Chemotherapy and antineoplastics

Question 1

What are your folic acid analagoues?

Answer 1

Methotrexate

Question 2

What the pyrimidine analagoues?

Answer 2

5-Fluorouracil

Question 3

Cytidine analogues?

Answer 3

cladribine, azacitidine, decitabine, gemcitabine

Question 4

purine analogues?

Answer 4

6-thiopurine analagoues

Question 5

What is an antimetabolite?

Answer 5

substance that competes with repplaces or inhibits a specific metabolite-intereferes with normal cell metabolic functioning

Question 6

Antimetabolites MOA:

Answer 6

competititve inhibition-halts cell growth and cell division
intereferes with DNA synthesis and cellular function

Question 7

Folate is known as?

Answer 7

Vitamin B 9

Question 8

Folic acid is converted to? (active form)

Answer 8

tetrahydrofolate (FH4)

Question 9

FH4 does what?

Answer 9

methyl group donor (reducing folic acid) for the synthesis of thymidine

Question 10

Folic acid analogues MOA?

Answer 10

block the formation of thymidine—>purine nucleotide imbalance, ultimately slowing DNA synthesis

Question 11

Methotrexate MOA

Answer 11

directly inhibits folate-dependent enzymes of de novo purine synthesis and thymidylate synthesis

Question 12

MTX intereferes with ______ and inhibits ________

Answer 12

FH4 metabolism
inhibits DNA replication

Question 13

Folate antagonists kill during which phase of the cell cylce>

Answer 13

S phase (most effective when cells proliferate rapidly)

Question 14

Can terminate toxic effects of MTX using?

Answer 14

Leucovorin (repletes FH4 cofactors)

Question 15

Leucovorin MOA?

Answer 15

converts into FH4 and bypasses the inhibition of DHFR by MTX

Question 16

Folic acid analogues are?

Answer 16

polar-poorly crosses the BBB
Need: folate receptor, transporter that is active in low PH, and a reduced folate transporter

Question 17

MTX inside cell» enzyme folylpolyglutamate synthesase (FPGS) does what?

Answer 17

adds additional glutamyl residues

Question 18

polyglutamation serves as>

Answer 18

mechanism for ion trapping within cell, prolonged retention of MTX, and greater affinity

Question 19

MTX-PGs constitute?

Answer 19

intracellular storage forms of folates and folate analogues that increase inhibitory potency of Thymidylate synthase (TS).

Question 20

Resistance to antifolates?

Answer 20

impaired transport of MTX
Altered forms of DHFR that have decreased affinity
increased concentrations of intracellular DHFR through gene amplification
decreased ability to synthesize MTX-PGs
increased drug efflux transporter of multi resistant protein

Question 21

Large doses of MTX

Answer 21

must be given IV as they are absorbed incompletely in GI tract

Question 22

MTX IV, drug disappears in triphasic fashion meaning?

Answer 22

rapid distribution
renal clearance of 2-3 hr
terminal phase of about 8-10 hr

Question 23

MTX excretion?

Answer 23

90% excreted unchanged in the urine—>dose adjust for renal failure

Question 24

MTX and highly protein bound drugs interaction?

Answer 24

may displace MTX from albumin and increase toxicity
Sulfonamides, salicylates, phenytoin, tetracyclines

Question 25

Vitamin C and MTX?

Answer 25

could acidify the urine and increase MTX in plasma

Question 26

MTX is critical in the management of what cancer in children?

Answer 26

Acute Lymphoblastic leukemia (ALL)

Question 27

What are the primary toxicities of antifolates?

Answer 27

bone marrow and intestinal epithelium

Question 28

pyrimidine analogues are _____ phase specific agents

Answer 28

S

Question 29

Pyrimidine analogues are AKA

Answer 29

nucleoside analogues, antimetabolites interfering or competing with nucleoside triphosphates in synthesis of DNA and RNA

Question 30

Which agents are analogues of cytosine?

Answer 30

azacitidine, decitabine, cytarabine, gemcitabine (DAC-G)

Question 31

Which agents are analogues of uracil?

Answer 31

Fluorouracil, floxuridine, capecitabine (FCF)

Question 32

Fluorouracil (5FU) MOA:

Answer 32

inhibits thymidylate synthase (TS)--->DNA strand breakage dude to TS inhibition

Question 33

what is the active metabolite of 5FU?

Answer 33

FdUMP

Question 34

how is 5FU administered?

Answer 34

IV (parenterally) due to oral ingestion being unpredictable

Question 35

5FU excretion in urine?

Answer 35

only 5-10% of dose is excreted in urine

Question 36

5FU is inactivated by?

Answer 36

reduction of pyrimidine ring carried out by Dihydriopyrimidine Dehydrogenase (DPD)

Question 37

Leucovorin and 5FU?

Answer 37

enhances rsponse to 5FU but enhances both cytotoxicity and toxicity of Fluorouracil

Question 38

MTX and 5FU?

Answer 38

MTX when given prior to 5FU can enhance activity of 5FU

Question 39

Capecitabine is a ?

Answer 39

orally administered prodrug of 5FU

Question 40

Cytarabine and Gemcitabine MOA:

Answer 40

structural analogue of cytidine and deoxycytidine

Question 41

Cytarabine and Gemcitabine are

Answer 41

potent competitive inhibitors (triphospahte form) of DNA polymerase

Question 42

Decitabine MOA?

Answer 42

induces double strand DNA breaks

Question 43

Azacitidine MOA?

Answer 43

enter cells by ENT1 and gets incorporated into DNA causing demethylation resulting in tumor cell differentiation and apoptosis.

Question 44

Purine analogues do what?

Answer 44

interfere with or compete with nucleoside triphosphates in the synthesis of DNA or RNA -Adenine and Guanine

Question 45

Which drugs are purine analogues?

Answer 45

Mercaptopurine (6MP) and Thioguanine (6TG) (both are prodrugs)

Question 46

Purine analogues inhibit?

Answer 46

T-lymphocytes (reducing CD4 counts) this requires prophylactic medications for infection prophylaxis

Question 47

6MP can be metabolized to inactive metabolite BY?

Answer 47

Xanthine Oxidase dose reduce if given with allopurinoll

Question 48

Cladribine is a ?

Answer 48

prodrug and requires phosphorylation by deoxycytidine kinase to 2CdATP

Question 49

Cladribine AKA?

Answer 49

Adenosine deaminase-resistant purine analogue

Question 50

Fludarabine Phosphate is?

Answer 50

a prodrug (purine analogue)

Question 51

Pentostatin is a

Answer 51

Purine analogue inhibitor of adenosine deaminase (ADA) causes myelosuppression