Pharmacology
Summary
Platins, also known as platinum-based chemotherapeutic agents, are cytotoxic drugs that target DNA by forming intrastrand and interstrand cross-links, inhibiting DNA synthesis and function through the incorporation of platinum.
The cytotoxic effects of platinum, the key component, were first discovered when it was observed to inhibit the growth of E. Coli. Platinum analogs such as cisplatin, carboplatin, and oxaliplatin have since been developed. Similar to alkylating agents, platins target DNA by forming intrastrand and interstrand cross-links, inhibiting DNA synthesis and function. But instead of crosslinking DNA with alkyl groups, these agents crosslink with platinum.
Platins have demonstrated efficacy against solid cancers including non-small cell and small cell lung cancers, as well as testicular, ovarian, and bladder cancers. Adverse side effects include neurotoxicity, like ototoxicity and peripheral neuropathy, along with nephrotoxicity. Cisplatin carries the highest risk for side effects, which includes numbness, paresthesias, pain in a stocking-glove distribution, or potential renal dysfunction. Amifostine can be used to reduce cisplatin-induced nephrotoxicity by binding to and deactivating cisplatin's reactive metabolites. Careful administration of IV fluids can also markedly reduce the risk of nephrotoxicity. Lastly, carboplatin differs from the other drugs in that its main toxicity is myelosuppression.
Lesson Outline
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FAQs
The main cytotoxic platinum analogs include cisplatin, carboplatin, and oxaliplatin. They are used to treat a wide variety of solid malignancies, including non-small cell lung cancer, small cell lung cancer, testicular cancer, ovarian cancer, and bladder cancer.
Platinum analogs can cause a range of side effects. The side effects of cisplatin, for example, includes ototoxicity (which can lead to sensorineural hearing loss and tinnitus), neurotoxicity (which can result in peripheral neuropathy), and nephrotoxicity (which can cause acute kidney injury). Other side effects include myelosuppression and immunosuppression (leading to an increased risk of infection) as in the case of carboplatin.
Platinum analogs function by binding to DNA and forming intrastrand and interstrand crosslinks through the insertion of platinum. This disrupts DNA synthesis, thereby inhibiting cell division and leading to cell death in rapidly dividing cells, such as cancer cells.
Cisplatin-induced nephrotoxicity can be prevented using several methods including the use of amifostine, an organic thiophosphate (which scavenges free radicals produced by cisplatin in the kidney) and IV saline diuresis.
