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Some Antiviral and Antineoplastic Drugs and Other Pharmaceutical Agents - Iarc Monograph on the Carcinogenic Risks to Humans (Paperback)
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Some Antiviral and Antineoplastic Drugs and Other Pharmaceutical Agents - Iarc Monograph on the Carcinogenic Risks to Humans (Paperback)
Series: IARC Monographs, No. 76
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Evaluates the carcinogenic risks to humans posed by the use of four
antiretroviral agents, four DNA topoisomerase II inhibitors used in
the treatment of cancer, and an additional three pharmaceutical
agents (hydroxyures, phenolphthalein, and vitamin K substances).
The volume marks the first IARC evaluation of nucleoside analogs
that act as antiviral agents. The evaluation responds in part to
recent findings that zidovudine (AZT), an effective antiretroviral
agent now being given to pregnant HIV-infected women to prevent
maternal-to-fetal transmission of the virus, is a transplacental
carcinogen in mice. The opening monograph evaluates the
carcinogenicity to humans of the antiretroviral nucleoside analogs
zidovudine (AZT), zalcitabine (ddC), and didanosine (ddI), and the
antiherpesvirus drug aciclovir. Of these, aciclovir and didanosine
could not be classified on the basis of available data. For
zidovudine, transplacental administration to mice resulted in an
increased incidence and multiplicity of lung and liver tumours and
in an increased incidence of female reproductive tract tumours in
one study, but not in another involving treatment at a lower
dose.Despite observation of toxic effects in some studies of
humans, human carcinogenicity data were judged to provide
inadequate evidence of carcinogenicity in humans. Zidovudine was
classified as possibly carcinogenic to humans. Similar weaknesses
in human carcinogenicity data for zalcitabine, which consistently
induces thymic lymphomas in mice, resulted in its classification as
possibly carcinogenic to humans. The second monograph evaluates
four DNA topoisomerase II inhibitors: etoposide, teniposide,
mitoxantrone, and amsacrine. Of these, etoposide - one of the most
widely used and effective cytotoxic drugs in combination therapy -
was classified as probably carcinogenic to humans, and etoposide in
combination with cisplatin and bleomycin was judged to be
carcinogenic to humans. Teniposide was classified as probably
carcinogenic to humans, and mitoxantrone and amsacrine were
classified as possibly carcinogenic to humans. Of the three
pharmaceutical agents evaluated in the final monograph,
hydroxyurea, which is widely used in cancer treatment and,
increasingly, in combination with didanosine in HIV infection,
could not be classified.Phenolphthalein, a widely used laxative now
being withdrawn from the market in many countries because of
toxicological concerns, was classified as possibly carcinogenic.
Vitamin K substances could not be classified on the basis of
available evidence.
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