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Antifolate Agents


What are antifolate drugs?

Antifolate drugs, also known as folate antagonists, or antifols, are drugs that restrain the production of folic acid. Folate antagonists cause a deficiency of folic acid that is instrumental in folate-dependant enzymes and their role in cellular production and building processes. This folic acid deficiency hinders the rapid division of cells, their growth, and production.

How are antifolate drugs used?

Cancerous disease treatment

The characteristics of antifolate drugs have played a role in their use to suppress growth of malignant tumors. Some antifolate drugs are used with other chemotherapy drugs to either enhance cancer-fighting characteristics, or as a protectant for healthy cells during chemotherapy treatments.

Folate antagonists are currently used to treat various types of cancer including:

Acute lymphocytic leukemia, non-Hodgkin’s lymphoma, breast cancer, bladder cancer, head and neck cancer, mesothelioma, osteogenic sarcoma and choriocarcinoma.

Non-cancerous disease treatment

Antifolates have also shown to be effective in treating other nonmalignant diseases including: rheumatoid arthiritis, malaria, psoriasis, bacterial infections and plasmodial infections.


Types of antifolate drugs and their side effects

The following are some types of antifolate drugs that are currently being used and some of their associated side effects:

  • Aminopterin (AMT) – This antifolate drug was originally used to help pediatric patients that had leukemia. Eventually the antifol, methotrexate, was used instead because it was shown to be just as effective, but with less toxicity. Some known side effects include: nausea and vomiting, weight loss, fever, renal failure, chills, inflammation in the mouth, pharyngitis and rashes.
  • Methotrexate (MTX) – This folate antagonist is the most commonly used in oncology. MTX is highly effective in treatment of diseases such as choriocarcinoma. It is used by itself and in combination with other drugs. Some known side effects include: anemia, nausea and vomiting, dermatitis, neutropenia, higher incidence of bruising and diarrhea. Patients have an increased risk of developing pulmonary fibrosis and hepatitis.
  • Trimetrexate (TMQ) – This antifol was originally used to help cure bacterial infections. Currently it is used to treat various types of cancer. Trimetrexate keeps cells from using folic acid and as a result they die off. It is used with leucovorin (to curb side effects) and fluorouracil (to boost cancer-fighting characterisitics). Some of the known side effects include: negative effects on bone marrow production, increased risk of infection, anemia, nausea and vomiting, rashes, inflammation in the mouth and increased risk of kidney or liver damage.
  • Fluorouracil – This antifolate drug has been used for about 40 years as a chemotherapy drug. It is primarily used to treat pancreatic and colorectal cancer. Some of the known side effects include: mucositis, dermatitis, diarrhea, effects on bone marrow and cardiac toxicity.
  • Lometrexol (LMTX) – This folate antagonist has been studied and used to attack tumors related to various types of cancers. This drug has been shown to inhibit the production of tumor cells. It has proven to be especially effective in treatment against tumors related to colorectal, breast, pancreatic, lung and head and neck cancers. Some of the known side effects include: dehydration, weight loss, anemia, inflammation of mucous membranes, increased risk of infection and patients may be slow to react in physical and mental activities.
  • Pemetrexed – This antifolate drug is used in chemotherapy treatment. This antifol affects rapid cell growth. Pemetrexed is used to treat lung cancers such as mesothelioma. Some side effects include: anemia, fatigue, nausea and vomiting, constipation, chest pain, shortness of breath, fever, depression, numbness in hands or feet, poor appetite, fever, flu-like symptoms and skin irritation. More on pemetrexed side effects.


 




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