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pharm chemo 2 Flashcards

1
Q

what is the normal MOA for folic acid?

A
  1. tetrahydrofolate gains a methyl group and forms 510 methyltetrahydrofolate
  2. 510 changes dUMP to dTMP AND it turns into dihydrofoalte via TS enzyme
  3. dihydrofolate turns into tetrahydrofolate via dihydrofolate reductase enzyme
  4. cycle repeats

very IMPORTANT FOR DNA SYNTEHSSI OF CELL
tetrahydrofolate is needed to make AA/protein/DNA/purines

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2
Q

what is the AICAR enzyme?

A

it helps folate participate in de novo synthesis of purines

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3
Q

what group is methotrexate part of ?

A

folic acid analogs

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4
Q

what group is pralatrexate part of ?

A

folic acid analogs

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5
Q

what group is pemetrexed part of ?

A

folic acid analogs

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6
Q

what kind of cell cylce phase does methotrexate work on?

A

S PHASE SINCE IT EXERT ITS EFFECT ON THE DNA PHASE

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7
Q

what is the many MOA for methotrexate?

A
  1. MTX is taken up by the cell via folate transporter
  2. MTX becomes polyglutamated
  3. MTX gets trapped in the cell and INHIBITS TS ENZYME so tetrahydrofolate cannot be made
  4. OR MTX can inhibit dihydrolate reductase so dihydrofolate accumaltes –> inhibits TS and does apoptosis
  5. OR MTX can inhibit synthesis of purines
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8
Q

what is the pharmokokineteics for MTX

A
  • excreated in the kidney becareful with kidney dz
  • builds up in 3rd space so can casue asicites
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9
Q

what drug would u give choriocarcinoma?

A

MTX or any of the folic acid analog

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10
Q

for what would you give POMP?

A

ALL, other leukemias/lymphomas

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11
Q

what drug would u give for osterosarcoma?

A

MTX with leuocovin (have that resuce)

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12
Q

what else is MTX goodfor? ? WHAT is it good for?

A

it has ANTI inflammatory properties
1. low dose MTX - it inhibits DR and TS and will decrease production of inflamamtory cell
2. inhibits Aicar enzymes - when AICAR is inhibited, adenosime builds up which has anti imflammatory propertios

LOW DOSE MTX good for RA inflammatory disorders psoriasis

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13
Q

what are the toxicities of MTX?

A
  1. myleosupression, GI, alopecia, dermatitis
  2. impaired oogenesis/spermatogensis
  3. cirrohosis, teratogensis
  4. abortifacient - combine with misoprostol to kill babies
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14
Q

how do cancer cells develop resistence of MTX?

A
  1. cell can alter folate transporter so DEC untake of MTX
  2. alter DHFR enzyme so dec affinrity of MTX
  3. increased DHFR - overexpression so MTX has no effect
  4. inc effelux - pump MTX out of the cell so no effect
  5. decrease polyglutamation - needed for MTX to work
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15
Q

what is the effect of having HIGH DOSES OF MTX?

A

if u have high doses of MTX, then you really dont need a transporter bc it will go into the cell eventually but high dose will be toxic

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16
Q

when do you give lecovorin and what is it ?

A

leucovorin is a folinic acid whic his taken up BY ONLY HEALTHY CELLS, NOT CANCER CELLS - rememebr this

so you give a huge dose of MTX and MTX Will be taken up by cancer cell and kill it, healthy cells will take up leucovorin and use it for metabolic needs

so you give MTX and leucovorin tg called the leucovorin rescue

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17
Q

what are purine analogs?

A

they are durgs that have sulfar groups which helps bring the drug INTO THE CELLs

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18
Q

what group is 6-thiopurine analogs part of ? what are two examples?

A

part of purines analogs
6MP
6TG

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19
Q

which drug would u give for osterosarcoma?

A

MTX

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20
Q

what drug class is fludarabine part of?

A

purine analogs

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21
Q

what drug class is cladribine part of?

A

purine analogs

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22
Q

what drug class is nelarabine part of?

A

purine analogs

23
Q

when would u give fludarabine? what class?

A

purine analogs
give for CLL

24
Q

when do you give cladribine? what class?

