Bleomycin

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Bleomycin is a medication primarily used to treat cancer.<ref name=AHFS2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> This includes Hodgkin's lymphoma, non-Hodgkin's lymphoma, testicular cancer, ovarian cancer, and cervical cancer among others.<ref name=AHFS2015/> Typically used with other cancer medications,<ref name=AHFS2015/> it can be given intravenously, by injection into a muscle or under the skin.<ref name=AHFS2015/> It may also be administered inside the chest to help prevent the recurrence of a pleural effusion due to cancer; however talc is better for this.<ref name=AHFS2015/><ref>Template:Cite journal</ref> It may sometimes be used to treat other difficult-to-treat skin lesions such as plantar warts in immunocompromised patients.

Common side effects include fever, weight loss, vomiting, and rash.<ref name=AHFS2015/> A severe type of anaphylaxis may occur.<ref name=AHFS2015/> It may also cause inflammation of the lungs that can result in lung scarring.<ref name=AHFS2015/> Chest X-rays every couple of weeks are recommended to check for this.<ref name=AHFS2015/> Bleomycin may cause harm to the baby if used during pregnancy.<ref name=AHFS2015/> It is believed to primarily work by preventing the synthesis of DNA.<ref name=AHFS2015/>

Bleomycin was discovered in 1962.<ref>Template:Cite book</ref><ref>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref> It is available as a generic medication.<ref name=AHFS2015/> It is made by the bacterium Streptomyces verticillus.<ref name=AHFS2015/>

Medical usesEdit

CancerEdit

Bleomycin is mostly used to treat cancer.<ref name=AHFS2015/> This includes testicular cancer, ovarian cancer, and Hodgkin's disease, and less commonly non-Hodgkin's disease.<ref name=AHFS2015/> It can be given intravenously, by intramuscular injection, or under the skin.<ref name=AHFS2015/>

Other usesEdit

It may also be put inside the chest to help prevent the recurrence of a pleural effusion due to cancer.<ref name=AHFS2015/> However, for scarring down the pleura, talc appears to be the better option although indwelling pleural catheters are at least as effective in reducing the symptoms of an effusion(such as dyspnea).<ref name="Ag2004">Template:Cite journal Template:Retracted</ref><ref>Template:Cite journal</ref>

While potentially effective against bacterial infections, its toxicity prevents its use for this purpose.<ref name=AHFS2015/> It has been studied in the treatment of warts but is of unclear benefit.<ref>Template:Cite journal</ref>

Side effectsEdit

The most common side effects are flu-like symptoms and include fever, rash, dermatographism, hyperpigmentation, alopecia (hair loss), chills, and Raynaud's phenomenon (discoloration of fingers and toes). The most serious complication of bleomycin, occurring upon increasing dosage, is pulmonary fibrosis and impaired lung function. It has been suggested that bleomycin induces sensitivity to oxygen toxicity<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and recent studies support the role of the proinflammatory cytokines IL-18 and IL-1beta in the mechanism of bleomycin-induced lung injury.<ref name="pmid19265174">Template:Cite journal</ref> Any previous treatment with bleomycin should therefore always be disclosed to the anaesthetist prior to undergoing a procedure requiring general anaesthesia. Due to the oxygen sensitive nature of bleomycin, and the theorised increased likelihood of developing pulmonary fibrosis following supplemental oxygen therapy, it has been questioned whether patients should take part in scuba diving following treatment with the drug.<ref>Template:Cite journal</ref> Bleomycin has also been found to disrupt the sense of taste.<ref>Template:Cite journal</ref>

Lifetime cumulative doseEdit

Bleomycin should not exceed a lifetime cumulative dose greater than 400 units.<ref name=":0">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Pulmonary toxicities, most commonly presenting as pulmonary fibrosis, are associated with doses of bleomycin greater than 400 units.<ref name=":0" />

Mechanism of actionEdit

Bleomycin acts by induction of DNA strand breaks.<ref>Template:Cite book</ref> Some studies suggest bleomycin also inhibits incorporation of thymidine into DNA strands. DNA cleavage by bleomycin depends on oxygen and metal ions, at least in vitro. The exact mechanism of DNA strand scission is unresolved, but it has been suggested that bleomycin chelates metal ions (primarily iron), producing a pseudoenzyme that reacts with oxygen to produce superoxide and hydroxide free radicals that cleave DNA. An alternative hypothesis states that bleomycin may bind at specific sites in the DNA strand and induce scission by abstracting the hydrogen atom from the base, resulting in strand cleavage as the base undergoes a Criegee-type rearrangement, or forms an alkali-labile lesion.<ref>Template:Cite journal</ref>

BiosynthesisEdit

Biosynthesis of bleomycin is completed by glycosylation of the aglycones. Bleomycin naturally occurring-analogues have two to three sugar molecules, and DNA cleavage activities of these analogues have been assessed,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> primarily by the plasmid relaxation and break light assays.

HistoryEdit

Template:See also Bleomycin was first discovered in 1962 when the Japanese scientist Hamao Umezawa found anticancer activity while screening culture filtrates of Streptomyces verticillus. Umezawa published his discovery in 1966.<ref name="pmid5953301">Template:Cite journal</ref> The drug was launched in Japan by Nippon Kayaku in 1969. In the US, bleomycin gained FDA approval in July 1973. It was initially marketed in the US by the Bristol-Myers Squibb precursor, Bristol Laboratories, under the brand name Blenoxane.

ResearchEdit

Bleomycin is used in research to induce pulmonary fibrosis in mice.<ref>Template:Cite journal</ref> It accomplishes this by preventing alveolar cell proliferation, which in turn leads to cellular senescence.

ReferencesEdit

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