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Antimetabolites: Nursing Pharmacology

Notes

Notes

ANTIMETABOLITES, PART 1/2
DRUG NAME
methotrexate (Otrexup, Rasuvo, Trexall, Xatmep)
*High Alert Medication*

fluorouracil, cytarabine
*High Alert Medications*

CLASS
Folic acid analogs
Pyrimidine analogs
MECHANISM of ACTION
Mimic folic acid or nucleobases or inhibit enzymes → disrupt DNA synthesis pathway → DNA replication and cell proliferation come to a halt → cancer cell death
INDICATIONS
Cancer treatment:
  • Hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndrome) 
  • Solid tumors (e.g., breast cancer, head and neck cancer, osteosarcoma)
ROUTE(S) of ADMINISTRATION
  • PO
  • SubQ
  • IM
  • IV
  • Intrathecal
  • IV
  • TOP (fluorouracil)
  • SubQ (cytarabine)
  • Intrathecal (cytarabine)
SIDE EFFECTSBoxed warnings: 
  • Bone marrow suppression 
  • Pulmonary toxicity 
  • GI toxicity 
  • Dermatologic toxicity 
  • Nephrotoxicity 
  • Hepatotoxicity 
  • Tumor lysis syndrome 
  • Pregnancy

Both:
  • Bone marrow suppression
  • Oral, GI ulceration (GI toxicity)

Fluorouracil
  • Hand-foot syndrome
  • Cardiotoxicity
  • Dermatologic toxicity

Cytarabine
  • Hepatotoxicity
  • Neurotoxicity
Other common side effects for all medications: drowsiness, fatigue, alopecia, photosensitivity, and ulcerative stomatitis
CONTRAINDICATIONS & CAUTIONS
  • Pregnancy 
  • Breastfeeding
  • Liver and renal disease
  • Severe infection
  • Myelosuppression
  • Clients taking gout medications (allopurinol / febuxostat) → increased risk of toxicity  
ANTIMETABOLITES, PART 2/2
DRUG NAME
mercaptopurine, cladribine,
fludarabine
*High Alert Medication*

hydroxyurea (Droxia, Hydrea, Siklos)
*High Alert Medication*

CLASS
Purine analogs
Ribonucleotide reductase inhibitors
MECHANISM of ACTION
Mimic folic acid or nucleobases or inhibit enzymes → disrupt DNA synthesis pathway → DNA replication and cell proliferation come to a halt → cancer cell death
INDICATIONS
Cancer treatment:
  • Hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndrome) 
  • Solid tumors (e.g., breast cancer, head and neck cancer, osteosarcoma)
ROUTE(S) of ADMINISTRATION
  • PO (mercaptopurine )
  • IV (fludarabine, cladribine)
  • PO 
  • IV
SIDE EFFECTS
All:
  • Bone marrow suppression (boxed warning for cladribine and fludarabine)

Mercaptopurine
  • Hepatotoxicity
  • GI toxicity

Cladribine
  • Nephrotoxicity (boxed warning)
  • Neurotoxicity (boxed warning)

Fludarabine
  • Neurotoxicity (boxed warning)
  • Autoimmune hemolytic anemia, autoimmune thrombocytopenia (boxed warning)
  • Bone marrow suppression (boxed warning)
  • Pulmonary toxicity
  • Secondary malignancy

Other common side effects for all medications: drowsiness, fatigue, alopecia, photosensitivity, and ulcerative stomatitis
CONTRAINDICATIONS & CAUTIONS
  • Pregnancy 
  • Breastfeeding
  • Liver and renal disease 
  • Severe infection 
  • Myelosuppression 
  • Clients taking gout medications (allopurinol / febuxostat) → increased risk of toxicity 
NURSING CONSIDERATIONS for ANTIMETABOLITES
ASSESSMENT & MONITORING
Assessment & monitoring: hydroxyurea

Assessment
  • Weight, vital signs, current symptoms 
  • Laboratory tests results: CBC, renal and hepatic function, uric acid, negative pregnancy test 
  • Diagnostic test results including peripheral blood smear; bone marrow examination results

Monitoring
  • Side effects
  • Therapeutic response: improvement in symptoms  
CLIENT EDUCATION
  • Purpose of medication: help to stop replication of cancer cells
  • Take medication at the same time each day with plenty of water
    • Take antiemetic 30 to 60 minutes before administration
    • Wear gloves; immediately wash their hands afterward administration
    • Take folic acid supplement daily 
  • Side effects
    • Nausea, vomiting, diarrhea or constipation
    • Increased their risk for infection, bleeding problems, secondary malignancy, pulmonary toxicity
    • Use reliable birth control
Transcript

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.

Sources
  1. "Focus on Nursing Pharmacology" LWW (2019)
  2. "Pharmacology" Elsevier Health Sciences (2014)
  3. "Mosby's 2021 Nursing Drug Reference" Mosby (2020)
  4. "Saunders Comprehensive Review for the NCLEX-RN Examination" Saunders (2016)
  5. "Saunders Comprehensive Review for the NCLEX-RN Examination" Saunders (2019)
  6. "Lewis's Medical-Surgical Nursing" Mosby (2019)
  7. "METHOTREXATE TREATMENT FOR YOUR HYDATIDIFORM MOLE" 2017 ()
  8. "Treating Gestational Trophoblastic Disease" 2017 ()
  9. "Molar Pregnancy" 2018 ()
  10. "Chronic Myeloid Leukemia (CML)"  (2020)