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25 Cards in this Set
- Front
- Back
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how does MTX get into a cell? why do people with down syndrome have an issue with MTX? |
uses the reduced folate carrier gene for reduced folate carrier is on chromsome 21 and retarded kids have an extra 21st chromosome, thus more MTX is able to enter and affect cells |
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what is the guanine analog? what is the adenine analog? what is 6MP converted into? what does this drug inhibit? |
6 mercaptopurine fludarabine the active metabolite T IMP (6 thioinosine 5 monophosphate) de novo synthesis of purines |
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what enzyme can effect the toxicity of 6 MP? what does a poor metabolizer of this enzyme cause? Fast metabolizer? |
thiopuirne methyl transferase TPMT, it is highly polymorphic higher levels of active TIMP and methyl TIMP 6 MP is quicly metabolized into the inactive methly 6 mercaptopurine |
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what are the cytosine analogs? what is the uracil anaolog? what does capecitabine an analog of ? |
cytarabine and gemcitabine 5 FU does not resemble any specific base |
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how does 5 FU work? what does the combo of leucovorin with 5 FU do? |
converted to Fdump which competes with dUMP for binding to thymidylate synthase, thymidlyate synthase is locked up by fdUMP and prevents DNA synthesis supposed to increase 5FU activity and used for colorectal cancer |
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is capecitibine oral or IV? what does the liver metabolize it to? what does this metabolite get metaoblized into? what enzyme does this? why would this drug be more active in colon cancer? |
oral 5 DFCR thymidine phosphorylase makes active 5 FU tumor cells have elevated thymidine phosphorylase activity resulting in higher concentrations of 5 FU in tumor cells and not healthy cells |
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what enzyme metabolizes 5 FU? what does reduced DPD function cause? is it better to phenyotype or geneotype this gene? how would you do this? |
dihydropyrimidine dehydrogenase or DPD less excretino so toxicity of 5 FU and possibly capecitibine phenotype since you could actually measure actual function use a radiolabeled uracil |
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if your heterozygous for a DPD mutation, will it have that much effect? |
Yes, could decrease clearance by 50%, would be fatal if you were homozygous |
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what are the components of a nitrogen mustard? what is the intermediate that is formed and what does this cause? what base does it affect? are any other genes affected? |
an ethyl group and a chlorine carbonium ion, this binds to imidazole nitrogens in DNA, results in G and T mispairs guanine p53 is activated and may cause apoptosis |
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What enzymes metabolize cyclophosphamide? what is the active metabolite and which enzyme creates it? what is the tox compound that is made along with the active metabolite? |
mainly CYP2B6 and a little of CYP 3A4 2B6 and it leads to active phosphooramide mustard acrolein |
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what can acrolein cause? how do you neutrolize it? how does that work? what does this protect? |
hemorrhagic cyctits, hurts kidney and bladder use MESNA thiol group on mesna prevent acrolein from binding to the cysteine on normal healthy proteins of cells only the bladder, not the kidney |
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what is the toxic metabolite that cyclophosphamide is metabolized into by the CYP3A4? what does this damage? what would be the result if you inhibit 3A4? |
chloro acetaldehyde is a nephrotoxin and neurotoxin less tox |
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how is ifosfamide different than cyclophosphamide? how does this affect tox? |
it is metabolized by 3A4 more than 2B6 more nephro and neuro tox from choloracetaldehyde, and acrolein is still made this is more tox in general and leads to renal failure and cns depression |
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what is the primary function of platinum drug? what mistakes does it cause in dna? |
bind to dna and cause apoptosis of cancer cells guanine guanin intrastrand adducts, adenine guanine intrastrand adducts, interstrand crosslinks |
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what is the function of topo 2? function of topo 1? why do we care about these in cancer? |
causes a double strand break in dna in order to prepare it for winding into supercoils, then reseals the dna after condensation relaxes dna to allow replication and transcription to occur, makes single strand breaks and reseals tipo inhibitors work after dna has been broken, preventing religation which causes dna damage and cell death |
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what job of the topos do the drugs inhibit? what are the two topisomerase 2 inhibitors? |
the religation to fix the nick the enzyme creates doxorubicin and etoposide |
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what causes the acute anthracycline cardiotox? what drug is used to prevent this harm? how does it work? |
the fenton reaction that creates a hydroxy radical, this damages dna and lipids causing acute dysfunction dexrazoxane iron chelator, may also reduce efficacy of anthracycline |
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what causes the chronic cardio tox from anthracyclines? does this adverese reaction increase linearly with dose? |
enhance calcium loading into the sarcoplasmic reticulum which results in hypertrophy and a reduced ejection fraction, then heart failure does not, increases exponentially, tox accumulates over entire treatment regimen |
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what are the topo 1 inhibitors? what topo 1 inhibitor is a prodrug? what is the active metabolite and what enzyme does this conversion? |
camptothecin, irinotecan, topotecan irinotecan carboxylesterase in blood SN 38 |
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how is SN 38 metabolized? what enzyme does this? what does an impairement of this enzyme cause? |
it undergoes glucuronidation UGT1a1 worse irinotecan and sn 38 tox, since it cant be eliminated |
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where do mutations in the ugt1a1 gene occur in? what does this region of the gene do? |
not the coding sequence itself, but in the promoter of the gene, the only difference is in the amount of protein produced tells how fast to make RNA and protien and alters concentration of the protein |
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what binds the promoter region? what mutation puts you at risk for irinotecan? |
transcription factors ugt1a1 *28/*28 |
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do epigenetics alter dna sequence itself? what does methlylation of a gene cause? what does acylation of histones cause? |
no, just methylates or demethylates, or acetylates or deacetylates reduced expression enhanced gene expression |
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what does histone deacetylase do? what is the result from this? when might HDAC cause cancer? why does aceylation cause more transcription? |
removes acetyl grops from histones and causes reduced gene expression if it is overactive near a tumor suppressor gene acetylating lysine removes postivie charge and thus relaxes the dna for access of enzymes since there is no ionic bond |
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what is the only HDAC inhibitor drug? what does it do? |
vorinostat prevents deacetylations of histones which causes enhances expression of tumor suppressor genes |
