Sodium blockers

The existence of nitric oxide synthase (NOS) in phagocytes (see below) provides a different kind of stimulation and the inhibition of NADPH oxidase. It has been found [72] that the low physiological concentrations of peroxynitrite formed from NO and superoxide stimulated superoxide production by PMA-activated human PMNs through the ERK MAPK pathway, while higher peroxynitrite concentrations inhibited it. Moreover, NADPH oxidase was inhibited by lidocaine, a sodium-blocker, in OZ-activated neutrophils through the suppression of p47phox translocation [73]. 

These principles are important in understanding additive drug combinations (e.g., quinidine and mexiletine), antagonistic combinations (e.g., flecainide and lidocaine), and potential antidotes to excess sodium channel blockade (e.g., sodium bicarbonate or propranolol). They also explain a number of clinical observations, such as why lidocaine-like drugs are relatively ineffective for supraventricular tachycardia. The type Ib drugs are fast on/off, inactivated sodium blockers atrial cells, however, have a very brief inactivated phase relative to ventricular tissue. 

Zaccara G, GiovanneUi F, Maratea D, Fadda V, Verrotti A. Neurological adverse events of new generation sodium blocker antiepileptic drugs. Meta-analysis of randomized, double-bhnded studies with eshcarbazepine acetate, lacosamide and oxcarbazepine. Seizure September 2013 22(7) 528-36. 

Class I Antiarrhythmic Agents The Sodium Channel Blockers... 

Class IB agents (Sodium channel blockers) [73-78-9] C H23C1N20 H2O Xylocaine, Dalcaine... 

Elestolol sulfate is a nonselective, ultrashort acting P-adrenoceptor blocker. It has no ISA and produces weak inhibition of the fast sodium channel. The dmg is under clinical investigation for supraventricular tachyarrhythmias, unstable angina, and acute MI. In humans, flestolol has hemodynamics and electrophysiologic effects similar to those of other P-adrenoceptor blockers. The pharmacokinetics of flestolol are similar to those of esmolol. It is 50 times more potent than esmolol and the elimination half-life is 7.2 min. Recovery from P-adrenoceptor blockade is 30—45 min after stopping iv infusions. The dmg is hydrolyzed by tissue esterases and no active metabohtes of flestolol have been identified (41). 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

Calcium channel blockers cause more pronounced lowering of blood pressure in hypertensive patients than in normotensive individuals. Generally, all calcium channel blockers cause an immediate increase in PRA during acute treatment in patients having hypertension but PRA is normalized during chronic treatment despite the sustained decrease in blood pressure. These agents also do not generally produce sodium and water retention, unlike the conventional vasodilators. This is because they produce diuretic effects by direct actions on the kidney. 

Tanelian DL, Brose WG (1991) Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers lidocaine, carbamazepine, and mexiletine. Anesthesiology 74 949-951... 

Pharmacological intervention NSAIDs, local anesthetics, opioid analgesics, sodium-channel blockers Opioid analgesics, NSAIDs, calcium-channel blockers ... 

Hyaluronic acid is a linear polysaccharide found in the highest concentrations in soft connective tissues where it fills an important structural role in the organization of the extracellular matrix (23,24). It has been used in ophthalmic preparations to enhance ocular absorption of timolol, a beta blocker used for the treatment of glaucoma (25), and in a viscoelastic tear formulation for conjunctivitis (26). The covalent binding of adriamycin and daunomycin to sodium hy-aluronate to produce water-soluble conjugates was recently reported (27). 

Tetrodotoxin (TTX) and saxitoxin (STX) are potent sodium channel blockers that are found in phylogenetically diverse species of marine life. The wide distribution of TTX and STX has resulted in speculation that bacteria are the source of these toxins. Recently, investigators have reported isolation of marine bacteria, including Vibrio Alteromonas, Plesiomonas, and Pseudomonas species, that produce TTX and STX. This chapter details the methods and results of research to define bacterial sources of TTX and STX. 

This chapter reviews recent experimental evidence of a bacterial source of sodium channel blockers, principly TTXs. These findings support the hypothesis that procaryotic organisms produce TTXs which contaminate oceanic food chains. 

Extraction of Sodium Channel Blockers. A review of published reports shows that methods for purification of sodium channel blockers from bacterial cultures are similar to techniques for isolation of TTX and STX from pufferfish and dinoflagellates (30, 31, 38, 39). Typically, cell pellets of bacterial cultures are extracted with hot 0.1% acetic acid, the resulting supernatant ultra-filtered, lyo-philized, and reconstituted in a minimal volume of 0.1% acetic acid. Culture media can also be extracted for TTX by a similar procedure (Ji). Both cell and supernatant extracts are analyzed further by gel filtration chromatography and other biological, chemical, and immunological methods. Few reports describe purification schemes that include extraction of control samples of bacteriological media (e.g., broths and agars) which may be derived from marine plant and animal tissues. 

Tissue Culture Assay. Kogure et al. (48) report a novel tissue culture assay for detecting several types of sodium channel blockers. The mouse neuroblastoma cell line ATCC CCL 131 is grown in RPMI 1640 supplemented with 13.5% fetal bovine serum and 100 pg/ml gentamycin, in an atmosphere of 5% C0 95% air at 37 C. Ninety-six well plates are seeded with 1 x 10 cells in 200 pi of medium containing 1 mM ouabain and 0.075 mM veratridine. Veratridine and ouabain cause neuroblastoma cells to round-up and die. In the presence of sodium channel blockers (e.g., TTXs or STXs), the lethal action of veratridine is obviated and cells retain normal morphology and viability. An important feature of this assay is that a positive test for sodium channel blockers results in normal cell viability. Since bacterial extracts can contain cytotoxic components, this assay offers an advantage over tests that use cell death as an endpoint. The minimum detectable level of TTX is approximately 3 nM, or approximately 1/1000 mouse unit. 

Interestingly, they report that E. coli, a normal inhabitant of the mammalian gastrointestinal tract, produces anhydro-TTX. Unidentified sodium channel blockers have also been detected in cultures of Vibrio cholerae an estuarine bacterium and human enteropathogen (54). 

Aeromonas species producing sodium channel blockers, 80r,82 Agelas dispar, 320... 

Alteromonas species producing sodium channel blockers, 80r,82 Anabaena flos-aquae neurotoxins, 88 toxic principle, 108 Analyses, definition, 43 Anatoxin(s) isolation, 88 types, 88,91 Anatoxin a... 

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