Alkylating agents: Nursing pharmacology

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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

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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.

Summary

Alkylating agents are antineoplastic drugs that work by inhibiting the transcription of DNA to RN by alkylation. Alkylation is the process of adding an alkyl group ( �CH3) to DNA. This process prevents the DNA from being used in protein synthesis and the production of new cells, including cancer cells. Some common alkylating agents include cyclophosphamide, chlorambucil, and melphalan.