Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epirubicin (4'-epi-doxorubicin) is a new anthracycline cytostatic, which was synthesized in an effort to find an agent with an improved therapeutic effect on human malignant tumours combined with reduced myocardial toxicity. Animal experiments have previously shown that the parent drug doxorubicin, besides being a myocardial toxin, may cause nerve cell lesions both in the central and the peripheral nervous system. Intravenously (i.v.) injected doxorubicin passes into regions of the nervous system located outside the blood-brain barrier (BBB); the drug accumulates in the nucleus of neurons and causes cell degeneration. This investigation was performed to establish whether epirubicin, given as a single i.v. injection in the mouse, could enter the central nervous system (CNS) and cause neurotoxic effects. Epirubicin was found to emit a primary orange fluorescence in thin frozen sections. Detectable amounts of epirubicin could not be seen in regions protected by the BBB. The choroid plexus and all the circumventricular brain regions with the exception of the subcommissural organ showed the presence of the drug in the parenchyma and a marked accumulation in cell nuclei. Severe cellular changes were found in these regions by light and electron microscopy and the alterations were most marked in mice with the longest survival period (45 days). The animals also developed a progressive sensory polyneuropathy and appeared lethargic. Epirubicin given as a single i.v. injection in the mouse will thus spread into brain regions lacking a BBB where it produces toxic lesions in the same way as previously reported for the parent compound, doxorubicin.
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PMID:Distribution and toxic effects of intravenously injected epirubicin on the central nervous system of the mouse. 270 39

Epirubicin is a stereoisomer of doxorubicin that is widely used in human oncology. The purpose of this study was to evaluate the toxicity associated with epirubicin administration in dogs. Three hundred and fifteen treatments were administered to 139 dogs. Patients received between one and seven doses. One hundred and sixteen treatments were associated with toxicity in 81 patients (50 episodes of lethargy, 49 of diarrhoea, 42 of vomiting, 40 of anorexia, 2 hypersensitivity reactions and 2 suspected extravasations). Thirty-six (11%) adverse events resulted in hospitalization in 33 (24%) patients, of which 15 were neutropenic and 9 pyrexic. Mean duration of hospitalization was 3.4 days and 33 patients recovered uneventfully. Owners of 11 patients declined further treatment after toxicity occurred. After 25 treatments associated with toxicity, dose reductions reduced toxicity. The use of prophylactic anti-emetics, gastroprotectants and antibiotics did not reduce the frequency of gastrointestinal toxicity.
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PMID:Toxicity associated with epirubicin treatments in a large case series of dogs. 2223 53