Introduction
Etoposide is an (anti-cancer medication) antineoplastic agent that is an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It blocks DNA (deoxyribonucleic acid) topoisomerase II, eventually deters DNA synthesis. Etoposide is phase-specific based on the cell cycle, affecting especially the S and G2 phases (phases of the cell cycle). Two distinct dose-dependent reactions are seen where elevated concentrations of more than ten µg/mL cause lysis of cells joining mitosis, whereas at low concentrations of 0.3 to 10 µg/mL leads to cells are blocked from joining prophase. The etoposide's inhibition of the DNA topoisomerase II enzyme prevents DNA re-ligation. This results in significant mistakes in DNA synthesis during the premitotic stage of cell division, which may cause the cancer cell to undergo apoptosis. In addition, Etoposide has anti-tumor action as it inhibits the topoisomerase II alpha isoform. Although the medication can also inhibit the beta isoform, doing so is not thought to have anti-tumor effects. Instead, it is linked to the cancer-causing impact.
Patients with advanced testicular germ cell cancers are treated with etoposide-based combination chemotherapy to cure them. Leukopenia (up to 91%), baldness (up to 66%), and nausea and vomiting (up to 43%) are common adverse effects. Only one to two percent of people experience hypotension as a side effect of cardiovascular medications.
Thyroid dysfunction is not a known adverse effect of etoposide. After starting chemotherapy using an etoposide basis, we saw a case of bradycardia and a shortening of the QT interval. A 37-year-old man was admitted for cycle 2/4 of etoposide-based chemotherapy after being diagnosed with a stage IV mixed germ cell tumor of the right testis, retroperitoneal lymphadenopathy, and lung masses. He also complained of significant bradycardia and chest pain. The patient did not report feeling faint or dizzy. Exceptional vital indicators included a blood pressure of 120/70 mm Hg.
What Are the Drugs That Cause Cardiotoxicity?
Cardiotoxicity Potential of Chemotherapeutic Agents
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Anthracyclines (Anthraquinones):
Congestive heart failure or left ventricular dysfunction due to free radical production.
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DoxorubicinDaunorubicin.
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Epirubicin.
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Idarubicin.
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Mitoxantrone.
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Alkylating Agents
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Busulfan: Associated with endomyocardial fibrosis and cardiac tamponade.
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Cisplatin: Cause ischemia and hypertension. With CHF, the risk is increased in the elderly.
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Cyclophosphamide: Associated with pericarditis or myocarditis and rare incidence of hemorrhagic myocarditis, more common with high dosage.
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Ifosfamide.
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Mitomycin.
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Antimetabolites
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Capecitabine: Associated with ischemia, and the mechanism is potentially vasospasm or thrombosis.
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Cytarabine: Associated with pericarditis and rare cases of cardiomyopathy after high-dose therapy in combination with cyclophosphamide.
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Fluorouracil: Associated with ischemia, vasospasm, and cardiogenic shock.
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Antimicrotubules
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Paclitaxel: Sinus bradycardia, AV block, and ventricular tachycardia. Hypotension has often seen with hypersensitivity.
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Vinca alkaloids: Ischemia with increased risk with CAD coronary artery diseases.
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Biological Agents
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Monoclonal antibodies.
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Alemtuzumab.
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Bevacizumab: Severe hypertension (>200/110 mm Hg) seen in seven percentof patients in a recent trial.
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Cetuximab: Hypotension with severe infusion reactions like bronchospasm, stridor, urticaria.
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Rituximab: Hypotension as a side effect.
What are Anthracyclines, and How Does It Affect the Cardiac System?
Doxorubicin and idarubicin are examples of the major class of chemotherapeutic drugs known as anthracyclines. Unfortunately, cumulative dose-dependent cardiotoxicity that might result in irreparable heart failure limits their effectiveness in treating cancer. Based on the agent's impact on cardiomyocytes, chemotherapeutic cardiotoxicity can be divided into type 1 and type 2.
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Type I cardiotoxicity is irreversible because it results from the destruction of cardiomyocytes through necrosis or apoptosis.
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Type II cardiotoxicity may be reversible since it results from malfunctioning the cardiomyocytes rather than cell death. However, the anthracyclines cause long-term cardiotoxicity, including cardiomyocyte loss, and are classified as type I toxicity.
What are Alkylators, and How Does It Affect the Cardiac System?
The alkylators, a class of chemotherapeutic drugs initially used to treat leukemia, are another widely utilized group. A few reports of pericardial and endomyocardial fibrosis develop four to nine years after busulfan treatment. However, these instances typically involved cumulative dosages above 600 mg. In combination with chemotherapy, cyclophosphamide has been utilized to treat a variety of solid tumors and lymphomas. Low doses of cyclophosphamide are generally well tolerated, but high-dose regimens, such as those used in bone marrow transplants, can have several side effects. However, the strongest predictor of acute cardiotoxicity appears to be the entire dose of a single course rather than the cumulative dose. Mediastinal radiation therapy and prior anthracycline therapy have also been suggested as contributory factors. Chest discomfort, palpitations, and increased cardiac enzymes suggestive of myocardial infarction are acute clinical symptoms connected to cisplatin infusion (MI). A small percentage of patients who received cisplatin and cyclophosphamide also suffered heart failure; the risk was highest in older patients who had previously had mediastinal irradiation. Cisplatin is exceptional in that it can result in long-term cardiovascular side effects such as hypertension, left ventricular hypertrophy, myocardial ischemia, and myocardial infarction up to 10 to 20 years after metastatic testicular cancer has been cured. Up to 35 % of cisplatin-treated patients may have nephrotoxicity, which can result in severe hypomagnesemia and hypokalemia and, in turn, contribute to cardiac arrhythmias.
How Do Antimetabolites Affect Cardiac Tissue?
The chemotherapeutic 5-fluorouracil (5-FU) is frequently employed in numerous solid tumor therapy protocols. The ischemia syndrome, which clinically ranges from angina pectoris to severe myocardial infarction MI, is the most frequently mentioned cardiotoxic consequence. The ischemia is typically reversible when the 5-FU is stopped and anti-ischemic medical therapy is started.
Ischemia can happen in people who don't have coronary artery disease (incidence: 1.1 %), although it happens more frequently in people with coronary artery disease CAD (4.5 %). Capecitabine, now used to treat gastrointestinal and breast malignancies, is considered less hazardous than 5-FU. Angina or MI, arrhythmias, abnormalities in the ECG, and cardiomyopathy are other cardiotoxic side effects linked to capecitabine that have been recorded.
Conclusion
Numerous chemotherapeutic drugs produce cardiotoxicity, necessitating strict monitoring and counseling throughout usage. The pharmacist can be quite helpful in ensuring that orders are accurate because many of these medications contain dosing-adjustment parameters. By being aware of the symptoms and signs of HF and encouraging the patient to visit the doctor and undertake the necessary testing, the pharmacist can assist in identifying the presence of cardiotoxicity.
