Medical Pharmacology: Cancer Chemotherapy
Anti-Metabolite Practice Questions
Click on the correct answer.
Thiopurine anticancer analogues:
6-mercaptopurine (6-MP) was the first thiopurine agent noted to be effective in treating cancer.
6-mercaptopurine is mainly used in childhood acute leukemia treatment.
Both
Neither
Natural purine analogs used for treating human leukemias:
6-thioguanine (6-TG)
6-mercaptopurine (6-MP)
Both
Neither
The parent drugs 6-TG (6-thioguanine) and 6-MP (6-mercaptopurine):
These agents are converted to ribonucleotides 6-thioguanosine (6-thioGMP) and 6-thioinosine-5'-monophosphate (T-IMP).
T-IMP Accumulates intracellularly, eventually converted to 6-TGMP.
T-IMP inhibits ribosyl-5-phosphate formation at the step involving glutamine and 5-phosphoribosyl-1-pyrophosphate. (de novo synthesis pathway: first step)
Thioguanine nucleotide, following incorporation into DNA, causes both strand breaks in base mispairing.
A & B
B & C
A & C
All answers are correct (A-D)
Concerning 6-mercaptopurine (6-MP) metabolism:
An inactive metabolite (6-thiouric acid) is formed from 6-MP by an oxidation reaction catalyzed by xanthine oxidase.
Allopurinol, a purine analogue, used in this setting to reduce the likelihood of hyperuricemia secondary to tumor cell lysis in acute leukemia treatment, is a xanthine oxidase inhibitor.
Use of 6-mercaptopurine with concurrent administration of allopurinol requires the 6-MP dose to be reduced (50%-75%) to avoid high 6-MP toxicity (due to increased 6-MP levels due to xanthine oxidase inhibition)
A & B
B & C
A, B & C
Concerning thiopurine metabolism:
Thiopurines are metabolized in part by thiopurine methyltransferase.
In patients exhibiting a deficiency in this enzyme are subject to increase risks for severe toxicities from thiopurine drug administration.
Both
Neither
6-mercaptopurine toxicity:
The primary 6-mercaptopurine toxicity is bone marrow depression.
Symptoms of bone marrow depression such as thrombocytopenia or anemia develop within 3 to 5 days following administration.
Both
Neither
Infections associated with 6-mercaptopurine and azathioprine administration:
Fungal infections
Pneumocystis pneumonia
Both
Neither
6-mercaptopurine exhibits teratogenic effects during the first trimester pregnancy.
True
False
6-MP and derivative agent azathioprine administration have been linked to an increased risk of skin squamous cell malignancy.
True
False
Administration of thiopurine-anticancer drugs may induce liver toxicity (affecting as many as 30% of adult patients) which presents as cholestatic jaundice.
