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Alkylating agents: Nursing Pharmacology

Notes

Notes

ALKYLATING AGENTS, PART 1/2
DRUG NAME
cyclophosphamide, ifosfamide, bendamustine
carmustine, lomustine, streptozocin
dacarbazine, temozolomide
CLASS
Nitrogen mustard derivatives
Nitrosoureas
Triazenes
MECHANISM of ACTION
DNA damage in all phases of cell-cycle → cancer cell death
  1. Attach alkyl groups to DNA bases → repair enzymes attempt to replace alkylated bases → DNA fragmentation 
  2. Cause two DNA bases to link together → formation of cross-bridges → DNA cross-linking → inhibition of essential cell processes (e.g., replication)
INDICATIONS
Cancer treatment
  1. Hematologic malignancies (e.g., leukemia, lymphoma, multiple myeloma)
  2. Solid tumours (e.g., breast, ovarian, uterus, lung, bladder cancers)
ROUTE(S) of ADMINISTRATION
  • IV
  • IV
  • PO
  • IV
SIDE EFFECTS
Common side effects for all medications:
  • Myelosuppression 
  • Tumor lysis syndrome
  • Gastrointestinal disturbances 
  • Infertility 
  • Alopecia
Cyclophosphamide:
  • Cardiotoxicity
  • Pulmonary toxicity
  • Secondary malignancy
  • Hemorrhagic cystitis

Ifosfamide:
  • Myelotoxicity (boxed warning)
    Nephrotoxicity (boxed warning)
    Hemorrhagic cystitis (boxed warning)

Bendamustine:
  • Hepatotoxicity
Carmustine
  • Pulmonary toxicity (boxed warning)
  • Myelotoxicity (boxed warning)
  • New malignancy
  • Hepatotoxicity
  • Nephrotoxicity

Lomustine:
  • New malignancy
  • Myelotoxicity (boxed warning)
  • Hepatotoxicity
  • Nephrotoxicity
  • Pulmonary toxicity

Streptozocin:
  • Hepatotoxicity (boxed warning) 
  • New malignancy (boxed warning)
  • Nephrotoxicity (boxed warning)
Dacarbazine:
  • Myelotoxicity (boxed warning)
  • Hepatotoxicity (boxed warning)
  • New malignancy (boxed warning)

Temozolomide:
  • Myelotoxicity
  • New malignancy

CONTRA-INDICATIONS & CAUTIONS
  • Pregnancy 
  • Breastfeeding
  • Liver disease
  • Renal disease
  • Alcohol use (disulfiram-like reactions)  
  • Foods that contain tyramine (e.g., chocolate, cheese, wine) → tyramine-induced hypertensive crisis
ALKYLATING AGENTS, PART 2/2
DRUG NAME
busulfan
procarbazine
CLASS
Other alkylating drugs
Other alkylating drugs
MECHANISM of ACTION
DNA damage in all phases of cell-cycle → cancer cell death
  1. Attach alkyl groups to DNA bases → repair enzymes attempt to replace alkylated bases → DNA fragmentation 
  2. Cause two DNA bases to link together → formation of cross-bridges → DNA cross-linking → inhibition of essential cell processes (e.g., replication)
INDICATIONS
Cancer treatment
  1. Hematologic malignancies (e.g., leukemia, lymphoma, multiple myeloma)
  2. Solid tumours (e.g., breast, ovarian, uterus, lung, bladder cancers)
ROUTE(S) of ADMINISTRATION
  • PO
  • IV
  • PO
SIDE EFFECTS
Common side effects for all medications:
  • Myelosuppression 
  • Tumor lysis syndrome
  • Gastrointestinal disturbances
  • Infertility
  • Alopecia
  • Myelotoxicity (boxed warning)
    Pulmonary toxicity
  • Neurotoxicity (seizures)
  • Myelotoxicity
CONTRAINDICATIONS & CAUTIONS
  • Pregnancy 
  • Breastfeeding
  • Liver disease
  • Renal disease
  • Alcohol use (disulfiram-like reactions)  
  • Foods that contain tyramine (e.g., chocolate, cheese, wine) → tyramine-induced hypertensive crisis
NURSING CONSIDERATIONS for
ALKYLATING AGENTS
ASSESSMENT & MONITORING
Assessment
  • Weight 
  • Vital signs 
  • Current symptoms: hard, immovable lump in the breast or underarm, nipple discharge, pain, breast or nipple skin changes 
  • Laboratory test results: CBC, renal and hepatic function, electrolytes, urinalysis; negative pregnancy test
  • Diagnostic test results: mammogram, ultrasound, MRI, biopsy
  • TNM classification

Administration
  • Ensure patent large-bore IV, port-a-cath, PICC line
  • Hydrate with IV fluids
  • Premedicate with antiemetic 30 to 60 minutes 
  • Wear gloves and protective clothing when handling medication

