Antimetabolites: Nursing Pharmacology

Antimetabolites are medications used primarily for cancer treatment. They are most effective against hematologic malignancies, like leukemia, lymphoma, and myelodysplastic syndrome; but they can also be effective against solid tumors, like breast cancer, head and neck cancer, and osteosarcoma.

Based on the specific substance with which they interfere, antimetabolites can be classified into folic acid analogs, like methotrexate, which can be administered orally, subcutaneously, intramuscularly, intravenously, or intrathecally; pyrimidine analogs, like fluorouracil, which can be administered topically or intravenously, and cytarabine, which can be administered subcutaneously, intravenously, or intrathecally; purine analogs, like mercaptopurine, taken orally, as well as cladribine and fludarabine, administered intravenously; and ribonucleotide reductase inhibitors, such as hydroxyurea, which can be administered orally or intravenously.

Okay, the reason antimetabolites are effective for cancer treatment is that they disrupt DNA synthesis.

They do that either by mimicking folic acid, or nucleobases, such as pyrimidines and purines; or by inhibiting enzymes that are involved in the pathway, such as adenosine deaminase and ribonucleotide reductase.

As a result, they stop DNA replication and cell proliferation, eventually leading to cancer cell death. Unfortunately, this action can also increase the risk of serious side effects.

All antimetabolites can cause bone marrow suppression, but this is only a boxed warning for methotrexate, cladribine, fludarabine and hydroxyurea.

Bone marrow depression can lead to leukopenia and an increased risk of infections, thrombocytopenia and an increased risk of bleeding, as well as anemia.

Some clients can also experience gastrointestinal disturbances, such as anorexia, nausea, vomiting, and diarrhea.

GI toxicity is actually a boxed warning for methotrexate, and also more common with fluorouracil, cytarabine and mercaptopurine.

Pulmonary toxicity is yet another boxed warning for methotrexate, and a common side effect of hydroxyurea, which can present as either pulmonary fibrosis or pneumonitis.

Next up, there’s dermatological toxicity, which can present as rashes or skin ulcerations. This is a boxed warning for, you guessed it, methotrexate, and a common side effect for fluorouracil.

Additionally, fluorouracil can cause palmar-plantar erythrodysesthesia, or hand-foot syndrome, which is when the palms and soles of the feet develop redness, swelling, and even blisters.

Nephrotoxicity is a boxed warning for both methotrexate and cladribine, while hepatotoxicity is only a boxed warning for methotrexate, and a common side effect of cytarabine and mercaptopurine.

Neurotoxicity, on the other hand, is a boxed warning for cladribine and fludarabine, and a common side effect of cytarabine.

Fludarabine also has a boxed warning for autoimmune hemolytic anemia and autoimmune thrombocytopenia.

Other common side effects with these medications include drowsiness, fatigue, alopecia, photosensitivity, and ulcerative stomatitis.

And if all that wasn’t enough, here are some more specifics: methotrexate comes with two more boxed warnings: one is for use during pregnancy, because it can cause neural tube defects in the developing fetus; and the second one is for tumor lysis syndrome, which refers to metabolic disturbances that can occur when a large number of cancer cells are killed rapidly.

Fluorouracil can cause cardiotoxicity, and finally, hydroxyurea comes with a risk of developing a secondary malignancy, particularly skin cancer, after prolonged use.

As far as contraindications go, antimetabolites should not be used during pregnancy and breastfeeding because they are teratogens, meaning that they disrupt fetal development and can lead to birth defects.

All antimetabolites should also be used with caution in clients with liver and renal disease. In addition, they’re contraindicated in clients that have a severe infection or myelosuppression.