Lidocaine channel inhibition

Illyin, V.I. Comparative study of inhibition ofhSkMI sodium channels by Co102862, lidocaine and bupivacaine, Biophysical. J. 1999, 76, A82. 

Recently, specific binding to sodium channels was demonstrated for the state-dependent sodium channel blocker [3H]BPBTS [105]. BPBTS is a potent blocker of all sodium channel subtypes tested, including native TTX-resistant channels expressed in mouse sensory neurons. Binding of [3H]BPBTS is inhibited by the local anesthetics tetracaine and lidocaine at concentrations known to interact with channels in the open and/or inactivated state. 

The sodium-channel inhibitor Amiloride is used for the treatment of chronic bronchitis, and the most frequently used anesthetic drug, lidocain, inhibits voltagegated sodium-channel a subunits, which mediate the pathophysiology of pain. 

The antiarrhythmic of choice for SuVT is lidocaine because of its fast onset and ease of administration. Lidocaine is a class IB antiarrhythmic that inhibits sodium ion channels, decreasing the action potential duration and effective... 

Lidocaine combines with fast voltage-gated sodium channels and inhibits recovery after repolarization. As a result, cellular conduction is blocked by... 

Answer A. Amiodarone is a highly effective antiarrhythmic drug, in part because of its multiple actions, which include Na channel block, beta adrenoceptor block, K channel block, and Ca channel block. Drugs that block channels (which include class lA and class III antiarrhythmics) prolong APD and ERP and predispose toward torsades de pointes ventricular arrhythmias. Flecamide is a class IC drug, lidocaine and phenytoin are class IB, and verapamil is class IV, none of which inhibits the delayed rectifier K+ current responsible for membrane repolarization during the cardiac action potential. 

Lidocaine [2-(diethylamino)-N-(2, 6-dimethylphenyl) acetamide monohydrochloride] is the most commonly used amino amide-type local anesthetic. Lidocaine is very lipid soluble and, thus, has a more rapid onset and a longer duration of action than most amino ester-type local anesthetics, such as procaine and tetracaine. It can be administered parenterally (with or without epinephrine) or topically either by itself or in combination with prilocaine or etidocaine as a eutectic mixture that is very popular with pediatric patients. The use of lidocaine-epinephrine mixtures should be avoided, however, in areas with limited vascular supply to prevent tissue necrosis. Lidocaine also frequently is used as a class IB antiarrhythmic agent for the treatment of ventricular arrhythmias, both because it binds and inhibits sodium channels in the cardiac muscle and because of its longer duration of action than amino ester-type local anesthetics. 

A. Cimetidine, and to a lesser extent ranitidine, reduces hepatic clearance and prolongs the elimination half-life of several dmgs as a result of inhibition of cytochrome P-450 activity and reduction of hepatic blood flow. Examples of drugs affected include phenytoin, theophylline, phenobatbital, cyclosporine, morphine, lidocaine, calcium channel blockers, tricyclic antidepressants, and warfarin. 

Lidocaine, like other local anesthetics, binds axonal membrane voltage-gated fast Na channels and thus prevents Na+ transport across the channels, thus inhibiting cell membrane depolarization. It is by this same mechanism that lidocaine exerts its effect as a class Ib antiarrhythmic to inhibit cardiac smooth muscle excitability and as an anti-epileptic drug to inhibit cortical excitability. Its lipophilic aromatic group allows the molecule to penetrate the nerve membrane, while its hydrophilic charged amine group is the portion of the molecule that actually binds the Na chaimel [1-3]. 

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