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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Increasing insight into the mechanisms of perioperative physiologic responses and the resultant effects on patient outcome suggests that some responses may be detrimental to long-term recovery. Thus, initial belief in the adaptive "wisdom" of the body has been supplanted by the concept that a "stress-free" perioperative period may minimize detrimental physiologic responses and resultant morbidity. ⋯ Increasing evidence has emerged suggesting that such afferent nociceptive blockade may improve a variety of postoperative morbidity parameters and improve surgical outcome. We review the clinical evidence from studies examining the effects of regional anesthesia and analgesia on postoperative morbidity in specific physiologic systems.
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Neural damage is a possible consequence of general anesthesia, central nervous system blockade, and regional anesthesia. Dainage may be caused by ischaemic and mechanical or chemical factors, which may occur either alone or in combination. ⋯ Neurological complications may also result from a direct neurotoxic effect of local anesthetic agents which is concentration and dose-dependent. A better understanding of these mechanisms will provide a reliable basis for the development of improved pharmaceutical therapy.
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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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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.