Monitoring
  • Extravasation 
  • Side effects
  • Evaluate for the desired therapeutic effect: absence of symptoms associated with breast cancer 
CLIENT EDUCATION
  • Purpose of the medication: treat breast cancer 
  • Administered IV 
  • Report symptoms of side effects 
    • Hemorrhagic cystitis
      • Hematuria
      • Increase fluid intake up to 2–3 liters per day
    • Increased risk for infection
      • Fever, chills, sore throat, pain with urination
      • Frequent hand hygiene, avoid crowds and contact with people with known infections; avoid live attenuated vaccines
    • Hepatotoxicity
      • Lethargy, abdominal pain, nausea, vomiting, anorexia, dark-colored urine, yellowing of the eyes or skin
    • Nephrotoxicity
Transcript

Alkylating agents are medications that are mainly used to treat cancer. They are effective against hematologic malignancies, such as leukemia, lymphoma, and multiple myeloma, as well as solid tumors, like breast, ovarian, uterus, lung, and bladder cancer.

The most commonly used alkylating agents are nitrogen mustards like cyclophosphamide, bendamustine, and ifosfamide; nitrosoureas like carmustine, lomustine, and streptozocin; triazenes, such as dacarbazine and temozolomide; and other alkylating agents, including busulfan and procarbazine.

Alkylating agents are cell-cycle phase nonspecific, which means they work by causing damage to the DNA of cancer cells in all phases of the cell-cycle, ultimately leading to cancer cell death. There are two primary ways they do this. First, they can attach an alkyl group to one of the DNA bases of cancer cells. Repair enzymes recognize there’s something wrong, so they jump in to replace the alkylated bases and cause DNA fragmentation, which eventually results in DNA damage and cancer cell death.

The second mechanism is the crosslinking of DNA, which means the alkylating agent links two DNA bases together, forming cross-bridges. Cross-linking prevents DNA from being separated for essential cell processes, like replication or transcription, eventually resulting in cancer cell death and stopping the multiplication of cancer cells.

In terms of side effects, all alkylating agents can cause gastrointestinal toxicity, which can manifest as anorexia, vomiting, stomatitis or diarrhea; and tumor lysis syndrome, which is when a lot of cancer cells are killed rapidly and that can cause metabolic disturbances. There’s also a risk of damaging other rapidly- dividing, non-cancerous cells, like hair cells, skin cells, and the germ cells in the gonads, which can cause alopecia, rashes and infertility.

All alkylating agents can also cause bone marrow suppression, leading to decreased platelets and increased risk of bleeding, decreased red blood cells, causing anemia, and decreased white blood cells, increasing the risk of infections. This is actually a boxed warning for ifosfamide, carmustine, lomustine, dacarbazine and busulfan. The most dangerous side effect is the risk of developing a new malignancy, and the risk is higher after prolonged treatment with cyclophosphamide, carmustine, lomustine, temozolomide, while for dacarbazine and streptozocin, it’s actually a boxed warning.

Now, these medications also come with specific organ system toxicities. For example, pulmonary toxicity, which can manifest as pulmonary fibrosis or pneumonitis, can occur with cyclophosphamide, lomustine and busulfan, and it’s a boxed warning for ifosfamide and carmustine. Of these, cyclophosphamide is the most cardiotoxic medication. Nephrotoxicity can occur during treatment with alkylating agents, and it’s a boxed warning for streptozocin.

Urotoxicity, which can manifest as hemorrhagic cystitis and hematuria are important side effects with cyclophosphamide and it's a boxed warning for ifosfamide. Some alkylating agents, such as ifosfamide, dacarbazine, temozolomide, busulfan, and procarbazine, are also neurotoxic, and this comes as a boxed warning for ifosfamide. Hepatotoxicity is also a boxed warning for dacarbazine and streptozocin, and a side effect of cyclophosphamide and bendamustine.

As far as contraindications go, alkylating agents should not be used during pregnancy and breastfeeding because they are teratogens, meaning they disrupt fetal development, which can lead to birth defects. They should also be used with caution in clients with liver and renal disease.

In addition, alcohol consumption should be avoided during treatment with procarbazine, because these two substances together can cause disulfiram-like reactions, sometimes called hangover-like symptoms, such as nausea, vomiting, flushing, dizziness, and headache. During procarbazine treatment, certain foods that contain the molecule tyramine should be avoided, such as chocolate, cheese, and wine, because that can cause a tyramine-induced hypertensive crisis.

All right, when a client with breast cancer is prescribed an alkylating agent like cyclophosphamide as part of their chemotherapy regimen, first perform a baseline assessment, including weight, vital signs, and current symptoms, such as the presence of a hard, immovable lump in the breast or underarm, as well as nipple discharge, pain, and any skin changes on the breast or nipple.