Antimetabolites: Nursing pharmacology

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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

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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.

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)" Merck Manual (2020)
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