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.

Mercaptopurine in particular should also be avoided in clients taking gout medications, like allopurinol or febuxostat, because they increase the risk of toxicity.Now, when a client with chronic myeloid leukemia is prescribed an antimetabolite like hydroxyurea, first perform a baseline assessment, including weight, vital signs, and current symptoms like fatigue, weakness, night sweats, and abdominal fullness.

Next, review your client’s recent laboratory tests results, such as CBC, renal and hepatic function, uric acid, as well as a peripheral blood smear, and confirm a negative pregnancy test as needed.

Lastly, review diagnostic tests, including bone marrow examination results. Next, explain to your client that the medication will help to stop the replication of the cancer cells, and instruct them to take the medication at the same time each day with plenty of water.

Also instruct your client to always wear gloves when handling their medication, and to immediately wash their hands afterwards.

Remind them to take an ordered antiemetic 30 to 60 minutes before taking their hydroxyurea, and stress the importance of taking the prescribed folic acid supplement daily.

Then, review with your client some of the side effects they may experience, such as nausea, vomiting, diarrhea, or constipation.

Explain how the medication increases their risk for infection, and stress the importance of including infection prevention measures in their daily routine, such as frequent hand hygiene, and avoiding large crowds, people with infections, undercooked meats, and live attenuated vaccines.

Prompt your client to contact their healthcare provider if they experience any symptoms of infection, including fever, rash, chills, fatigue, sore throat, or severe diarrhea.

Also, they should notify their healthcare provider for any symptoms of bleeding problems, which could manifest as bleeding gums, nose bleeds, as well as coughing up blood, emesis that looks like coffee ground, or dark, tarry stools.Caution your client to avoid unnecessary sun exposure, and to always wear sunscreen and protective clothing when outside, as well as to report any skin changes like new skin growths or mole changes.

Also, prompt them to report symptoms of pulmonary toxicity, which could present as fever, shortness of breath, cough, and fatigue.

Lastly, caution your clients assigned female sex at birth who can become pregnant, to use a reliable form of birth control while taking this medication, and to let their healthcare provider know right away if they become pregnant.

Finally, while your client is being treated with an antimetabolite like hydroxyurea, be sure to closely monitor for the development of side effects, and especially keep a close eye out for any changes in their CBC.

Lastly, be sure to evaluate for the desired therapeutic response of the medication, including an improvement in symptoms associated with chronic myeloid leukemia.

Alright, as a quick recap… Antimetabolites are medications used primarily for cancer treatment, and include folic acid analogs, pyrimidine analogs, purine analogs, and ribonucleotide reductase inhibitors.

These medications work by disrupting DNA synthesis and cell proliferation, eventually leading to cancer cell death. Important side effects of antimetabolites include bone marrow suppression, as well as toxicity to various organs like the lungs, kidneys, liver, and gastrointestinal tract.

When caring for a client taking an antimetabolite, nursing considerations include performing a baseline assessment, monitoring for side effects, and evaluating the desired therapeutic response.

Client teaching includes safe self-administration, learning to recognize side effects, and when to contact the healthcare provider.