1. What is the best time of day, if any, to administer mercaptopurine? Why? Should it be administered with or without food?

Mercaptopurine should be taken at bedtime because data suggests that the risk of relapse is approximately 2.5 times greater for pediatric ALL patients with >70 weeks DFS who take 6MP in the AM. It should also be taken on an empty stomach (2-3 hours after eating) due to delayed and decreased peak concentrations as well as a decreased AUC.

Chronobiol Int.1993 Jun;10(3):201-4., Pediatr Hematol Oncol.1986;3(4):319-24.

2. Name four major drugs/classes that should be avoided in high-dose MTX and why they should be avoided.

1. Allopurinol: Inhibits xanthine oxidase which is responsible for inactivation of MTX. Should be avoided; if necessary, dose reduce allopurinol by 75%2. SMX-TMP: Trimethoprim has effects on inhibiting DHFR as well as displacing MTX from plasma proteins leading to increased risk of myelosuppression.3. PPIs: Case reports show PPIs may delay MTX elimination resulting in higher concentrations leading to increased toxicity4. Penicillin abx: Inhibit tubular secretion, including that of MTX, leading to increased serum concentrations

3. What is the mechanism of action of methotrexate? How does leucovorin work?MTX inhibits DHFR, TS, and GARFT which prevents the cycle important for the transfer of methyl groups from reduced folate to dUMP ultimately preventing thymine synthesis and this DNA synthesis. Leucovorin is reduced folic acid which is given as rescue for high dose MTX to bypass the inhibition of DHFR and GARFT allowing for pyrimidine synthesis. It is thought to be selective to for normal cells due to decreased polyglutamation of MTX in normal cells.4. What are the two major pathogenic species of Enterococcus? Which species tends to be vancomycin resistant? Vancomycin susceptible?-Enterococcus faecalis: usually vancomycin sensitive-Enterococcus faecium: tends to be vancomycin resistant

5. Describe candida coverage of micafungin versus ambisome versus voriconazole.

Drug1st Line2nd LineNot active

MicafunginC. albicans, C. dubliniesis, C. tropicalis, C. krusei, C. glabrataC. parapsilosis, C. guilliermondii, C. lusitaniae

VoriconazoleC. albicans, C. dubliniesis, C. tropicalis, C. guilliermondii, C. parapsilosisC. krusei, C. lusitaniaeC. glabrata

AmbisomeC. albicans, C. dubliniesis, C. tropicalis, C. glabrata, C. parapsilosisC. guilliermondii, C. kruseiC. lusitaniae

6. Is voriconazole safe to use in patients with renal dysfunction? Does voriconazole cause renal dysfunction?IV voriconazole contains the excipient cyclodextrin which can accumulate in patients with renal dysfunction which may lead to further hepatic and/or renal dysfunction. PO voriconazole can safely be used in renal impairment.

Nephrol. Dial. Transplant.(2011)