Cisplatin is a chemotherapy drug used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, brain tumors and neuroblastoma. This is given by injection into a blood vessel.
Common side effects include bone marrow suppression, hearing problems, kidney problems, and vomiting. Other serious side effects include numbness, walking difficulties, allergic reactions, electrolyte problems, and heart disease. Use during pregnancy is known to harm the baby. Cisplatin is present in the platinum-based platelet antineoplastic family. It works in part by binding to DNA and inhibiting its replication.
Cisplatin was discovered in 1845 and licensed for medical use in 1978/1979. It's in the List of Essential Medicines of the World Health Organization, the most effective and safe drugs needed in the health system. Wholesale costs in developing countries are about US $ 5.56 to US $ 7.98 per bottle 50 mg. In the United Kingdom, the cost of the NHS is around Ã, Â £ 17.
Video Cisplatin
Medical use
Cisplatin is given intravenously as a short-term infusion in normal saline for the treatment of dense malignancy. It is used to treat various types of cancer, including sarcoma, some carcinomas (eg, small cell lung cancer, head and neck squamous cell carcinoma and ovarian cancer), lymphoma, bladder cancer, cervical cancer, and germ cell tumors.
Cisplatin is very effective against testicular cancer; the cure rate is increased from 10% to 85%.
In addition, cisplatin is used in Auger therapy.
Often, medical practitioners and researchers should be careful about how long cisplatin remains in DMSO because it is unstable in DMSO.
Maps Cisplatin
Side effects
Cisplatin has a number of side effects that can limit its use:
- Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the patient's creatinine clearance (the size of the kidney function) is reduced. Adequate hydration and diuresis are used to prevent kidney damage. The platinum-class drug nephrotoxicity appears to be associated with reactive oxygen species and in animal models can be repaired by free radical cleaning agents (eg, amifostine). Nephrotoxicity is a dose-limiting side effect.
- Neurotoxicity (nerve damage) can be anticipated by conducting neural conduction studies before and after treatment. Common neurologic side effects of cisplatin include visual perception and hearing loss, which can occur as soon as treatment begins. While triggering apoptosis through interrupting DNA replication remains the primary mechanism of cisplatin, this has not been found to contribute to neurologic side effects. Recent studies have shown that cisplatin non-competently inhibits orthosensitive arterial sodium-hydrogen ion transporters known as NHE-1. It is mainly found in peripheral nervous system cells, which are collected in large numbers near the centers of stimuli and aural stimuli. This noncompetitive interaction has been associated with hydroelectric imbalances and cytoskeletal changes, both of which have been confirmed in vitro and in vivo. However, inhibition of NHE-1 has been found to be dependent on the dose (half inhibition = 30 Âμg/mL) and reversible.
- Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents, but it is administered with prophylactic antiemetics (ondansetron, granisetron, etc.) in combination with corticosteroids. Aprepitant combined with ondansetron and dexamethasone has been shown to be better for highly emetogenic chemotherapy than only ondansetron and dexamethasone.
- Ototoxicity (loss of hearing): there is currently no effective treatment to prevent this side effect, which may be severe. Audiometric analysis may be needed to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside class of antibiotics) can also cause muscle oxicity, and the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. Ototoxicity of both aminoglycosides and cisplatin may be related to their ability to bind melanin in the stria vascularis of the inner ear or generation of reactive oxygen species.
- Electrolyte disorders: Cisplatin may cause hypomagnesaemia, hypokalemia and hypocalcaemia. Hypocalcemia appears to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily caused by cisplatin.
- Hemolytic anemia may be developed after several cisplatin programs. It is recommended that the antibodies react with the red cisplatin-cell membrane responsible for hemolysis.
Action mechanism
Cisplatin interferes with DNA replication, which kills the fastest proliferating cells, which in theory are carcinogenic. After administration, one of the two chloride atoms is slowly moving by water to give the aquo cis - [PtCl (NH 3 ) sub sub 2 (H 2 O)] , in a process called aquation. Chloride dissociation is preferred in the cell because the intracellular chloride concentration is only 3-20% of about 100 mM of chloride concentration in the extracellular fluid.
The water molecule at cis - [PtCl (NH 3 ) 2 (H 2 O)] itself is easily removed by the N -heterocyclic base on DNA. Guanin is specially binding. After the formation of [PtCl (guanine-DNA) , crosslinking may occur by transfer of other chlorides, usually by other guanine. Cisplatin associates DNA in several different ways, disrupting cell division by mitosis. Damaged DNA leads to DNA repair mechanisms, which in turn activate apoptosis when repairs prove impossible. In 2008, researchers were able to demonstrate that apoptosis caused by cisplatin in human colon cancer cells depends on the serine protease of Omi/Htra2 mitochondria. Since this is only shown for colon carcinoma cells, it remains an open question if the Omi/Htra2 protein participates in cisplatin-induced apoptosis in carcinoma from other tissues.
