chemo lecture 2

Question 1

What are the folate anti metabolite drugs

Answer 1

• Methotrexate

- Pemetrexed

Question 2

what are the purine anti metabolite drugs

Answer 2

• 6 mercaptopurine
• 6-Thioguanine
• Fludarabine
• Cladribine

Question 3

What enzyme does methotrexate inhibit?

This blocks what?

Answer 3

DHFR: dihydrofolate reductase

-blocks synthesis of thymidine, methionine and serine

Question 4

What does pemetrexed inhibit

Answer 4

thymidylate synthase and GAR transformylase

-1000x LESS potent inhibitor of DHFR compared to methotrexate

Question 5

therapeutic uses of methotrexate

Answer 5

• pediatric leukemias
• Primary CNS lymphoma
• NHL
• choriocarcinoma (MONOTHERAPY)

Question 6

Therapeutic use of pemetrexed

Answer 6

-malignant pleural mesothelioma

Question 7

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

Answer 7

“rescue” with leucovorin

Question 8

explain the metabolism and toxicity of High dose methotrexate

Answer 8

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

Question 9

GI toxicities of MTX

Answer 9

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

Question 10

toxicities with intrathecal injection of MTX

Answer 10

neurotoxicity: stiff neck, seizures, encephalopathy, paraplegia

Question 11

clinical significance of pemetrexed

Answer 11

survival benefit with cisplatin in malignant pleural mesothelioma

Question 12

What is 6-Mercaptopurine used for

Answer 12

maintenance of remission in ALL

Question 13

What is Fludarabine used for

Answer 13

CLL

Question 14

what is Cladribine used for

Answer 14

Hairy Cell Leukemia

Question 15

route of administration of fludarabine and why?

Answer 15

ONLY IV to avoid intestinal bacteria generating toxic fluoroadenine

Question 16

explain metabolism of 6-MP IN LIVER

Answer 16

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

Question 17

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

Answer 17

• 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

Question 18

explain role of TPMT in liver vs. other cells

Answer 18

responsible for activation in other cells but inactivation in Liver

Question 19

explain toxicity of 6-MP due to gout meds

Answer 19

-gout meds inhibit xanthine oxidase so you get overexposure

Question 20

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

Answer 20

• Allopurinol

- Febuxostat

Question 21

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

Answer 21

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

Question 22

Xanthine Oxidase and 6-TG

Answer 22

6-TG bypasses the XO inactivation so no drug interaction

Question 23

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

Answer 23

• Fludarabine

- Cladribine

Question 24

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

Answer 24

S phase