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Trade names | Blenoxane |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682125 |
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Routes of administration | intravenous, intramuscular, subcutaneous, intrapleural [2] |
Drug class | Glycopeptide antibiotic |
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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] |
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Chemical and physical data | |
Formula | C55H84N17O21S3 |
Molar mass | 1415.56 g·mol−1 |
3D model (JSmol) | |
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Bleomycin is a medication primarily used to treat cancer. [6] This includes Hodgkin's lymphoma, 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] It may sometimes be used to treat other difficult-to-treat skin lesions such as plantars warts in immunocompromised patients.
Common side effects include fever, weight loss, vomiting, and rash. [6] A severe type of anaphylaxis may occur. [6] It may also cause inflammation of the lungs that can result in lung scarring. [6] 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. [8] [9] It is on the World Health Organization's List of Essential Medicines. [10] It is available as a generic medication. [6] It is made by the bacterium Streptomyces verticillus . [6]
Bleomycin is mostly used to treat cancer. [6] This includes testicular cancer, ovarian cancer, and Hodgkin's disease, and less commonly non-Hodgkin's disease. [6] It can be given intravenously, by intramuscular injection, or under the skin. [6]
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]
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 [14] and recent studies support the role of the proinflammatory cytokines IL-18 and 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]
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]
Bleomycin acts by induction of DNA strand breaks. [19] 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. [20]
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.
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. [23] 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.
Bleomycin is used in research to induce pulmonary fibrosis in mice. [24] It accomplishes this by preventing alveolar cell proliferation, which in turn leads to cellular senescence.
Chemotherapy is the type of cancer treatment that uses one or more anti-cancer drugs in a standard regimen. Chemotherapy may be given with a curative intent, or it may aim only to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity of the condition is variable.
Pleurisy, also known as pleuritis, is inflammation of the membranes that surround the lungs and line the chest cavity (pleurae). This can result in a sharp chest pain while breathing. Occasionally the pain may be a constant dull ache. Other symptoms may include shortness of breath, cough, fever, or weight loss, depending on the underlying cause.
A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilogram weight per hour, and is cleared by lymphatic absorption leaving behind only 5–15 millilitres of fluid, which helps to maintain a functional vacuum between the parietal and visceral pleurae. Excess fluid within the pleural space can impair inspiration by upsetting the functional vacuum and hydrostatically increasing the resistance against lung expansion, resulting in a fully or partially collapsed lung.
Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors.
Transient tachypnea of the newborn is a respiratory problem that can be seen in the newborn shortly after delivery. It is caused by retained fetal lung fluid due to impaired clearance mechanisms. It is the most common cause of respiratory distress in term neonates. It consists of a period of tachypnea. Usually, this condition resolves over 24–72 hours. Treatment is supportive and may include supplemental oxygen and antibiotics. The chest x-ray shows hyperinflation of the lungs including prominent pulmonary vascular markings, flattening of the diaphragm, and fluid in the horizontal fissure of the right lung.
Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory diseases affecting the interstitium and space around the alveoli of the lungs. It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, and perivascular and perilymphatic tissues. It may occur when an injury to the lungs triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair damage, but in interstitial lung disease, the repair process is disrupted, and the tissue around the air sacs (alveoli) becomes scarred and thickened. This makes it more difficult for oxygen to pass into the bloodstream. The disease presents itself with the following symptoms: shortness of breath, nonproductive coughing, fatigue, and weight loss, which tend to develop slowly, over several months. The average rate of survival for someone with this disease is between three and five years. The term ILD is used to distinguish these diseases from obstructive airways diseases.
Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer. It is given by injection into a vein.
Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.
ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, replacing the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:
Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively and postoperatively.
Dasatinib, sold under the brand name Sprycel among others, is a targeted therapy medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Specifically it is used to treat cases that are Philadelphia chromosome-positive (Ph+). It is taken by mouth.
Malignant pleural effusion is a condition in which cancer causes an abnormal amount of fluid to collect between the thin layers of tissue (pleura) lining the outside of the lung and the wall of the chest cavity. Lung cancer and breast cancer account for about 50-65% of malignant pleural effusions. Other common causes include pleural mesothelioma and lymphoma.
Polypeptide antibiotics are a chemically diverse class of anti-infective and antitumor antibiotics containing non-protein polypeptide chains. Examples of this class include actinomycin, bacitracin, colistin, and polymyxin B. Actinomycin-D has found use in cancer chemotherapy. Most other polypeptide antibiotics are too toxic for systemic administration, but can safely be administered topically to the skin as an antiseptic for shallow cuts and abrasions.
Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.
Pirfenidone, sold under the brand name Pirespa among others, is a medication used for the treatment of idiopathic pulmonary fibrosis. It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II.
Pingyangmycin (also known as bleomycin A5) is an antitumor glycopeptide antibiotic belonging to the bleomycin family, which is produced by Streptomyces verticillus var. pingyangensis n.sp., a variety of Streptomyces verticillus. It was discovered in 1969 at Pingyang County of Zhejiang Province in China, and was brought into clinical use in 1978.
Asbestos-related diseases are disorders of the lung and pleura caused by the inhalation of asbestos fibres. Asbestos-related diseases include non-malignant disorders such as asbestosis, diffuse pleural thickening, pleural plaques, pleural effusion, rounded atelectasis and malignancies such as lung cancer and malignant mesothelioma.
Streptomyces verticillus is a species of Gram-positive bacteria in the genus Streptomyces. Whilst screening fermentation broths of this species for bioactivity in the early 1960s, Hamao Umezawa and colleagues at the Institute of Microbial Chemistry in Tokyo identified a family of glycopeptide antitumor antibiotics called the bleomycins. Examples of the bleomycins in clinical use include bleomycin A2 (also known as bleomycin) and bleomycin A5 (also known as pingyangmycin). Both are used to treat lymphomas (e.g. Hodgkin's lymphoma), head and neck cancer, and testicular cancer.
Lung surgery is a type of thoracic surgery involving the repair or removal of lung tissue, and can be used to treat a variety of conditions ranging from lung cancer to pulmonary hypertension. Common operations include anatomic and nonanatomic resections, pleurodesis and lung transplants. Though records of lung surgery date back to the Classical Age, new techniques such as VATS continue to be developed.
In our studies, mice developed classic PF with structural alteration of the lung following intravenous bleomycin treatment