Current topics in medicinal chemistry
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Non-selective NSAIDs enhance the risk of serious ulcer complications (bleeding, perforation, obstruction), hospitalization and death about 3-10-fold. The gastrointestinal side effects of NSAIDs have a considerable economical burden, since they are responsible for 5-10 billion dollars in hospitalization charges and lost work time. NSAIDs cause gastrointestinal damage by both topical and systemic effects. ⋯ Current data suggest, that Coxibs are associated with a significantly lower risk of serious lower GI events than traditional NSAIDs. It is now under debate, who should receive COX-2-selective inhibitors instead of classical NSAIDs, since Coxibs are much more expensive. Data from cost-effectiveness studies suggest, that Coxibs should currently be used only in patients with high risks of GI complications.
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Review Comparative Study
Clinical application of ropivacaine in obstetrics.
Ropivacaine is a new long-acting local anesthetic which is a pure (S)-(-)-enantiomer, with an efficacy profile similar to that of bupivacaine. Compared in equal doses, ropivacaine shows more separation between sensory and motor blockade than bupivacaine. Moreover, ropivacaine has a lower systemic toxicity than bupivacaine. ⋯ For Cesarean section, both drugs provide similar analgesia when given in equal doses, but motor block is less pronounced with ropivacaine. Neonatal outcome as determined by Apgar scores and Neurological Adaptive Capacity Scores (NACS) is also similar. For epidural pain relief during labor and delivery, both drugs are equally effective, either when given alone or in combination with opioids; a meta-analysis of six studies showed that compared to bupivacaine, the use of ropivacaine is associated with significantly less motor block and instrumental deliveries.
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Review Historical Article
From cocaine to ropivacaine: the history of local anesthetic drugs.
In 1850, about three centuries after the conquest of Peru by Pizzaro, the Austrian von Scherzer brought a sufficient quantum of coca leaves to Europe to permit the isolation of cocaine. As suggested by his friend Sigmund Freud, descriptions of the properties of the coca prompted the Austrian Koller to perform in 1884 the first clinical operation under local anesthesia, by administration of cocaine on the eye. The use of cocaine for local and regional anesthesia rapidly spread throughout Europe and America. ⋯ Numerous experimental studies were conducted to identify the fine cellular mechanism of this toxicity, which refines our understanding of the action of local anesthetics. The identification of optically active isomers of the mepivacaine family led to the selection of ropivacaine, a pure S-(-) enantiomer, whose toxicology was selectively and extensively studied before its introduction on the market in 1996. During the rapid and extensive use of ropivacaine in the clinic, unwanted side-effects have been found to be very limited.
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Ropivacaine is a new amide local anaesthetic, which is the first commercially available in its category as a pure S-(-) enantiomer. In most recent studies, ropivacaine exhibited a very close pharmacodynamic profile to equipotent doses of bupivacaine. Concentrations of 0.5%, 0.75% and 1% (5, 7.5 and 10 mg/mL, respectively) ropivacaine are used for intraoperative anaesthesia, while the concentration of 0.2% (2 mg/mL) is preferred for postoperative analgesia, either alone or in combination with opioids and/or clonidine. ⋯ The primary benefit of ropivacaine is its lower toxicity, mainly lower cardiotoxicity, following accidental intravascular injection. This higher therapeutic index leads to an improved safety profile as compared with potent local anaesthetics such as racemic bupivacaine. For that reason, ropivacaine is a good choice for both intraoperative and postoperative regional anaesthesia and analgesia.
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Ropivacaine, the S-(-)-enantiomer of N-(2,6-dimethylphenyl)-1-propyl-2-piperidinecarboxamide is a new long-acting local anesthetic. This review demonstrates that it is effective in brachial plexus anesthesia. It is at least as efficient as bupivacaine in terms of quality, duration of analgesia, anesthesia, and motor block. ⋯ Further investigations are required to assess its efficacy during such block. Because of lower CNS and cardiac toxicity, ropivacaine is safer than bupivacaine. It would be thus the preferred local anesthetic for brachial plexus blockade when long-lasting anesthesia and analgesia is required.