20 Questions
What is the enzyme that methotrexate competitively inhibits?
Dihydrofolate reductase
Which neoplasms can methotrexate be used to treat?
Leukemia and osteogenic sarcoma
At what urine pH should patients receiving high-dose methotrexate have their urine maintained?
Above 7 / Alkaline
What percentage of methotrexate is bound to plasma proteins?
Approximately 50%
What is the most important minor metabolite of methotrexate with weak activity?
$7$-hydroxy-methotrexate
To ensure that methotrexate toxicities do not occur, what should the urine pH be maintained at during moderate and high-dose treatment?
${Above }7$ / Alkaline
What is the solubility of $7$-hydroxy-methotrexate compared to methotrexate?
One-third to one-fifth as soluble.
What route should be used for administering methotrexate when doses exceed $30$ mg/m${2}$?
Parenteral
What is the concentration of the metabolite $7$-hydroxy-methotrexate compared to methotrexate?
1/200th the clinical activity of methotrexate.
What is the critical value of methotrexate plasma concentration that should be achieved within 48 hours to prevent serious toxicity?
1x10^-7 molar
When is leucovorin administered in case of high methotrexate concentration?
Every 4 to 6 hours from 12 to 72 hours
What is the therapeutic plasma concentration of methotrexate for less than 48 hours?
$>0.1$ micromolar
What is the most common toxic effect of methotrexate?
$\text{Myelosuppression}$
Which metabolite can cause damage to the liver, lung, nerve, and kidney?
$\text{7-hydroxy-methotrexate}$
Why should methotrexate plasma levels be monitored when adding drugs to the regimen following therapy initiation?
To avoid salicylate-induced toxicity
How does leucovorin enhance the anti-cancer effect of 5-FU?
By enhancing the binding of 5-FU to enzyme
What role does leucovorin play in determining the quantity and duration of leucovorin rescue required for methotrexate therapy?
It determines both quantity and duration
Why should drugs be used cautiously in patients receiving prolonged methotrexate infusions?
Due to possibility of inhibition of methotrexate renal clearance
What is the purpose of monitoring Methotrexate levels until they drop below a certain concentration?
To determine if the patient is rescued from toxicity
What effect does using Leucovorin with 5-FU have on the severity of side effects of 5-FU?
Increases the severity of 5-FU side effects
Study Notes
Methotrexate and Leucovorin Therapy: Key Points
- Methotrexate plasma concentration should fall below the critical value of 1x10^-7 molar within 48 hours to prevent serious toxicity.
- Leucovorin is administered every 4 to 6 hours from 12 to 72 hours or the leucovorin rescue dose is increased to 50 to 100 mg/m2 for over 48 hours in case of high methotrexate concentration.
- Oral absorption of methotrexate is complete and rapid, requiring increased leucovorin rescue doses.
- Therapeutic plasma concentration of methotrexate is above 0.1 micromolar for less than 48 hours, while toxic concentration is above 1x10^-7 molar for 48 hours or more.
- Methotrexate is a chemotherapeutic agent used in cancer cells to inhibit dihydrofolate reductase and cause folic acid deficiency, leading to cell demise.
- Most common toxic effects of methotrexate include myelosuppression, oral and gastrointestinal mucositis, acute hepatic dysfunction, low white blood counts, low platelet count, anemia, and hair loss.
- Leucovorin is used for methotrexate toxicity and its metabolite, 7-hydroxy-methotrexate, can cause liver, lung, nerve, and kidney damage.
- Methotrexate plasma concentration should be monitored to avoid salicylate-induced toxicity, and all drugs should be added cautiously to the regimen following the initiation of therapy.
- Methotrexate plasma levels should be monitored to assess efficacy, and leucovorin enhances the anti-cancer effect of 5-FU.
- Leucovorin is used as an adjunct to chemotherapy drugs like methotrexate and 5-FU and is well tolerated, but its side effects may vary when combined with methotrexate.
- Methotrexate and leucovorin therapy is essential for cancer treatment, and monitoring methotrexate levels is crucial for determining the efficacy of the treatment.
- Leucovorin is vital in determining the quantity and duration of leucovorin rescue required for methotrexate therapy, and it should be used cautiously in patients receiving prolonged methotrexate infusions.
Test your knowledge about the folic acid anti-metabolite that competitively inhibits dihydrofolate reductase and its use in treating neoplasms such as leukemia, osteogenic sarcoma, and breast cancer. Explore the administration and dosing regimens of this medication.
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