Sodium channel blockers toxicity

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... 

Elecainide, proprietary name Tambocor, is a sodium channel blocker with cardiac activity like disopyramide. The drug has significant toxicity in patients with myocardial infarction and has therefore fallen out of favor. For those patients who fail to respond to other sodium channel blockers, it might be a drug of last resort. 

Marine toxins may be developed from marine organisms. Examples include saxitoxin, tetrodotoxin, palytoxin, brevetoxins, and microcystin. Saxitoxin is a sodium-channel blocker and is most toxic by inhalation compared to the other routes of exposure. Saxitoxin and tetrodotoxin are similar in mechanical action, toxicity, and physical attributes. They can be lethal within a few minutes when inhaled. It has not yet been chemically synthesized efficiently, or easily created in large quantities from natural sources. Palytoxin is produced from soft coral and is highly toxic. It is, however, difficult to produce or harvest from nature. 

Huot, R.I., Armstrong, D.L., and Chanh, T.C. 1989. Protection against nerve toxicity by monoclonal antibodies to the sodium channel blocker tetrodotoxin. J. Clirc Invest. 83, 1821-1826. 

In overdose, 3 blockers block both and 32 adrenoceptors selectivity, if any, is lost at high dosage. The most toxic blocker is propranolol. As little as two to three times the therapeutic dose can cause serious toxicity. This may be because propranolol has additional properties At high doses it may cause sodium channel blocking effects similar to those seen with quinidine-like drugs, and it is lipophilic, allowing it to enter the CNS (see Chapter 10). 

An impressive list of compounds has been used to decrease cisplatin nephrotoxicity [ANF, glycine, diethyldithiocarbamate, calcium channel blockers, cimetidine, sodium thiosulphate, glutathione, other sulfidryl compounds,. ..]. Among them only sodium thiosulphate has received a significant clinical application and has been reported to reduce the renal toxicity of cisplatin administered locally by either the intra-arterial, intra-peritoneal or intrathoracic routes [50, 51]. However, controversies still exists as to the effect of sodium thiosulphate on cisplatin antitumor activity. Thus sodium thiosulphate may be most useful in combination with intraperitoneal cisplatin where it confers renal protection without altering local effects of cisplatin [51]. 

A series of potent alkaloids were first isolated from den-drobatid frogs of western Colombia and northwestern Ecuador, but are now known to be more widespread in distribution. These alkaloids affect at least three classes of channels in nerve and muscle. The first two are receptor-regulated channels, in particular the nicotinic acetylcholine receptor channel. The histrionicotoxins are noncompetitive blockers of this receptor-channel complex (Daly et al, 1993). The second class of channels are the voltage-dependent sodium channels. Histrionicotoxins reduce conductances in a manner reminiscent of local anesthetics (Daly et al., 1993). Despite these effects, these alkaloids have relatively low toxicity (Daly et al., 1993). 

Amiodarone (Cordarone) is an iodine-containing benzo-furan derivative identified as a class III agent because it predominantly prolongs action potentials. Amiodarone also blocks sodium and calcium channels and is a noncompetitive p-receptor blocker. Amiodarone is effective for the treatment of most arrhythmias. Toxicity associated with amiodarone has led the U. S. Food and Drug Administration (FDA) to recommend that it be reserved for use in patients with life-threatening arrhythmias. 

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