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Flashcards in chemo lecture 2 Deck (24)
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1
Q

What are the folate anti metabolite drugs

A
  • Methotrexate

- Pemetrexed

2
Q

what are the purine anti metabolite drugs

A
  • 6 mercaptopurine
  • 6-Thioguanine
  • Fludarabine
  • Cladribine
3
Q

What enzyme does methotrexate inhibit?

This blocks what?

A

DHFR: dihydrofolate reductase

-blocks synthesis of thymidine, methionine and serine

4
Q

What does pemetrexed inhibit

A

thymidylate synthase and GAR transformylase

-1000x LESS potent inhibitor of DHFR compared to methotrexate

5
Q

therapeutic uses of methotrexate

A
  • pediatric leukemias
  • Primary CNS lymphoma
  • NHL
  • choriocarcinoma (MONOTHERAPY)
6
Q

Therapeutic use of pemetrexed

A

-malignant pleural mesothelioma

7
Q

High dose of Methotrexate in treatment of leukemia and high risk lymphoma must be followed by what?

A

“rescue” with leucovorin

8
Q

explain the metabolism and toxicity of High dose methotrexate

A
  • hepatic rather than renal like lower doses
  • converted to 7-Hydroxy-MTX
  • causes Crystalluria tubular obstruction
9
Q

GI toxicities of MTX

A
  • mucositis
  • small bowel ulcers and bleeding
  • Diarrhea- discontinue to prevent perforation of gut
10
Q

toxicities with intrathecal injection of MTX

A

neurotoxicity: stiff neck, seizures, encephalopathy, paraplegia

11
Q

clinical significance of pemetrexed

A

survival benefit with cisplatin in malignant pleural mesothelioma

12
Q

What is 6-Mercaptopurine used for

A

maintenance of remission in ALL

13
Q

What is Fludarabine used for

A

CLL

14
Q

what is Cladribine used for

A

Hairy Cell Leukemia

15
Q

route of administration of fludarabine and why?

A

ONLY IV to avoid intestinal bacteria generating toxic fluoroadenine

16
Q

explain metabolism of 6-MP IN LIVER

A

goes to the liver then

  • TPMT to methyl-6-MP
  • XO to 6-Thiouric acid
  • both of the above are inactive metabolites
  • the rest goes to other cells
17
Q

explain metablism of 6-MP after the Liver in other cells

A
  • HPRT to TIMP
  • then TPMT takes TIMP to 6-methyl-TIMP ribonucleotides (Most clinically relevant pathway)
  • IMPDH also takes TIMP to TXMP
  • All of the above are active metabolites
18
Q

explain role of TPMT in liver vs. other cells

A

responsible for activation in other cells but inactivation in Liver

19
Q

explain toxicity of 6-MP due to gout meds

A

-gout meds inhibit xanthine oxidase so you get overexposure

20
Q

What are the gout meds to watch out for when giving 6-MP

A
  • Allopurinol

- Febuxostat

21
Q

Explain the role of TPMT in 6-TG metabolism compared to 6-MP

A

TPMT inactivates 6-TG in liver and other cells whereas 6-MP gets activated by TPMT in other cells

22
Q

Xanthine Oxidase and 6-TG

A

6-TG bypasses the XO inactivation so no drug interaction

23
Q

What 2 drugs are chemical analogs of Adenosine that inhibit DNA polymerase

A
  • Fludarabine

- Cladribine

24
Q

What phase of the cell cycle do Folate and Purine antimetabolites inhibit

A

S phase