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| heaptic, immunosuppresive, hemmorrhagic cystits) |
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| what drugs have cardiac tox-2 |
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| doxorubicin, daunorubicin |
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| immunsuppresive tox of drugs-2 |
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| whcih drugs have the elast bone marrow suppression-4 |
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| cisplatin, bleomycin, vincristine, asparaginase |
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| alkylating agents were devloped to use as? |
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| alkylating agents react with electron rich/poor atoms and form _ bonds |
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alkylating groups are electrophillic/phobic?
so they interact with _ gorups. ex-2? |
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phillic (electron poor)
neucelophillic (e- rich)
N2, O2 |
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| highly reactive, pos. charged alkyl intermediates |
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| what are targets for alkylation?-4 |
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| amino, phosphate, sulfahydryl (SH), hydroxyl (OH) -(on DNa, prooteins, etc) |
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| alkylating are monofuncuitonal or bufunctional? |
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what are the main targets for alkylation?
what does this also msotly accoutn for? why? |
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DNA bases (moslty purines like guanine)
cytotoxicity; proteins and small molecules alkylating aren't harmful |
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| monofunctional alkyl agents react with _ DNA whcih invovles-2 |
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Definition
1 strand
strnad breaking, mutagenic alkylations |
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| bifunctional aklyl agents react wiht _; produces- |
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atom on each DNA strnad
cross link covalently links the strnads of the double helix |
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alkylating agents bind directly/indirectly to DNA?
therefor they are what category of anticancer med? |
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Definition
directly
non cell cycle specific |
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slide 9 has chemisty of the alky;lators:
1)acitvaiton
2) nucelophillic attack on azidrine ring by E-donor |
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Definition
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| outcomes of alkylating rxn-4 |
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Definition
template misread/mispaired
cross linking prevents strand unwinding
single strnad breaks-> inhibit DNA/RNA protein synth
double strnad breaks- considereed mutagenic |
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| look at slide 12 right before test, has the alkylating groups and medds in each* |
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| what are the preffered sites for DNA alkylation-4 |
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Definition
N7 guanine
N2 guanine
O6 guanine
04 thymine |
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what are the monofunctional agents-4
(these induce methylation, strnad breaks, mutations) |
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Definition
| dacarbazine, procarbazine, temozoloamide |
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what are the bifucntional agents-4
(these have alkylation, cross links, strnad breaks, mutations |
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Definition
| N2 mustards, cyclophosphamides, nitrosureas, melphalan |
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| indicaitons for mustargen-2 |
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| whais the probelm with mustargen |
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Definition
| extravasation ( use thiosulfate and ice packs) |
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which mustard gas is injeciton only?
which is the most reactive |
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| indications for melphalan-1 |
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| pallatative of multiple myeloma |
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| causes chrom abnormalites |
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| oral/IV; reduce dose with low BUN |
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| what is teh most widely used alkylating agent |
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| indications for cyclophosphamide-4 |
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Definition
| lymphomas, solid tumor: breast, ovarian, lung |
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| which drug cna be used to prevent trnasplantation rejection |
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Definition
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| clyclophosphamide can be used for non maliganant immune disease such as- and also to break _ of cancer antigens |
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Definition
RA
immunsuppressive actions |
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| cyclophosphamide counseling-2 |
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Definition
oral/injection
safe with bad renal fnct |
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| what are the prodrugs metab in the liver-2 |
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Definition
cyclophosphamide
ifophosamide
(phosphamide mystards) |
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| ask someone if needd to know enzymes for slide 18 |
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Definition
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what is the toxic metab for clyclophosphamide?
what is its side effect
acrolein cna metab into-
this causes-2 |
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Definition
acrolein
hemorrhagic cystitis
mercaptethansulfonate
suprpubic pain, heamturia |
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Definition
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Definition
chlorambucil
(has azidirne species) |
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| indicaitons for Leukeran-2 |
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Definition
| leukemias (DOC, CLL) and lymphomas |
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what is the least toxic nutrogen mustard compound?
so how often are blood counts? |
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| the counseling point with Leukeran-2 |
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use contraception (terotegni)
major bone suppression |
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| urinary bladder papillary carcinoma |
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| ethylenemine radical disruptin DNA-> chain scission |
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| blood counts 3 wks post cessation. high tox bone suppression |
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nitrosureas has delayed/fast hematopoeitc tox? when is the nadir?
why? |
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delayed
5-6 wks post admin
damage early hematopetic precursor |
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what drugs are a good choice for brain tumors?
why? |
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Definition
nitrosureas
highly lipophillic to cross BBB |
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| what are the nitrosureas-4 |
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Definition
| Nimustine, semustine, Lomustine, carmustine |
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| DOC pallitative chronic myelogenous leukemia (CML) |
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severe mylosupression
use w/ allopurinol since can cause hyperuricemia |
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| which med is used for bone marrow ablation prior to trnasplant? |
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Definition
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| which drug has a remission rate of 90% after 1 dose |
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Definition
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| mitomycin contains these groups that have cytotxicity- |
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Definition
quinone (free radical rxn)
aziridine (alkylator) |
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Definition
| myelosuppr, stomatitis, N/V/D |
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Term
| mitomycin forms _ radicals, has _ cross links, and is a _ |
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Definition
| oxygen free radical, G-G, vesicant |
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which drug classes decompase spontaneously like nitrosureas/ produce carbonium ion-2
ex- |
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Definition
hydrazine
triazine
procarbazine
temozaline (oral methylating for brain tumros) |
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| causes blisters/extravasation |
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| major ADEs of alkylating agents shown on slide 27 |
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| whcih molecule produced in tumors inactivates alkylating agents? |
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Definition
| glutathione (GSH) (gluathion trnasferases GSTs) are overexpressed in cancers and so make more GSH |
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| two modes of resistance to alkylating agents |
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