A

purine analogs
hairy cell leukemia, CLL

25
when would you give nelarabine? what class?
pruine analog ALL
26
what is the MOA for purine analogs? tell me for 6MP
1. 6MP is taken up by cancer cell AND healthy cells --> undergoes transformation by HPRT --> turns into 6TIMP (monophosphate) and goes CRAZY in the cell 2. 6TIMP stops purine syntehssi and ribose sugar 3. 6TIMP --> 6TITP (triphosphate) --> goes into DNA/RNA and kills it + stops elongation
27
what is the MOA for purine analogs? tell me for 6TG
1. 6TG goes into cancer cells --> gets converted to 6thioGMP via HPRT 2. 6thiGMP gets converted to triphosphate form --> goes into DNA/RNA and kills
28
what enzymes metabolzies 6MP and keeps the levels high?
XO, xanthine oxidase
29
what inhibits XO?
alopurinol
30
what is azathioprine and its indication?
it is the prodrug of 6MP and its given for lamber eaten MS, inflammatory disorders, immunosupression if someone is on organ transplant
31
when do you give 6MP and 6TG?
6MP - ALL (POMP regime) 6TG - AML (with cytarabine)
32
what are the toxicities for purine analongs?
1. myleosupression can lead to anemia, thrombocytopenia, leukopenia 2. GI 3. teratogenic 4. 6MP can lead to AML if taken for a long time
33
what group is 5FU part of ?
fluropyramidine (pyramide analogs)
34
what group is Capecitabine part of?
* Fluoropyrimidines (pyramidine analog)
35
what group is floxuridine part of ?
Fluoropyrimidines (pyramidine analog)
36
what group is cytarabine part of ?
cytidine analogs - pyramidine analogs
37
what group is gemcitabine part of ?
cytidine analog - pyrimidine analogs
38
what group is 5-azacytidine part of ?
cytidine analog - pyrimidine analogs
39
what group is decitabine part of ?
cytidine analog - pyrimidine analogs
40
what is hte MOA for 5FU?
1. 5FU is taken up by the cell and converted into nucleotides which can be for oxy or deoxynucleotide (DNA/RNA) 2. fUMP will become triphosphate --> go into RNA --> damage or it can go into deoxy DNA -->damange, no pairing, brekafast, poor protein syntehssi 3. fDUMP will inhibit thymidylate synthase 4. TS-folate-FdUMP will create a huge covalent bond --> TS cannot trasnfer methly group over to uracial --> dies
41
what pyridime analog will inhibit TS?
fDUMP
42
when would you give 5FU and leucovorin?
normally cancer cells WONT take up leucovorin EXCEPT in colorectal tumors
43
what combo inhibits thymidylate synthase ?
TS-folate-FdUMP
44
what drug combo inhibits TS? with 5FU
5FY + MTX
45
what drug combo will also inhibit TS with 5FU?
5FU + oxaliplatin good for colorectal cancers it will bind to N7 of guanine and inhibit TS
46
what is the best regime for colorectal cancer ?
FOLFOX 5FU, follinic acid, oxaliplatin
47
how can cancer cells become resisitant to pyramidine analogs ?
* Modification of activation enzymes – the enzymes that convert to 5FU into the nucleotide will be modified * Amplification of TS – OVERexpression TS, cant form too much TS, no covalent bond * Mutation of TS or express degradative enzymes
48
when do u give capecitabine? what kind of drug is it
prodrug of 5FU acitvatd in liver, used for breast and colon cancer
49
when do you give floxuridine?
its injected to hepatic artery, given for metasatic LVIER cancer
50
what is the MOA for cytosine arabinoside?
normally the molecules will have OH in the CIS postion but cytosine arabinoside will have OH in the trans postion. this will prevent base paring and cause disruption
51
what is the MOA for cytarabine ARAC (cytosinde arabinoside)
ARAC is taken up by cell via nucleoside transporter ARA-C gets converted into ARA-CTP goes into DNA blocks elongation --> apoptosis
52
when do you use ARA-C?
AML ALL CML lymphomas
53
what drug causes pulmonary edema? what other toxic effect does it have?
ARA-C myleosupression, GI/stomatitis, dermatitis, conjunctitis

pharm 2 (3 decks)

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