Alkylating agents: Nursing pharmacology

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.

Then, review your client’s recent laboratory test results, including CBC, renal and liver function tests, electrolytes, and urinalysis; as well as a negative pregnancy test as needed.

Then, review any diagnostic test results, including mammogram, ultrasound, MRI, and biopsy results. Lastly, confirm the assigned Tumor, Node, Metastasis or TNM classification of the tumor and calculate the prescribed dose in mg/m2.

Next, explain to your client that cyclophosphamide will help treat their breast cancer, and that it will be administered intravenously every 21 days.

Stress the importance of increasing their fluid intake up to 2 to 3 liters per day during treatment, and to immediately report symptoms of hemorrhagic cystitis like blood in the urine.

Also, 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, as well as avoiding large crowds, people with infections, and live attenuated vaccines; and prompt them to notify their healthcare provider if they develop symptoms of infection, such as fever, chills, sore throat, or pain with urination.

In addition, stress the importance of notifying their healthcare provider if they develop symptoms of hepatotoxicity, which could manifest as lethargy, abdominal pain, nausea, vomiting, anorexia, dark-colored urine, or yellowing of the skin or eyes; as well as pulmonary toxicity, which could present as shortness of breath, cough, fatigue or fever; nephrotoxicity, which could make it more difficult to pass urine; and any symptoms of cardiotoxicity like weight gain, fatigue, swelling in the hands and feet, or trouble breathing.

Lastly, remind your client to use a reliable form of contraception during treatment.All right, when preparing to administer intravenous cyclophosphamide, ensure your client has a patent large-bore IV, port-a-cath, or PICC line in place, and that they are adequately hydrated with the ordered intravenous fluids.

Then, premedicate your client with the ordered antiemetic 30 to 60 minutes before you begin the infusion, and be sure to wear gloves and other protective clothing when handling cyclophosphamide.

While the medication infuses, instruct your client to let you know if they feel discomfort at the IV insertion site, and monitor closely for signs of extravasation, including redness, swelling, or coolness around the insertion site.

If extravasation is suspected, stop the infusion immediately, and elevate the extremity.Finally, during treatment with an alkylating agent like cyclophosphamide, be sure to closely monitor your client’s laboratory test results, as well as for the development of side effects, and evaluate for the desired therapeutic effect of an absence of symptoms associated with breast cancer.

All right, as a quick recap… Alkylating agents are medications that are mainly used to treat cancer, and 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.

These medications work by damaging the DNA of cancer cells in all phases of the cell-cycle, ultimately leading to cancer cell death.

Unfortunately, this can also affect other rapidly dividing non-cancerous cells, so alkylating agents can cause gastrointestinal toxicity, bone marrow suppression, and increase the risk of developing a secondary malignancy.

Other important side effects that can occur include hepatotoxicity, pulmonary toxicity, cardiotoxicity, and even nephrotoxicity.

When caring for a client taking an alkylating agent, nursing considerations include performing a baseline assessment, and monitoring for the development of side effects, as well as for the desired therapeutic effect.

Client teaching is focused on what to expect during treatment, as well as learning to recognize side effects and when to notify the healthcare provider.

dividing non-cancerous cells. So, alkylating agents can cause gastrointestinal, toxicity bone marrow suppression and increase the risk of developing a secondary malignancy other important side effects that can occur included pulmonary toxicity, cardiotoxicity and even nephrotoxicity, when caring for a client taking an alkylating agent, nursing considerations include performing a baseline assessment and monitoring for the development of side effects, as well as for the desired.

Therapeutic effect client teaching is focused on what to expect during treatment as well as learning to recognize side effects.

And when to notify the healthcare provider,