Adriamycin - efficacy and possible adverse effects

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Abstract

Adriamycin (doxorubicin) is a chemical substance in the anthracycline class with a wide range of applications in oncology and hematology. The mechanism of action of Adriamycin is related to formation of irregular bonds between nucleobases of DNA and inhibition of key enzymes of DNA synthesis - topoisomerase I and II as well as to formation of free radicals damaging DNA.

A major limitation in the drug use is associated with its adverse effects such as cardiotoxicity and hepatotoxicity.

The mechanism of myocardial injury by Adriamycin is linked to an increase in oxidative stress associated with impaired mitochondrial function and structure.

Cardiotoxicity of anthracyclines is classified as: acute, chronic or late (delayed).

Hepatotoxicity of Adriamycin as a damage of the liver is associated with a dysfunction of this organ. Adriamycin studies have shown increased level of transaminase present in 40% of patients treated with Adriamycin. The state was transient and asymptomatic, returning to the initial level even when treatment continued.

Knowledge of cancer diseases contributed to a successive creation of two improved forms of Adriamycin (doxorubicin) – nonpegylated and pegylated formulas of the drug.

The mechanism of anticancer effects of liposomal Adriamycin is similar to the mechanism of conventional Adriamycin, but placement of the molecules of active substance in liposomes has significant influence on the distribution of the drug.

In order to increase the distribution of the drug, a special form of liposomal Adriamycin has been created by covering the surface of the liposomes with a hydrophilic polymer - (MPEG). This process, known as pegylation, decreases the interactions between the lipid bilayer membrane and the plasma components. Pegylated form of the drug is associated with a higher incidence of acute complications.

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