Pharm. D.
Anti-cancer drugs target to kill the cancer cells, leading to apoptosis and arresting their progress. There are many types of anti-cancer drugs. In this article, we will focus on alkylating agents.
The alkylating agents bind to nucleophile groups of the cell, forming a covalent bond with them. They destroy the normal base pairing of DNA and break its strands. The purpose of these drugs is to kill the rapidly dividing cancer cells.
Examples of alkylating agents include:
Here we will review the mechanism of action, side effects, and drug interactions of alkylating agents.
First, let’s take a few minutes to learn more about their indications.
Alkylating agents are combined with other anticancer drugs to kill cancerous cells as they cannot differentiate between cycling and resting cells. But mostly, they affect the rapidly dividing cells.
With these indications in mind, you can learn about the mechanism of action of the alkylating agents and how they kill the cancerous cells in chemotherapy.
If you are unfamiliar with the cell cycle, it is better to take a few moments to learn about it.
There are four stages of the cell cycle:
In the cell cycle, the cell replicates to produce its new copies. The cell duplicates in the G1 phase, and the DNA replicates in the S phase. In the G2 phase, the cell prepares itself for division, and in the M phase, cell separation takes place, resulting in two identical daughter cells.
The alkylating agents are not cell cycle-specific. But they are most active in the interphase- the phase in which the chromosomes can not distinguish from each other.
The alkylating agents break down spontaneously or after cell metabolism and produce reactive molecular species that attack the nucleophile groups on the DNA bases and alkylate them. That leads to an impaired base pairing of DNA and finally causes breakage of the DNA strands. It is a potent cell cycle checkpoints activator and activates cell signalling pathways that can cause apoptosis.
The side effects of alkylating agents are:
The major drawback of alkylating agents is that it targets all the cells, irrespective of whether they are normal or cancerous. It leads to increased adverse effects that can cause leukemia because it also targets the normal cells of bone marrow, which produces new blood cells, eventually resulting in an abnormal blood cell count.
The risk of leukemia from alkylating agents is dependent on dose. Lower doses pose a little risk, while higher doses pose a greater risk.
When we talk about the clinical pharmacology of alkylating agents, we need to keep these things in mind:
Melphalan may cause a decrease in renal function and increased blood urea. Administer it with caution in renal compromised patients and monitor their kidney functions daily.
Procarbazine may cause high blood pressure with tyrosine-rich foods, such as cheese, chicken, peanuts, milk, and others.
Cisplatin can cause diuresis. Therefore you must monitor serum potassium and magnesium in patients receiving it.
Oxaliplatin can cause anemia. Therefore keep an eye on the blood counts of the patients receiving it.
Procarbazine can cause disulfiram-like effects with alcohol. Ask the patient to avoid alcohol intake while on its chemotherapy.
Cisplatin and cyclophosphamide can lower the platelet count and increase the risk of bleeding. Therefore administer it with caution, especially if the patient is already receiving anticoagulant drugs.
Cisplatin, along with amiodarone, may cause arrhythmias. Monitor electrolytes if you are administering these two drugs together.
The use of dacarbazine along with nalidixic acid may cause severe drug interaction. The combination can cause bleeding, bruising, nausea and weakness.
Avoid chlorambucil if the patient has infections, as it induces myelosuppression.
Oxaliplatin can cause pulmonary fibrosis. Therefore exercise caution while administering it to pulmonary compromised patients.
Alkylating agents continue to play an essential clinical role in cancer treatment. Knowing how they work, their side effects and drug interactions, and how these facts implicate therapeutic matters is an absolute must for every nurse.
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