Chemo drugs reduced 4

Question 1

When do antimetabolites act?

Answer 1

during the S phase

Question 2

Methotrexate

Answer 2

S phase
binds dihydrofolate reductase
-decreases tetrahydrofolate

1. Protein bound: asprin, sulfonamides, pneicillins may displace MTX from albumin leading to toxicity
2. Gains access to ascites and pleural effiusions-contraindication
3. Alter dose for impaired renal function
4. Aspirin, penicillins, probenecid interfere with excretion
5. Alkalinize urine to promote excretion greater than 7
6. High IV dose may provide protection to CNS against spread to tumor

Toxicities: stomatitis

Question 3

What can save a cell from myelosuppression of methotrexate if there is not polyglutamation?

Answer 3

leucovorin

Question 4

pemetrexed

Answer 4

inhibits thymidylate synthase

myelosuppression is dose limiting

rash, stomatitis, diarrhea, and hand food syndrome

Pretreat with vitamin B-12 and oral folic acid decreases extent of myelosuppression

Lung cancer and mesothelioma

Question 5

Cytosine arabinoside

Answer 5

S phase pyrimidine analog

• sequential phosphorylation and is incorporated into DNA
• inhibits DNA polymerase and chain elongation

Schedule dependent cytotoxicity**
-3 days anthracycline and 7 days continuous infusion of cytosine arabinoside

**Intrathecal

-treat leukemia

Question 6

5 fluorouracil

Answer 6

S phase

leucovorin enhances cytotoxicity

• 5FDUMP and leucovorin forms strong inhibitory complex with thymidylate synthesis-thymineless death
• gastrointestinal toxicity also enhanced

metabolized: liver, need DPD, without it severe toxicity (autosomal recessive)-myelosuppression, diarrhea, stomatitis
- frequently given concomitantly with radiation therapy as radiation sensitizer
- toxicity is dependent on schedule of administration

hyperpigmentation of skin of palms and hands, increased sensitivity to sunlight
rarely coronary artery vasospasm and cerebellar toxicity. excess lacrimation and hand foot sydnrome

Question 7

capecitabine

Answer 7

can substitute for IV 5FU
-oral

Rah, diarrhea, stomatitis, hand-food syndrome, myelosuppression

Question 8

6 Mercaptopurine

Answer 8

S phase

• metabolized to 6 thioinosinic acid which inhibits enzymes needed for purine nucleotide synthesis
• metabolized to inactive form by xanthine oxidase (inhibited by allopurinol-decrease dose by 50%)
• myelosuppression dose limiting

Treat: childhood leukemia

Question 9

6 thioguanine

Answer 9

full dose when the patient is also receiving allopurinol