Introduction
Cyclophosphamide is a prodrug commonly used as one of the medications within courses of chemotherapy. Since it is a prodrug, its pharmacological action unfolds after being consumed by a patient and with the immediate involvement of other biological matters that trigger its pharmacological function. Cyclophosphamide is administered to patients with cancer due to its repressing effects on tumor cells at the level of DNA. The main indications of Cyclophosphamide include lymphoma, breast cancer, ovarian cancer, retinoblastoma, disseminated neuroblastomas, and multiple sclerosis, the treatment of which is justified by the immunosuppressant action of the drug (Ogino, M. H., & Tadi, 2020). In such a manner, this medication is prescribed for different types of cancer, which is a severe disease characterized by the formation of abnormal cells in various parts of the human body. The drug treats cancer by generating “active alkylating form phosphoramide mustard,” which then can inhibit protein synthesis in the DNA and RNA of the tumor cells (Barnett et al., 2021, p. 1). Thus, Cyclophosphamide is an effective chemotherapeutic used for cancer treatment; its pharmacodynamics, pharmacokinetics, side effects, and contraindications are explored and discussed in this paper.
Causes and Various Types of Cancer
Cancer is a severe disease that includes multiple types depending on the organs or systems of the body impacted. Although this health issue is being studied in-depth, its causes remain under-researched due to the complexity of the disease. Nonetheless, the most commonly reported causes of cancer, in general, include smoking, alcohol consumption, an unhealthy diet that includes red meat and processed food, as well as products containing refined carbohydrates (Hobbs, 2022; Mariosa et al., 2019). Moreover, exposure to radioactive chemicals, physical and chemical carcinogens, excessive exposure to ultraviolet light, and contamination with “biological carcinogens like viruses, bacteria, and parasites” are reported to cause cancer (Hobbs, 2022, para. 6). Moreover, “potential causes may also be relatively ubiquitous within populations, such as air pollution or water contaminants, and may only be relevant during time windows such as childhood or young adulthood” (Mariosa et al., 2019, p. 816). Thus, a variety of factors both influenced by individuals’ lifestyles and beyond their control might be risk determinants for cancer.
Depending on the organ or system initially affected by the disease, scholars and medical professionals distinguish between several types of cancer. In particular, cancer that starts in the skin and spreads to other tissues and organs is carcinoma; cancer that initiates in bones, muscles, or blood vessels is sarcoma (Hobbs, 2022). Leukemia is a type of cancer that affects blood cells; “lymphoma and myeloma are cancers of the immune system” (Hobbs, 2022, para. 16). In addition, there exist such most prevailing types of this disease as breast cancer, lung cancer, colorectal cancer, skin cancer, ovarian cancer, and prostate cancer among many other specific types (Hobbs, 2022). Research shows that early detection utilizing screening allows for effective treatment of the disease (Barnett et al., 2021; Hobbs, 2022; Mariosa et al., 2019). Thus, it is important to identify non-pharmacological and pharmacological treatment recommendations for cancer.
Treatment Recommendations
Non-pharmacological Treatments
The treatment of cancer is manifested through a limited number of non-pharmacological methods. According to Mariosa et al. (2019), the fast development of tumor cells in cancer patients necessitates immediate and highly effective treatment, which commonly requires pharmacology. However, as for the non-pharmacological approaches to anti-cancer therapy, one might address surgery, radiation therapy, and stem-cell transplantation, as well as hormonal and biological therapy. In particular, surgeries are local interventions that allow for removing tumors from the body, thus eliminating the main cause of the cancer cell increase (Hobbs, 2022). However, surgical intrusion is not always possible and might not guarantee to heal in a long-term perspective.
Apart from surgery, radiation therapy is often used to destroy tumor cells. It is a treatment approach that entails radiation beams used for cancer cell destruction (Hobbs, 2022). As for stem-cell transplantation, this method involves the substitution of bone merrows for the following extensive chemotherapy use in leukemia patients (Hobbs, 2022). As for the pharmacological treatment, there are other drugs used to cure cancer apart from Cyclophosphamide. For example, hormonal and biological therapies are applied to stimulate the immune system and enhance protective bodily functions to suppress cancer development. In particular, nivolumab, pembrolizumab, atezolizumab, and ipilimumab are medicines that enhance the immune system for the suppression of cancer cells (Hobbs, 2022). Moreover, leuprolide, anastrozole, and letrozole are hormonal drugs used to treat hormone-related cancer (Hobbs, 2022). Similarly, targeted oncological medications, including bevacizumab, alectinib, and ibrutinib are used to kill separate cancer cells (Hobbs, 2022). Overall, according to Hobbs (2022), “different cancer treatments are often used together to remove or destroy as many cancerous cells as possible” (para. 40). Thus, it is important to review the pharmacological treatment of cancer.
Pharmacological Aspects of the Recommended Treatment
Pharmacological Class and Indication
The most common pharmacological treatment approach for cancer patients is the administration of Cyclophosphamide in the form of intravenous injections or capsules for oral intake. It is a “nitrogen mustard that exerts its anti-neoplastic effects through alkylation” (Ogino & Tadi, 2020, para. 1). This drug belongs to the pharmacological class of alkylating agents, which generate alkynes and attach them to the DNA of the cancer cells (Barnett et al., 2021). It functions by “stopping or slowing the growth or spread of certain cancer cells” (University of Illinois, 2018, para. 12). The detailed processes of pharmacodynamics and the mechanism of this drug’s action in chemotherapy are essential to consider.
