Antineoplastic Antibiotics

Streptomyces produces antineoplastic antibiotics. Actinomycin D (dactinomycin), doxorubicin, mitoxantrone, and bleomycin are examples of important drugs in this class. Daunorubicin, mithramycin, and mitomycin are less commonly used drugs.

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Antineoplastic Meaning

Antineoplastic antibiotic, also known as anticancer antibiotics or antitumor antibiotics, any anticancer drug that interferes with DNA synthesis and replication by inserting into DNA or donating electrons, which further results in the production of highly reactive oxygen compounds (superoxide) that cause DNA strand breakage. These antibiotics are almost entirely administered intravenously for the treatment of lymphoma and leukaemia, nephroblastoma (Wilm tumour), sarcoma, and cancers of the testicle, breast, thyroid, lung, and stomach.

Doxorubicin, daunorubicin, bleomycin, mitomycin, as well as dactinomycin are examples of antineoplastic antibiotics derived from Streptomyces bacteria. While these drugs may have antibacterial activity, these drugs are generally too dangerous and toxic to be used in this manner. Antineoplastic antibiotics cause blood cell damage, hair loss, and other toxicities common to antimetabolites and alkylating agents, as well as severe cardiac or lung toxicity. The effects are proportional to the dose and duration of treatment.

Pharmacological Management of Side Effects of Cancer Treatments

The use of drug interventions to manage antineoplastic drug side effects is critical to the success of oncology care. Maintaining chemotherapy dosing as well as cycle timing as close to regimen specificity is ideal. In many cases, careful pharmacological interventions that improve an individual's tolerance to cancer treatments and improve quality of life during cancer care are the only way to manage the rigours of the prescribed antineoplastic therapies. However, using additional drugs to manage the side effects of cancer treatment has implications and increases the risk of further drug interactions. Many of the medications used to manage the most common toxicities of antineoplastic therapies alter body functions further and can perpetuate a decline in functioning.

Many of the medications used to manage the most common toxicities of antineoplastic therapies alter body functions further and can perpetuate a decline in functioning.

Nausea/vomiting (N/V) is a common side effect of many antineoplastic drug therapies. The key to treating N/V is prevention, and many therapeutic solutions have emerged in recent years. Unfortunately, current pharmacological options have side effects like headache and constipation. Furthermore, they are frequently co-prescribed with corticosteroids for maximum benefit, which can potentiate additional negative effects. Medication used to treat side effects can sometimes be so effective that they cause the opposite reaction. A patient suffering from diarrhoea, for example, may be given multiple anti-diarrhoea medications to prevent dehydration and electrolyte imbalance, which can lead to severe constipation.

What are the Side Effects of Antineoplastic Agents?

• Chemotherapy frequently causes side effects.

• Infections and anaemia are more likely to develop when blood counts are low.

• Weakness.

• Soreness in the mouth.

• Vomiting and nausea.

• Appetite loss.

• Diarrhoea or constipation

• Hair thinning.

• Skin reactions or changes

The first Streptomyces antibiotic isolated was actinomycin A, which was followed by related antibiotics such as actinomycin D. Actinomycin D binds to double-stranded DNA and inhibits RNA polymerase activity, preventing DNA transcription. Actinomycin D is a cell-cycle nonspecific antibiotic that is administered intravenously but does not cross the blood-brain barrier. Resistance may develop as a result of decreased drug uptake by cells. It is occasionally used as a substitute for doxorubicin in dogs with questionable cardiac function or in dogs who have received more than the cumulative cardiotoxic dose of doxorubicin.

Anthracycline antibiotics, particularly doxorubicin, have emerged as important anticancer agents. These drugs intercalate and bind to DNA between adjacent strand base pairs. The DNA helix uncoils, destroying the DNA template and inhibiting RNA and DNA polymerases. DNA severing is thought to be mediated by the enzyme topoisomerase II or by the generation of free radicals. Anthracycline antibiotic intracellular interactions result in the formation of semiquinone radical intermediates capable of producing hydrogen peroxide and hydroxyl radicals.

Because of the damage associated with radical formation, these drugs are thought to have their greatest effect during the S phase of the cell cycle. The anthracycline antibiotics are administered intravenously; if administered perivascularly, they are severe vesicants and can cause severely delayed phlebitis. Dexrazoxane, a free radical scavenger, may limit the extent of tissue damage seen with this drug extravasation. In the liver, anthracycline antibiotics are metabolised into a variety of less active and inactive products.

Doxorubicin toxicity can manifest as a number of acute and delayed reactions. Hypersensitivity reactions (due to nonspecific histamine release), extravasation injury, or transient cardiac arrhythmias are examples of acute effects. Delayed toxicity can be severe, with the most serious issue in dogs being cumulative, dose-related cardiac toxicity caused by drug binding to cardiac DNA and free radical damage to myocardial membranes. A nonspecific decrease in cardiac fibrils occurs, resulting in congestive heart failure that is resistant to digitalis.

Because doxorubicin's cardiotoxic effects are related to peak plasma concentrations (rather than the area under the curve), slow IV administration over 15–30 minutes is recommended to help reduce cardiac injury. Doxorubicin-induced myocardial damage can also be avoided by taking dexrazoxane at ten times the doxorubicin dose. Cumulative doxorubicin doses in cats can cause nephrotoxicity and should be avoided or used cautiously in cats with preexisting renal insufficiency.