Anticancer Drugs
Question 1. Write A Short Note On The Toxicity Of Methotrexate.
Answer:
Methotrexate is a folate antagonist.
- The toxicity of methotrexate is caused due to overdosages.
- Aspirin and sulphonamides increase the toxicity of methotrexate by decreasing its renal tubular excretion.
- Folinic acid rapidly reverses the toxicity of methotrexate. The folinic acid gets converted to a form of tetrahydrofolate which is utilized by the cells.
- Thymidine also counteracts methotrexate toxicity.
Question 2. Write Short Note On Methotrexate.
Or
Write In Brief On Uses And Adverse Effects Of Methotrexate.
Answer:
Methotrexate is an antimetabolite and is a folate antagonist. The drug has anti-neoplastic, immunosuppressive, and anti-inflammatory effects.
Methotrexate Mechanism Of Action
Methotrexate competitively inhibits the dihydrofolate reductase enzyme and prevents the conversion of dihydrofolic acid to Tetrahydrofolic acid and depletes intracellular tetrahydrofolic acid. Tetrahydrofolic acid is very necessary for the synthesis of purines and thymidylate which in turn are very necessary for the synthesis of DNA and RNA.
Read And Learn More: Pharmacology Question And Answers
Methotrexate Phamacokinetics
Methotrexate is well absorbed in oral administration. It can also be administered IM, IV, or intrathecally. Drug bound to plasma proteins and poorly crosses the blood-brain barrier. Most of the drug is excreted unchanged in the urine.
Methotrexate Uses
As an anti-cancer drug in the treatment of:
- Choriocarcinoma is the choice of drug.
- In acute leukemia
- In Burkitts lymphoma
- In breast cancer
- In non-Hodgkin’s lymphoma
- In osteosarcoma
- In head and neck cancer
Due to its anti-inflammatory and immunosuppressive effects, it is also used in the treatment of
- Psoriasis
- Rheumatoid arthritis
- Inflammatory bowel disease
- In organ transplantation
- In ectopic pregnancy.
Methotrexate Adverse Effects
- Megaloblastic anemia
- Hepatotoxicity on chronic administration
- Bone marrow suppression: It manifests as leucopenia, agranulocytosis, thrombocytopenia, and aplastic anemia. In these patients infection and bleeding are common.
- Immunosuppression: Decreased count of lymphocytes causes immunosuppression and patients are prone to opportunistic infections.
- GIT manifestations: Nausea, vomiting, diarrhea
- Alopecia due to damage of hair follicles.
- Presence of dermatitis and skin rashes
- Gonads: Oligozoospermia and infertility in males; amenorrhea and infertility in females.
- Pregnancy: It produces teratogenic effects.
- Hyperuricemia: Gout and urate stones can occur in the urinary tract because of excessive cell destruction.
- Hepatic fibrosis.
Methotrexate Drug Interactions
- Salicylates/Sulphonamides/Tetracycline: Displace methotrexate bound to plasma protein and increase its free form in plasma causing toxicity.
- NSAIDs and sulphonamides potentiate methotrexate toxicity by interfering with its excretion.
Question 3. Write The Basis Of Folinic Acid Is Given With Chemotherapy For Cancer.
Answer:
Folinic acid is given with chemotherapy for cancer because the chemotherapeutic drugs especially methotrexate is a folate antagonist.
It acts by inhibiting dihydrofolate reductase, blocking the conversion of dihydrofolic acid to tetrahydrofolic acid. So methotrexate is responsible for inhibiting folate-dependent reactions inside the body.
Folinic acid is chemically 5-formyltetrahydrofolate which is more stable than tetrahydrofolate, so it directly acts as an active coenzyme and leads to folate-dependent reactions inside the body.
As folinic acid is given with chemotherapy it results in the resumption of DNA synthesis in normal cells. It is professed that normal cells are rescued more than cancer cells and so the therapeutic index is increased.
Folinic acid can also potentiate the antitumor activity of 5 fluorouracil by enhancing the binding of 5 fluorouracil with the specific enzyme in the cancer cells.
Therefore, folinic acid is given with chemotherapy for cancer.
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