NA channel blockers: the risks.
Posted: Wed Aug 01, 2007 6:37 am
Although NA channel blockers seem to have beneficial effects, there are a couple of cautions here: first, withdrawal seems to cause serious complications. However they don't mention how sudden the withdrawal was, so maybe it will be a case of simply not stopping them quickly, as with several other drugs. Second, the sentence, " the effect of sodium channel blockers on immune cells", makes me wonder what that effect was.
Hopefully, this just amounts to the discovery of a couple of contraindications.
http://www.ncbi.nlm.nih.gov
posted by doublehelix 4 days ago view profile a.al { color: #000000; text-decoration: none } a.al:hover { text-decoration: underline } Ann Neurol. 2007 Jul 25;62(1):21-33.
Black JA, Liu S, Carrithers M, Carrithers LM, Waxman SG
Discuss | category: Neurology
OBJECTIVE: In vitro observations and studies in murine experimental autoimmune encephalomyelitis (EAE) have shown protective on central nervous system axons and improved clinical status when treatment is continued throughout the period of observation. Several clinical studies of sodium channel blockers are under way in patients with multiple sclerosis. Here we asked whether a protective effect would persist after withdrawal of a sodium channel blocker. METHODS: We studied a mouse model of myelin oligodendrocyte glycoprotein-induced EAE treated with phenytoin or carbamazepine. RESULTS: Both phenytoin and carbamazepine significantly improved the clinical course of the disease. Withdrawal of phenytoin resulted in acute exacerbation, accompanied by a significantly increased inflammatory infiltrate within the central nervous system and the death of nearly 60% of EAE mice. There were no clinical worsening or deaths in control mice after withdrawal of phenytoin. Withdrawal of carbamazepine led to acute worsening of EAE symptoms, increased inflammatory infiltrate, and was associated with the death of 8% of mice. INTERPRETATION: These results, together with results showing effects of sodium channel blockers in immune cells, raise questions about the long-term effects of sodium channel blockers in neuroinflammatory disorders, and suggest that clinical studies of sodium channel blockers in these disorders should be planned carefully. Ann Neurol 2007.
Hopefully, this just amounts to the discovery of a couple of contraindications.
http://www.ncbi.nlm.nih.gov
posted by doublehelix 4 days ago view profile a.al { color: #000000; text-decoration: none } a.al:hover { text-decoration: underline } Ann Neurol. 2007 Jul 25;62(1):21-33.
Black JA, Liu S, Carrithers M, Carrithers LM, Waxman SG
Discuss | category: Neurology
OBJECTIVE: In vitro observations and studies in murine experimental autoimmune encephalomyelitis (EAE) have shown protective on central nervous system axons and improved clinical status when treatment is continued throughout the period of observation. Several clinical studies of sodium channel blockers are under way in patients with multiple sclerosis. Here we asked whether a protective effect would persist after withdrawal of a sodium channel blocker. METHODS: We studied a mouse model of myelin oligodendrocyte glycoprotein-induced EAE treated with phenytoin or carbamazepine. RESULTS: Both phenytoin and carbamazepine significantly improved the clinical course of the disease. Withdrawal of phenytoin resulted in acute exacerbation, accompanied by a significantly increased inflammatory infiltrate within the central nervous system and the death of nearly 60% of EAE mice. There were no clinical worsening or deaths in control mice after withdrawal of phenytoin. Withdrawal of carbamazepine led to acute worsening of EAE symptoms, increased inflammatory infiltrate, and was associated with the death of 8% of mice. INTERPRETATION: These results, together with results showing effects of sodium channel blockers in immune cells, raise questions about the long-term effects of sodium channel blockers in neuroinflammatory disorders, and suggest that clinical studies of sodium channel blockers in these disorders should be planned carefully. Ann Neurol 2007.