine, dactinomycine, mithramycin, mitomycin C, nitrosureas

7. alkylating agent, anthracyclines, procarbazine
alkylating agents.
cell cycle dependent?
action?
resistance?
-covalent binding to nucleophilic groups causes cross-linking of DNA strands; transfers alkyl group to impt macromolecules
- nucleophilic groups like phosphate, amino, sulfhydryl, hydroxyl, carboxyl, imidazole
- unpaired DNA more susceptible obviously, so late G1 or S, but these single strand alkylations are more easily repaired so trade off
- cell cycle independent
- more cytotoxic (effective) in rapidly proliferating cells
-traps cells in S aka premitotic phase; can't progress to G2

resistance:
1. up dna repair
2. decreased cell permeability
3. other nucleophilic substances made that compete for alkylation: glutathione conjugates and inactivates alkylating agent; or up glutathion S transferase which catalyzes that conjugation
alkylating agents:
toxicity?
-more toxic in rapidly proliferating cells:
- immunosuppressive
- epithelial tissues
- vesicant action (skin, eyes, respiratory tract)
- reproductive tissues (amenorrhea, messed up spermatogenesis)
- CNS (nausea, vomit, convulsions, paralysis, cholinomimetic)
- Bladder fibrosis (cyclphosphamide)
procarbazine:
category?
mech?
resistance?
toxicity?
- alkylating agent
- mech: inhibits DNA, RNA, protein synth via DNA methylation and free radical formation which induce ss DNA breaks

resistance: repair of methylated groups, NOT CROSS RESISTANT WITH OTHER AGENTS

toxicity: carcinogenic, MAO inhib, myelosuppression, GI, neuro, dermatological
what's significant about nitrosureas agents as a subcategory of alkylating agents?
- non cross resistant with other alkylating agents
- require biotransformation via nonenzymatic decomposition
- highly lipid soluble (blood-brain)
cisplatin/carboplatin
category?
mech?
resistance?
toxicity?
difference b/t the two?
-alkylating agents
mech: react w/ nucleophiles, cross linkage of platinum w/ guanines and sulfhydryls; stop DNA synth; not cell cycle specific

resistance: dna repair
(oxaloplatin not cross resistant w/ these two agents)

toxicity:
-cisplatin: renal, ear, periph neurop.; saline IV hydration MUST for kidney protection
carboplatin: less renal toxicity; myelosuppression (which limits its dosing)

ways to decrease toxicity?
1. HYDRATION for cisplatin
2. amifostine for cisplating(when dephosphorylated protects against cisplatin metabolites, and normal tissues have more alkaline phosphatase for dephosphorylation so :) )
3. glutathione for cisplatin (protects against nephrotoxicity)
cyclophosphamide:
category?
toxicity?
alkylating agent
- nausea/vomit, myelosupp
- hemorrhagic cystitis
- orally for 10 days or IV single dose
carmustine:
category?
toxicity?
alkylating agent
- nausea/vomit; leukopenia, thrombocytopenia, rare hepatitis w/ prolonged use
- IV every 6 weeks
meclorethamine:
category?
toxicity?
alkylating agent
- nausea/vomit, meylosupp
- IV single or divided doses