General characteristics and main groups
These medicinal products are produced by soil fungi of the genus Streptomyces. In modern clinical practice, they are divided into several key groups:
- Anthracyclines (including doxorubicin and daunorubicin);
- Bleomycin — a glycopeptide complex;
- Mitomycin;
- Dactinomycin (actinomycin D) — historically the first antibiotic introduced into the arsenal of antitumor chemotherapy.
Most drugs in this category are administered exclusively parenterally (most often intravenously) because they are destroyed by digestive enzymes or are not properly absorbed in the gastrointestinal tract. An important general pharmacokinetic feature is the inability to cross the blood-brain barrier.
Dactinomycin: mechanism of action
Dactinomycin is used for such pathologies as Wilms tumor, choriocarcinoma, and rhabdomyosarcoma.
Mechanism of action:
- Intercalation: the molecule inserts into the DNA helix strictly between guanine-cytosine base pairs, forming a stable complex.
- Inhibition of RNA synthesis: the drug inhibits DNA-dependent RNA polymerase, which halts transcription.
- Radicals: free radicals may be released during decomposition, damaging the structure of nucleic acids.
The drug is excreted via the gastrointestinal tract with bile. The main risks include immunosuppression, myelosuppression, and severe local toxicity: leakage of the solution under the skin causes severe tissue necrosis.
Anthracycline antibiotics: doxorubicin and daunorubicin
Anthracyclines are structurally related compounds, where doxorubicin is a hydroxylated analogue of daunorubicin. They exhibit four pathways of cytotoxic action: DNA intercalation, inhibition of the vital enzyme topoisomerase II, membrane toxicity, and generation of oxidative stress.
- Indications: Doxorubicin is prescribed for a wide range of solid tumors (sarcomas, breast cancer) and hemoblastoses. Daunorubicin is used primarily for acute leukemias.
- Side effects: Myelosuppression is the dose-limiting factor. The most dangerous complication is cardiotoxicity due to lipid peroxidation in the myocardium. Dexrazoxane and liposomal formulations are used for prevention. A characteristic external sign of administration is the red coloration of urine and blood vessels.
Bleomycin: phase specificity and organotropism
Bleomycin is a mixture of glycopeptides that acts phase-specifically, arresting cells predominantly in the G2 phase of the cycle.
The drug interacts with ferrous iron and DNA to form a ternary complex that generates reactive oxygen species and causes DNA strand breaks.
- Organotropism: In the liver and spleen, the drug is rapidly degraded by the enzyme hydrolase, but in the skin and lungs, the activity of this enzyme is low. Consequently, high concentrations of the active substance accumulate in lung tissue, which can lead to severe and potentially fatal fibrosis ("bleomycin lung").
- Distinguishing feature: Unlike most other cytostatics, bleomycin does not cause bone marrow suppression.
Briefly: answers to topical questions
What side effects are characteristic of dactinomycin?
Dactinomycin is characterized by the following side effects:
- Bone marrow suppression.
- Immunosuppression.
- Local toxicity: tissue necrosis upon extravasation (drug leakage outside the vein).
How are anthracycline antibiotics eliminated from the body?
Anthracycline antibiotics are eliminated:
- with bile through the intestines;
- in the urine.
The dark red color of the drug may cause urine to turn brown.
Anthracyclines arrest DNA, destroy cells via radicals, break strands via topoisomerase, and color urine red.
Class and exam questions
Why are antitumor antibiotics administered exclusively intravenously?
Most drugs in this group, such as anthracyclines and dactinomycin, are completely destroyed by gastrointestinal enzymes or do not cross the gut wall into the bloodstream at therapeutic doses.
What is the cardiotoxicity of anthracyclines and how can it be prevented?
Cardiotoxicity is associated with the release of free radicals and lipid peroxidation in cardiomyocytes. Dexrazoxane, which binds metal ions, and special liposomal formulations are used for prevention.
What specific complication is characteristic of bleomycin?
The main specific complication is the development of pulmonary fibrosis ("bleomycin lung"), arising from low activity of protective hydrolases in lung tissue.
Does myelosuppression develop with the use of bleomycin?
No, bone marrow suppression (myelosuppression) is not characteristic of bleomycin, which distinguishes it favorably from most other antitumor antibiotics.
What else to study on this topic
- Mechanisms of tumor cell resistance (P-glycoprotein and glutathione transferases)
- The role of topoisomerase II in the cytotoxic effect of anthracyclines
- Pharmacogenetics and tissue hydrolase activity during bleomycin therapy
- Comparative spectrum of indications for doxorubicin and daunorubicin
- Prevention and management of cytostatic extravasation
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