Bleomycin
 Bleomycin A2 | |
| Clinical data | |
|---|---|
| Trade names | Blenoxane |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682125 |
| License data | |
| Pregnancy category |
|
subcutaneous, intrapleural[2] | |
| Drug class | Glycopeptide antibiotic |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 100% and 70% following intramuscular and subcutaneous administrations, respectively, and 45% following both intraperitoneal and intrapleural administrations[2] |
| Elimination half-life | two hours[2] |
| Excretion | Kidney (60–70%)[2] |
| Identifiers | |
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JSmol) | |
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  (what is this?) (verify) | |
Bleomycin is a medication used to treat
non-Hodgkin's lymphoma, testicular cancer, ovarian cancer, and cervical cancer among others.[6] Typically used with other cancer medications,[6] it can be given intravenously, by injection into a muscle or under the skin.[6] 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.[6][7]
Common
Chest X-rays every couple of weeks are recommended to check for this.[6] Bleomycin may cause harm to the baby if used during pregnancy.[6] It is believed to primarily work by preventing the synthesis of DNA.[6]
Bleomycin was discovered in 1962.bacterium Streptomyces verticillus.[6]
Medical uses
Cancer
Bleomycin is mostly used to treat
non-Hodgkin's disease.[6] It can be given intravenously, by intramuscular injection, or under the skin.[6]
Other uses
It may also be put inside the chest to help prevent the recurrence of a pleural effusion due to cancer.[6] 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).[11][12]
While potentially effective against bacterial infections, its toxicity prevents its use for this purpose.[6] It has been studied in the treatment of warts but is of unclear benefit.[13]
Side effects
The most common
IL-1beta in the mechanism of bleomycin-induced lung injury.[15] 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.[16] Bleomycin has also been found to disrupt the sense of taste.[17]
Lifetime cumulative dose
Bleomycin should not exceed a lifetime cumulative dose greater than 400 units.[18] Pulmonary toxicities, most commonly presenting as pulmonary fibrosis, are associated with doses of bleomycin greater than 400 units.[18]
Mechanism of action
Bleomycin acts by induction of
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.[20] In addition, these complexes also mediate lipid peroxidation and oxidation of other cellular molecules. Therefore, bleomycin is used in combination with doxorubicin in Hodgkins lymphoma, as they have additive and complementary effects on the DNA, since doxorubicin acts by intercalating between DNA strands, and also acts on topoisomerase II enzyme thus relaxing the topoisomerase complexes.[citation needed
]
Biosynthesis
Bleomycin is a
aglycon is assembled by the bleomycin megasynthetase, which is made of both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules. Nonribosomal peptides and polyketides are synthesized from amino acids and short carboxylic acids by NRPSs and PKSs, respectively. These NRPSs and PKSs use similar strategies for the assembly of these two distinct classes of natural products. Both NRPs and type I PKSs are organized into modules. The structural variations of the resulting peptide and polyketide products are determined by the number and order of modules on each NRPS and PKS protein.[citation needed
]
The biosynthesis of the bleomycin aglycon can be visualized in three stages:[citation needed]
- NRPS-mediated formation of P-3A from Ser, Asn, His, and Ala
- PKS-mediated elongation of P-3A by malonyl CoA and AdoMet to yield P-4
- NRPS-mediated elongation of P-4 by Thr to P-5 that is further elongated by β-Ala, Cys, and Cys to get P-6m.
On the basis of the bleomycin structure and the deduced functions of individual NRPS and PKS domains and modules, a linear model for the bleomycin megasynthetase-templated assembly of the bleomycin peptide/polyketide/peptide aglycon was proposed from nine amino acids and one acetate.[citation needed]
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,[21][22] primarily by the plasmid relaxation and break light assays.
History
Bleomycin was first discovered in 1962 when the Japanese scientist
Bristol-Myers Squibb
precursor, Bristol Laboratories, under the brand name Blenoxane.
Research
Bleomycin is used in research to induce pulmonary fibrosis in mice.[24]
See also
- Flagellate pigmentation from bleomycin
- Pingyangmycin (Bleomycin A5)
References
- ^ "Bleomycin Use During Pregnancy". Drugs.com. 9 August 2019. Retrieved 16 February 2020.
- ^ a b c d "Bleomycin- bleomycin sulfate injection, powder, lyophilized, for solution". DailyMed. 31 December 2019. Retrieved 16 February 2020.
- FDA. Retrieved 22 October 2023.
- ^ "Bleo-Kyowa Powder for solution for injection - Summary of Product Characteristics (SmPC)". (emc). 31 August 2018. Archived from the original on 16 February 2020. Retrieved 16 February 2020.
- ^ "Bleomycin". European Medicines Agency (EMA).
- ^ a b c d e f g h i j k l m n o p q r "Bleomycin Sulfate". The American Society of Health-System Pharmacists. Archived from the original on 8 September 2015. Retrieved 1 August 2015.
- PMID 32315458.
- ISBN 9780471899792. Archivedfrom the original on 5 March 2016.
- ISBN 9780429774546.
- hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- |intentional=yes}}.)
- PMID 29634827.
- PMID 22972052.
- ^ Thompson M. "Bleomycin and Anaesthesia" (PDF). Anaesthesia Western Australia. Archived from the original (PDF) on 8 September 2017. Retrieved 8 September 2017.
- PMID 19265174.
- PMID 12735422.
- S2CID 12671326.
- ^ a b "bleomycin [TUSOM | Pharmwiki]". tmedweb.tulane.edu. Retrieved 2 February 2022.
- ^ Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" Archived 15 May 2009 at the Wayback Machine in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach Archived 4 October 2013 at the Wayback Machine. 11 ed. 2008.
- PMID 10650103.
- PMID 28256838.
- S2CID 33531845.
- PMID 5953301.
- PMID 26289670.
In our studies, mice developed classic PF with structural alteration of the lung following intravenous bleomycin treatment
Further reading
- Claussen CA, Long EC (September 1999). "Nucleic Acid recognition by metal complexes of bleomycin". Chemical Reviews. 99 (9): 2797–2816. PMID 11749501.
- Shen B, Du L, Sanchez C, Edwards DJ, Chen M, Murrell JM (December 2001). "The biosynthetic gene cluster for the anticancer drug bleomycin from Streptomyces verticillus ATCC15003 as a model for hybrid peptide-polyketide natural product biosynthesis". Journal of Industrial Microbiology & Biotechnology. 27 (6): 378–385. S2CID 3022217.