Pharmacodynamics and Mechanism of Action
The pharmacodynamics of a drug implies its influence on the cured systems and disease manifestations that allows for the treatment effects of the medication. In the case of Cyclophosphamide, its pharmacodynamics involves the alkylation of the tumor cells’ DNA. Indeed, it generates “its active alkylating form phosphoramide mustard via 4-hydroxy cyclophosphamide, which can then target DNA replication in tumor cells, alongside the formation of numerous inactive or toxic metabolites” (Barnett, 2021, p. 1). The targeting of DNA is conducted through aldophosphamide’s (the product of hepatic enzyme metabolism) attachment to phosphoramide, which forms cross-linkages within DNA strands, programming them to death (Ogino & Tadi, 2020). Thus, the mechanism of Cyclophosphamide’s action in the body is a complex and multifaceted process that causes the cellular destruction of cancer.
Pharmacokinetics
In terms of its pharmacokinetics, Cyclophosphamide’s absorption, distribution, metabolism, and excretion should be reviewed. Firstly, as stated earlier this drug might be administered orally in the form of a capsule or with the help of intro-venous injections. The absorption of the drug in both administration approaches is effective and fast (Barnett et al., 2021). After rapid absorption, the drug is activated in the liver and distributed throughout the body. The metabolism of the drug involves alkylating activation, which produces such intermediates as phosphoramide mustard (which metabolizes nitrogen mustard) and acrolein (Barnett et al., 2021). These intermediates interact with the DNA as the ultimate stage of the metabolic process. The excretion of Cyclophosphamide involves the elimination of metabolites through urine and bile (Barnett et al., 2021; Ogino & Tadi, 2020). Overall, the metabolites are predominantly non-toxic, although the drug might have significant side effects addressed in the following subsection.
Side Effects and Adverse Effects
The exploration of the characteristics of a drug should be accompanied by a thorough investigation of side effects and adverse effects that might hinder the well-being of patients. In particular, Cyclophosphamide has multiple side effects that might vary from individual to individual depending on biological and environmental factors. In particular, this drug might cause nausea, diarrhea, and vomiting due to its toxic effects on the body, stomach-ace, dizziness, and decreased appetite (University of Illinois, 2018). Moreover, hair loss, rash on the skin, and sores in the mouth are the most common side effects. However, there are more severe adverse effects, such as infections, blood in urine, comorbidities affecting the lungs, heart, and liver due to the aggressive impact of the drug on the body, as well as infertility (Ogino & Tadi, 2020; University of Illinois, 2018). Moreover, “hemorrhagic cystitis is a side effect of particular clinical significance and may arise from the use of cyclophosphamide without adequate hydration or concurrent administration of mesna” (Ogino & Tadi, 2020, para. 11). Thus, it is essential to consider these side effects and educate and prepare patients for managing them properly to minimize harm.
Contraindications
When considering administering or prescribing Cyclophosphamide to patients, it is essential to consider any symptoms or concurrent health issues that might contradict the effects of the drag and cause harm to an individual’s well-being. In particular, one of the contraindications for Cyclophosphamide is allergy or sensitivity to the drug or its metabolic products (Ogino & Tadi, 2020). In addition, patients with malfunctioning the urinary system should be prohibited from this drug use due to the toxicity of excreting of metabolites; similarly, patients subject to such chemotherapeutics as busulfan or chlorambucil should not be administered Cyclophosphamide due to its incompatibility with the mentioned medications (Ogino & Tadi, 2020). Furthermore, pregnant or breastfeeding women should not undergo treatment with Cyclophosphamide since this drug might cause disabilities in a child (University of Illinois, 2018). Thus, these contraindications should be thoroughly examined and addressed at the stage of Cyclophosphamide prescription and administration.
Conclusion
In summary, Cyclophosphamide is a widely used chemotherapeutic prodrug that treats different types of cancer in a wide range of patient populations. Its pharmacodynamics involves the generation of alkylates to suppress the development of tumor cells through the direct impact on their DNA and RNA. The drug is activated in the liver and ultimately metabolizes into alkylates; the metabolites are evacuated through urine and bile. The drug causes toxic effects and is characterized by significant side effects such as vomiting, dizziness, loss of appetite, and hair loss, as well as infertility, infections, liver, bladder, and other bodily systems dysfunction. Furthermore, the contraindications of the drug include pregnancy, breastfeeding, urinary and liver diseases, as well as exposure to particular chemotherapeutics. It is essential to consider all these factors when treating patients with Cyclophosphamide.
References
Barnett, S., Errington, J., Sludden, J., Jamieson, D., Poinsignon, V., Paci, A., & Veal, G. J. (2021). Pharmacokinetics and pharmacogenetics of Cyclophosphamide in a neonate and infant childhood cancer patient population. Pharmaceuticals, 14(3), 1-11.
Hobbs, H. (2022). Cancer: Types, causes, prevention, and more.
Mariosa, D., Carreras-Torres, R., Martin, R. M., Johansson, M., & Brennan, P. (2019). Commentary: What can Mendelian randomization tell us about causes of cancer? International Journal of Epidemiology, 48(3), 816-821.
Ogino, M. H., & Tadi, P. (2020). Cyclophosphamide. StatPearls Publications.
University of Illinois. (2018). Cyclophosphamide, injectable solution.