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Exam 1
Lecture 4- Platinum Compounds
36
Aerospace Engineering
Undergraduate 2
01/26/2014

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Term
cisplatin was discovered by applying an electrical field to-
Definition
E. coli
Term
cisplatin is curative for-
Definition
testicular cancer
Term
cisplatin prolongs survival in?
also used in-4
Definition
ovarian cancer
head, neck, baldde,r lung
Term
what is the most freq used anticancer agent
Definition
cisplatin
Term
cisplatin has what toxicites-
Definition
renal and neuro
Term
what other drugs have similar effiacy but less ADEs-
Definition
oxalpatin
carboplatin
Term
how are platinum agents similar to alkylating
Definition
they are displaced by nucelophillic attacks to form covalent bonds
Term
what is the target of cisplatin
Definition
N-7 guanine
Term
what platinum drug is used with 5-FU for colon cancer
Definition
oxaliplatin
Term
why are trans-platinums inactive?
Definition
inability of the isomers to form DNA cross links
Term
Cisplatin formed more intra/interstrand cross links
Definition
90% intrastrand (the trans-cis does inter)
Term
carboplatin has less _ than cisplt? 3
has more?3
Definition
nephrotox (subst Cl), neurotox, N/V
stability and Pk predictability, marrow tox
Term
the majority of adducts formed by cisplt and carboplat?
what is 2nd?
Definition
G-G intrastrand XL 60%
A-G intrastrand XL
Term
what crosslinks account for cytotoxicity of platinum drugs?
Definition
intra-strand
Term
diff in oxiplatin adducts from the tohers-2
what does it look like?
Definition
hydrophobic
bulkier
DNA-protein XL (not strnad)
Term
consequences of DNA adduct-2
Definition
preoteins that participate in DNA rxns may become abnormal
processes controlled by proteins that recognize damaged DNA may be activated
Term
cisplatin:
high/low prot bound?
half life?
eliminated thru?
Definition
high
30 min
renally
Term
dose of cisplatin
Definition
50 mg IV q 3 wks
Term
look at slide 13 for a quick overview of cisplatin before test
Definition
Term
the diff in pk for cicplt and carboplt is
Definition
slower conversion of carboplatin to reactive subst
Term
disspaereance of platinum after carboplatin IVs is biphasic- occurs in _ min
Definition
12-98
Term
the clearence of carboplatin is closely related to?
Definition
GFR, renal funciton
Term
dosing of carboplatin is done by?
Definition
AUC
Term
carboplatin might have _ cleaving it to beocme more active in cells than IV
Definition
esterases
Term
Paraplatin
Definition
carboplatin
Term
Eloxatin
Definition
Oxaliplatin
Term
elimn of oxiplatin is -
Definition
biphasic
Term
half life of inital and terminal phases for oxiplatin
Definition
26 min, 38 hrs
Term
oxiplatin has prolonged retention where
Definition
RBCs
Term
unlike cisplaitin, oxalpplatin doesnt accum after courses, this means:
Definition
neurotx is reversible
Term
oxiplatin is excreted mianly by
Definition
renal
Term
toxicites for oxiplatin are when its added to flurouricil : 3
Definition
myleosuppre, stomatitis, neuropathy
Term
can prevent nephrotox of cisplatin with
Definition
amifostine
Term
look at slide 18 for table overview of toxicite sof the agents!
Definition
Term
tumor resistance pathways-3
Definition
glutathione conjugation (by adenosine triphosphates)
metallothioneins and other sulfahydryls inactivate it
increase platinum-DNA adduct repair/ damage tolerance
Term
what are the sufahydrl groups used to prevetn platinum ADes-3
Definition
MESNA
sodium thiosulfate
amifostine
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