Expert review of neurotherapeutics
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Expert Rev Neurother · Jan 2009
ReviewLacosamide: pharmacology, mechanisms of action and pooled efficacy and safety data in partial-onset seizures.
Lacosamide is an antiepileptic drug approved in the USA and Europe as adjunctive therapy for partial-onset seizures. Studies suggest that lacosamide selectively enhances slow inactivation of voltage-gated sodium channels and possibly interacts with collapsin response mediator protein-2. ⋯ Clinical trials show that lacosamide is well tolerated; the most common adverse events were dizziness, nausea and vomiting. In a Phase II/III pooled analysis, lacosamide 200 and 400 mg/day significantly reduced partial-onset seizure frequency and improved the 50% responder rate compared with placebo.
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Generalized convulsive status epilepticus is a neurologic and medical emergency, with significant morbidity and mortality. First-line treatment includes administration of intravenous benzodiazepines. ⋯ Refractory status epilepticus necessitates the use of anesthetic agents such as pentobarbital, midazolam or propofol, with monitoring of treatment effect by continuous EEG. Nonconvulsive status epilepticus should be treated expeditiously but is not as threatening to health as convulsive status epilepticus.
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Expert Rev Neurother · Nov 2008
ReviewCurrent challenges and future prospects in management of neuropathic pain.
Management of neuropathic pain is a challenge, as the currently available drugs usually do not target the multiple underlying mechanisms. This article will briefly review the currently available therapies for neuropathic pain as an introduction to those in clinical trials. The two most common conditions in clinical trials of neuropathic pain are diabetic neuropathy and postherpetic neuralgia. ⋯ Some of the novel targets for developing therapies for neuropathic pain include chemokine receptors, glial cells and cytokines. The review includes various suggestions for management of neuropathic pain, including multidisciplinary and personalized approaches. Considerable improvements are anticipated in the management of neuropathic pain in the next 5 years, although it is difficult to predict the chances of success of any particular product in development, considering the high rate of failures of previous trials.
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Expert Rev Neurother · Nov 2008
ReviewA new tr(i)p to sense pain: TRPA1 channel as a target for novel analgesics.
Pain sensation occurs at multiple levels of the nervous system, involving a myriad of molecules and signaling pathways that contribute to the detection of noxious stimuli, and the modulation, initiation and propagation of electrical activity in nociceptors, a subset of primary sensory neurons. The fact that several types of ion channels or their splice variants are highly expressed in nociceptors and are critical for pain transduction has prompted scientists to examine their physiological roles in order to better understand the neuromolecular mechanisms of the pain pathway. Recent reports have demonstrated that TRPA1, a member of the mammalian transient receptor potential cation channel family, acts as a key chemical nocisensor in response to diverse chemical stimuli. The TRPA1 channel represents a new target for novel analgesics to specifically eliminate pain sensation of various stimuli.
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Expert Rev Neurother · Nov 2008
Review Meta AnalysisExtended-release epidural morphine (DepoDur): review and safety analysis.
Extended-release epidural morphine (EREM) provides effective postoperative analgesia for 48 h following injection. It is administered as a single bolus into the lumbar epidural space, and is indicated for lower abdominal and lower extremity surgery associated with moderate-to-severe pain. While its efficacy has been well documented in randomized controlled trials, the safety and clinically appropriate dosing are less well defined. ⋯ Vomiting was also increased with EREM 15 mg or greater compared with placebo (odds ratio: 0.40; 95% CI: 0.18-0.89; p = 0.02; NNT = 5). A multimodal analgesic regime is recommended to permit the use of lower EREM doses, thus reducing the risk for adverse effects including respiratory depression. Prophylactic time-contingent antiemetics are also recommended when EREM is used.