The most prominent among the changes in DNA is a 1,2-intrastrand cross link with a purine base. These include the 1.2-intrastrand adduct (GpG) which makes up almost 90% of adducts and less common 1,2-intrastrand d (ApG) adduct. 1,3-intrastrand d (GpXpG) stirring occurs but is easily cut by the repair of nucleotide excision (NER). Other additions include cross-strand and nonfunctional adducts that have been postulated to contribute to cisplatin activity. Interactions with cellular proteins, especially the HMG domain protein, have also advanced as a mitotic interfering mechanism, although this may not be the primary method of action.
Although cisplatin is often designated as an alkylating agent, it has no alkyl group and is therefore unable to perform an alkylation reaction. This is properly classified as alkylating-like.
Cisplatin resistance
Cisplatin combination chemotherapy is the cornerstone of many cancer treatments. Platinum's initial response is high but the majority of cancer patients will eventually recur with cisplatin-resistant disease. Many of the mechanisms of cisplatin resistance have been proposed including changes in cellular uptake and drug depletion, increased drug detoxification, inhibition of apoptosis and improvement in DNA repair. Oxaliplatin is active in cancer cells that are highly resistant to cisplatin in the laboratory; However, there is little evidence for its activity in the clinical treatment of patients with cisplatin-resistant cancers. Paclitaxel drugs may be useful in the treatment of cancers that are resistant to cisplatin; the mechanism for this activity is unknown.
Transplatin
Transplatin, trans-steroisomer trans of cisplatin, has the formula trans - [PtCl 2 (NH 3 ) 2 ] and does not show any useful pharmacological effects. Two mechanisms have been suggested to explain the reduced anticancer effect of transplatin. First, the trans setting of the chloro ligand is thought to provide transplatin with greater chemical reactivity, causing the transplatin to be disabled before it reaches the DNA where cisplatin is given its pharmacological action. Second, the transplatin stereo-conformation is such that it can not form 1,2-intrastand adducts (GpG) formed by cisplatin in abundance.
History
The compound cis - [Pt (NH 3 ) 2 (Cl) 2 ] was first described by Michele Peyrone on in 1845, and was known for a long time as Peyrone salt. This structure was summed up by Alfred Werner in 1893. In 1965, Barnett Rosenberg, Van Camp et al. from Michigan State University found that platinum electrolysis produces a solute platinum complex that inhibits binary division in the Escherichia coli bacteria ( E. coli ). Although bacterial cell growth continues, cell division is captured, bacteria grow as filaments up to 300 times their normal length. Pt (IV) octahedral complex cis - [PtCl 4 (NH 3 ) 2 ], but not trans isomers, found to be effective in forcing the growth of filaments of E. coli cells. The planar square Pt (II) complex, cis - [PtCl 2 (NH 3 ) 2 ] turns out to be more effective in forcing the growth of filaments. These findings lead to the observation that cis - [PtCl 2 (NH 3 ) 2 ] is indeed very effective at setbacks mass sarcoma in mice. Confirmation of this invention, and the extension of the test to another tumor cell line launched the application of cisplatin drugs. Cisplatin was approved for use in testicular and ovarian cancers by the US Food and Drug Administration on 19 December 1978, and in England (and in several other European countries) in 1979.
Synthesis
The synthesis of cisplatin begins with potassium tetrachloroplatinate. Tetraiodide is formed by reaction with excess potassium iodide. The reaction with ammonia forms K 2 [PtI 2 (NH 3 ) 2 ] which is isolated as a yellow compound. When silver nitrate in water is added the insoluble silver deposit of iodide and K 2 [Pt (OH 2 ) 2 (NH 3 ) 2 ] stays in the solution. The addition of potassium chloride will form a precipitated end product. In a triiodo mediator the addition of a second ammonia ligand is governed by a trans effect.
For transplatin synthesis K 2 [PtCl 4 ] first converted to Cl 2 [Pt (NH 3 ) 4 ] by reaction with ammonia. The trans product is then formed by reaction with hydrochloric acid.
See also
- Carboplatin
- Dicycloplatin
References
Further reading
Riddell, Imogen A.; Lippard, Stephen J. (2018). "Cisplatin and Oxaliplatin: Our Current Understanding of Their Actions". In Sigel, Astrid; Sigel, Helmut; Freisinger, Eva; Sigel, Roland K. O. Metallo-Medication: Development and Action of Anticancer Agents . Berlin: de Gruyter GmbH. pp. 1-42. doi: 10.1515/9783110470734-007. ISBN: 978-3-11-046984-4.
External links
- Cisplatin: The Discovery of Anticancer Drugs by Andri Smith
- Anti-cancer agents: Treatment of Cisplatin and its analogues by Sia M. Liu (excellent detailed review)
- MedlinePlus page on cisplatin
- IARC Monograph: "Cisplatin"
Source of the article : Wikipedia
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