Pharmacology methotrexate

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Where in the cell cycle does methotrexate act?
S-phase

What is the MOA for methotrexate?
Inhibition of DHFR resulting in depletion of THF & thymidine

What is the dosage range for methotrexate?
7.5mg/m2-35gm/m2

What are the three metabolic pathways of methotrexate?
1. DAMPA-intestinal bacteria
2. 7-OH MTX (primary metabolite-inactive)
3. Polyglutamates

Which of methotrexates metabolic pathways is the primary metabolite?
7-OH MTX (inactive)

Which of the three metabolic pathways of methotrexate allows for it to stay in the cell longer resulting in a better chemo response?
Polyglutamates

What is the primary excretion pathway of methotrexate?
Renal

Methotrexate is primarily excreted by the kidneys via what two ways?
1. Glomerular filtration
2. Tubular secretion & reabsorption

What are the two factors that can alter MTX clearance?
1. Hydration status-measure urine specific gravity
2. Urine pH-must be >6.5 or adjust with NaCO3

What are the top 5 MTX toxicities?
1. Bone marrow suppression-Pancytopenia
2. Mucositis
3. Nephrotoxicity-precipitation of MTX/7-OH in tubules
4. GI desquamation
5. Inadequate leucovorin rescue

What is time that you must start MTX leucovorin rescue by?
36-45 hours after dose

What is the typical [MTX] that you look for until consider at low risk for toxicity?
<0.1mM

What are MTX drug interactions?
Salicylates & Sulfonamides

What 4 things do you monitor to avoid MTX toxicities?
1. Adequate hydration & good urine output
2. Urine pH >6.5
3. Drain pleural effusions prior to MTX
4. Adjust leucovorin rescue based on [MTX]

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