I- Lidocaine

CYP3A4 i Lidocaine metabolism to MEGX Plasma concentrations of MEGX severe cirrhosis = 4.6 ng/mL moderate cirrhosis = 19.1 ng/mL mild cirrhosis = 32.8 ng/mL control = 53.4 ng/mL Hence the more severe the cirrhosis the lower the metabolism of lidocaine to MEGX due to 4- CYP3A4 [44]... 

I b With shortening of action potential Lidocaine, Mexiletine, Tocainide, Phenytoin, Aprindine... 

Ventricular fibrillation should be terminated by electrical defibrillation. Alternatively, lidocaine can be injected intravenously. In cases with lower frequency, ventricular tachyarrhythmia class I diugs such as aj marine, flecainide or propafenone are more effective as a result of the use-dependence of lidocaine. For prophylaxis treatment, amiodarone or sotalol may be helpful or the implantation of a cardioverter-defibrillator system. Acute amiodarone (i.v. in higher doses) can also terminate ventricular tachyarrhythmias. This action, however, seems to be mediated by its INa-blocking side effects and not (or less) by its class III like effects. 

Lidocaine (Xylocaine), die representative class I-B drug, raises the threshold of the ventricular myocardium. Threshold is a term applied to any stimulus of the lowest intensity that will give rise to a response in a nerve fiber. A stimulus must be of a specific intensity (strength, amplitude) to pass along a given nerve fiber (Fig. 40-2). 

Another topical anesthetic, similar to benzocaine, is lidocaine, which is used to relieve the pain of shingles (herpes zoster) infections. Lidocaine is called an amide anesthetic, because it is not an ester (the alcohol is replaced by an amide, the nitrogen group). Amide anesthetics are metabolized by the liver, and are less prone to cause allergic reactions. If an anesthetic has the letter i in the prefix (lidocaine, prilocaine, bupivacaine), it is an amide anesthetic. 

Lidocaine (112), xyloceiine, and dibucaine (113) have been formulated in homo- and copolymers of lactide and glycolide. The goal of these studies has been relatively short-term (24-hr) controlled release of the anesthetic. Injectable microcapsules of lidocaine hydrochloride were produced by an air suspension coating technique and administered i.m. to rabbits (112). Serum levels of Udocaine indicated an initial rise over the first 2 hr and then a gradual decline with clearance after about 8-10 hr. 

FIG. 1 Molecular structures of the drugs examined in the delivery study the general anesthetics, alkanols (I), halothane (II), enflurane (III), isoflurane (IV), halogenated cyclobutane (V) the local anesthetics, dibucaine hydrochloride (VI), procaine hydrochloride (VII), tetracaine hydrochloride (VIII), lidocaine hydrochloride (IX), benzyl alcohol (X) the endocrine disruptor, bisphenol A (XI), and alkylbenzenes, benzene (XII), toluene (XIII), ethylbenzene (XIV), and propylbenzene (XV). 

The quinolinone derivative, OPC-88117 (73), is yet another compound described as possessing both Class I and Class III electrophysiological activities. Studies in guinea-pig papillary muscle showed that OPC-88117 at 30 increased APDgo by about 15% and decreased F ,ax by only 4% however, at 100 /iM APDgo was prolonged by 23 % and was decreased by 23 % [206]. Further experiments in isolated rabbit hearts demonstrated that OPC-88117 increased atrio-His bundle (A-H) and His bundle-ventricle (H-V) conduction times and refractory periods with a profile that was similar to, but more potent than that of lidocaine [207]. 

Can be considered oral lidocaine antidysrhythmic drugs have not been shown to improve survival in patients with ventricular dysrhythmias class I antidysrhythmic drugs (e.g., tocainide) have increased the risk of death when used in patients with nondife-threatening dysrhythmias... 

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