Nucleotide synthesis inhib

Question 1

Leflunomide

Answer 1

inhib dihydroorotate –> pyrimidine synthesis
inhib conversion of Carbamoyl phosphate to Orotic acid
cells arrested in G1
Cholestyramine can inc rate of elimination via interruption of enterohepatic circulation
Use as DMARD for RA
CI in prego

Question 2

Mycophenolate

Answer 2

inhib IMP dehydrogenase –> purine synthesis
inhib conversion of IMP to GMP
used in xsplant immunosuppression

Question 3

Ribavirin

Answer 3

inhib IMP dehydrogenase –> purine synthesis
inhib conversion of IMP to GMP
can be used as an antiviral; esp HCV

Question 4

Hydroxyurea

Answer 4

inhib ribonucleotide reductase –> pyrimidine synthesis

inhib conversion of UDP to dUDP

Question 5

6-mercaptopurine / azathioprine

Answer 5

inhib de novo purine synthesis –> purine synthesis
inhib conversion of PRPP to IMP
prodrug = azathioprine
metabolism inhibited by allopurinol = toxicity

Question 6

5-FU

Answer 6

inhib thymidylate synthase –> pyrimidine synthesis

inhib conv of dUMP to dTMP

Question 7

Methotrexate

Answer 7

inhib dihydrofolate reductase –> pyrimidine synthesis

inhib prod of dTMP due to inhibition of conversion of DHF to THF

Question 8

Trimethoprim

Answer 8

inhib dihydrofolate reductase

inhib prod of dTMP due to inhibition of conversion of DHF to THF

Question 9

Pyrimethamine

Answer 9

inhib dihydrofolate reductase

inhib prod of dTMP due to inhibition of conversion of DHF to THF

Question 10

Allopurinol

Answer 10

hypoxanthine isomer
causes irrev inhib of xanthine oxidase –> inc plasma xanthine and hypoxanthine levels
Tx for Lesch-Nyhan Syndrome and gout

Question 11

alpha-amantin

Answer 11

Amanita phalloides mushroom toxin
inhibits RNA Polymerase II
causes severe hepatotoxicity