Pyrimidine and Purine Analogs Flashcards Preview

NUR2790 (Exam #1) > Pyrimidine and Purine Analogs > Flashcards

Flashcards in Pyrimidine and Purine Analogs Deck (26)
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1
Q

All Pyrimidine Analogs

A
Fluoruracil (5-FU)
Fluxuridine
Capecitabine
Cytarbine
Gemcitabine
2
Q

5-FU Use

A

• GI, pancreas, head & neck, colon, rectum, breast, and ovarian cancer

3
Q

5-FU MOA

A
  • Phosphorylated to 5-FUTP and 5-FdUMP (tight-binding inhibitor of thymidylate synthase)
  • Fluororibonucleotides are incorporated into RNA and perturb RNA processing (splicing, transport, translation)
  • Fluorodeoxyuridines are incorporated into DNA → strand breaks
4
Q

5-FU Cytotoxic MOA

A

5-FU is converted to 5-FdUMP which competes with dUMP for the enzymes thymidylate synthetase
o Normally TS + N5N10 use dUMP to make dTMP but this is blocked by 5-FU
o The N5N10 is then converted to dihydrofolate at the loss of the methyl group to dUMP

5
Q

FdUMP MOA

A

o Enzymes tries to use FdUMP making it unable to transfer the methyl group and you end up with a dead end complex because they just get stuck together

6
Q

5-FU + Leucovorin

A
  • More inihibition of TS → more anticancer effect

* Called “biochemical modulation”

7
Q

5-FU Side effects

A
  • Bone marrow suppression
  • Stomatitis and mucotitis
  • N/V
  • Cardiac
  • Hand & Foot syndrome (lots of rashes on hands and sole of feet)*****
8
Q

Cytarabine Use

A

Acute leukemias

9
Q

Cytarabine Drug Class

A

Analog of CTP - only difference is the sugar used (arabinose)

10
Q

Cytarabine MOA

A

Incorporated into DNA and inhibits chain synthesis via a lack of OH preventing phosphodiester bonds → DNA fragmentation; inhibits DNA polymerase alpha
MOST SPECIFIC FOR S PHASE!!!***

11
Q

Cytarabine SE

A
  • Severe myelosuppression
  • Stomatitis
  • Hand & Foot syndrome
12
Q

Capecitabine Use and MOA

A

 Use: Breast Cancer

 MOA: prodrug of 5-FU

13
Q

Gemcitabine Use

A

Metastatic pancreatic cancer

14
Q

Gemcitabine MOA

A

Phosphorylated to monophosphate then to di and triphosphate
• Triphosphate inhibits DNA polymerases (terminates elongation)
• Diphosphate inhibits ribonucleotide reductase

15
Q

All PURINE analogs

A

Fludarabine
Mercaptopurine
Thioguanine

16
Q

Fludarabine Use

A

CLL (leukemia)

17
Q

Fludarabine MOA

A
  • Phosphorylated inhibition of DNA polymerases

* Incorporation into the DNA strand to leads to chain termination

18
Q

Fludarabine SE

A

Myelosuppression
Neurotoxicity
Pulmonary toxicity

19
Q

6-MP MOA

A

Inhibits the first step in purine biosynthesis

20
Q

Thioguanine (6-TG) MOA

A

Incorporated into DNA/RNA and causes fragmentation

21
Q

6-MP and 6-TG Activation

A

Activated by HGPRT to toxic nucleotides that inhibit several enzymes involved in purine metabolism

22
Q

6-MP + Allopurinol MOA

A

 6-MP is metabolized in the liver by xanthine oxidase and the inactive metabolites are excreted
 Allopurinol is used frequently to treat/prevent hyperuricemia cause by many anticancer drugs

23
Q

6-MP + Allopurinol Dosing

A

If allopurinol is used with 6-MP then the dose of 6-MP has to be reduced by more than 75% to prevent 6-MP induced myelosuppression, hepatotoxicity, mucosititis and hematotoxicity

24
Q

Fibonucleotide Reductase MOA

A

Catalyzes conversion of ribonucleotide diphosphates to deoxyribonucleotide diphosphates
Activated prior to DNA synthesis and controlled by feedback inhibition

25
Q

Hydroxyurea Use and MOA

A

o Use: leukemia, sickle cell anemia
o MOA: inhibits ribonucleotide reducatase
 Inhibits DNA synthesis without affecting RNA synthesis or other nucleotide pools

26
Q

Downside to hydroxyurea?

A

Cleared rapidly so not used often