Daunorubicin is a drug in the cytostatic and anthracycline drug class. The drug is used as a cytostatic agent.
What is daunorubicin?
Daunorubicin is available by prescription and is used to treat a variety of cancers. For this purpose, the drug is infused intravenously. Daunorubicin is both a glycoside and an antibiotic. It comes from the group of anthracyclines. Anthracyclines are antibiotics used in chemotherapy as cytostatics against various malignant cancers. The antibiotic daunorubicin is produced by the bacterial species Streptomyces peuceticus and Streptomyces coeruleorubidus. Chemically, the basic molecular structure of the drug consists of four benzene rings arranged in a row. Accordingly, daunorubicin belongs to the group of aromatic hydrocarbon compounds or aromatics. At room temperature, daunorubicin is in solid form. The melting point is 208 °Celsius, and solubility in water is poor. Daunorubicin is available by prescription and is used to treat various cancers. For this purpose, the drug is infused intravenously. Unlike some other cytostatic drugs, daunorubicin is not used as an immunosuppressant drug in autoimmune diseases.
Pharmacologic action
Daunorubicin is a so-called DNA intercalator. The planar structure of the drug elicits intercalation in the nucleic bases of DNA. The term intercalation refers to the reversible intercalation of atoms, molecules, ions or other chemical compounds into DNA. In the case of daunorubicin, the drug intercalates into the DNA. The process of intercalation disrupts the replication of DNA. The transcription of the DNA is also impaired. When replication is disrupted, mitosis cannot occur. In mitosis, the nucleus divides and the DNA is split. Without mitosis, cell division cannot occur, or the cells that develop when mitosis is impaired die programmed cell death (apoptosis). Since cancer cells divide particularly often and particularly quickly, they are most affected by drugs that interfere with mitosis. However, many of the side effects occur because the body’s cells as a whole are inhibited in their growth by drugs of this type. In addition to replication and transcription, RNA synthesis with polypeptide formation is also affected by the action of daunorubicin. In addition, daunorubicin has an inhibitory effect on topoisomerase II. This enzyme also plays an important role in cell division. However, daunorubicin has a third mechanism of action. After absorption of daunorubicin, the drug is activated. In a redox reaction, an intermediate is formed that acts in a similar way to free radicals. It transfers electrons to molecular oxygen. This in turn is then unconverted to hydroxyl and superoxide radicals. Both forms of radicals have a cytotoxic effect. They damage DNA, preferentially the strand breaks of DNA.
Medical application and use
Daunorubicin is a cytostatic drug used to treat malignant cancers. In adults, the drug is administered in the treatment of acute myeloid and acute lymphoblastic leukemia. In acute myeloid leukemia (AML), the hematopoietic system is affected. There is a massive proliferation of immature precursors of blood cells in the bone marrow. In acute lymphoblastic leukemia (ALL), the lymphocyte precursor cells degenerate. The therapy of both forms of leukemia is almost always carried out in combination with other cytostatic drugs. Daunorubicin is also used in children to treat acute myeloid leukemia and to treat acute lymphoblastic leukemia. Daunorubicin is also combined with other cytostatic drugs here. In acute lymphoblastic leukemia, daunorubicin is administered in the so-called induction phase, that is, at the beginning of treatment.
Risks and side effects
The side effects of daunorubicin are due to its cytotoxic and growth-inhibiting effects. In general, the tissues most affected are those that have a high rate of cell division and/or growth. These include, for example, the mucous membranes, hair and bone marrow. In the gastrointestinal tract, daunorubicin may cause mucosal damage. The damage may be minor, but ulcers may develop.This results in pain in the mouth or abdomen, depending on the localization. Nausea may also develop as a result of the mucosal damage. In some cases, patients have to vomit several times a day. This is due on the one hand to the mucosal damage and on the other hand directly to daunorubicin. The mucosal damage can be so severe that bowel function is impaired. As a result, diarrhea requiring treatment may occur. Daunorubicin also damages hematopoiesis in the bone marrow. This results in a deficiency of leukocytes (leukopenia), platelets (thrombocytopenia) and erythrocytes (anemia). The nadir of hematopoiesis is reached eight to ten days after daunorubicin administration. About three weeks after administration, the hematopoietic system has usually recovered. As a result of the lack of white blood cells, infections occur more frequently during and after therapy with daunorubicin. These are mainly infections with bacteria and fungi. These can be life-threatening. Thrombocytopenia increases the risk of bleeding in patients. A typical side effect of daunorubicin therapy is hair loss. Hair growth may stop or complete hair loss may occur. This side effect of daunorubicin is usually fully reversible. In contrast, the cardiotoxic effect of daunorubicin may leave irreversible damage. Acute cardiotoxicity results in arrhythmias, angina, and inflammation of the heart muscle. The late type often manifests weeks, months, or years after daunorubicin administration. Patients develop pulmonary edema or heart failure. Cardiomyopathy may be severe enough to require heart transplantation. Because of the serious side effects, daunorubicin should not be given during pregnancy or while breastfeeding. Severe heart disease is also among the contraindications.
