Antiarrhythmic agents lidocaine

The only other anesthetic to cause serious toxicity for which a metabolic drug interaction has been reasonably well characterized is the local anesthetic and antiarrhythmic agent lidocaine. Amiodarone decreased lidocaine systemic clearance in a patient (primarily by inhibition of CYP3A4 N-dealkylation of lidocaine) and yielded concentrations of lidocaine that led to seizures (78,79). 

A recent study has employed deuterium labeling to show that the mechanism for the oxidative N-demethylation of nicotine may involve two modes of breakdown for a proposed carbinolamine intermediate, dealkylation with formaldehyde formation and dehydration to an iminium ion.72 The formation of such an sp2-hybrid intermediate may help to explain why both a primary and substantial / -secondary deuterium isotope effect were observed for the N-deethylation of the antiarrhythmic agent, lidocaine.73 In contrast, only a primary isotope effect was observed on the rate of oxidative O-deethylation of deuterated analogs of the analgesic, phenacetin. 77 These results indicate differences in the mechanism of oxidative 0- and N-dealkylation. A final example of the use of secondary deuterium isotope effects in studying enzymes involved in drug metabolism revealed an SN-2-like transition state for the transfer of a methyl group catalyzed by catechol-O-methyl transferase.73... 

In the treatment of life-threatening ventricular arrhythmias (ie, ventricular tachycardia) which have failed to respond to first-line antiarrhythmic agents (eg, lidocaine). 

Mexiletine (Mexitil) is an antiarrhythmic agent with pharmacological and antiarrhythmic properties similar to those of lidocaine and tocainide. Like tocainide, mexiletine is available for oral administration. 

Lidocaine hydrochloride Xylocaine) is the most commonly used local anesthetic. It is well tolerated, and in addition to its use in infiltration and regional nerve blocks, it is commonly used for spinal and topical anesthesia and as an antiarrhythmic agent (see Chapter 16). Lidocaine has a more rapidly occurring, more intense, and more prolonged duration of action than does procaine. 

Local anesthetics have weak direct neuromuscular blocking effects that are of little clinical importance. However, their effects on cardiac cell membranes are of major clinical significance, and some local anesthetics are widely used as antiarrhythmic agents (eg, lidocaine) (see Chapter 14) at concentrations lower than those required to produce nerve block. Others of the same amide class (eg, bupivacaine, ropivacaine) can cause lethal arrhythmias if high plasma concentrations are inadvertently achieved. 

The class lb antiarrhythmic drug mexilitine is structurally related to the local anesthetic agent lidocaine and also shows a voltage- and frequency-dependent block of sodium channels. Mexilitine is not selective for any painrelevant subtype of sodium channel. As an advantage over lidocaine, mexilitine can be given orally. 

As noted above, the antiarrhythmic drugs can modify impulse generation and conduction. More than a dozen such drugs that are potentially useful in treating arrhythmias are currently available. However, only a limited number of these agents are clinically beneficial in the treatment of selected arrhythmias. For example, the acute termination of ventricular tachycardia by lidocaine or supraventricular tachycardia by adenosine or verapamil are examples in which antiarrhythmic therapy results in decreased morbidity. In contrast, many of the antiarrhythmic agents are now known to have lethal proarrhythmic actions, that is, to cause arrhythmias. 

Amiodarone, lidocaine, and procainamide are commonly used antiarrhythmics for conversion in VF. Of these, amiodarone is the antiarrhythmic agent recommended first. In the Amiodarone versus Lidocaine in Ventricular Emergency (ALIVE) trial, patients administered amiodarone had a better rate of survival to hospital admission than those... 

Lidocaine (lignocaine) is a class Ib antiarrhythmic agent. Its antiarrhythmic action is mediated mainly within the non-nodal tissue of the ventricles and... 

A recommendation for a specific antiarrhythmic agent of first choice does not exist. Amiodarone, lidocaine, and procainamide are the available options. 

Ans A Lidocaine, a class IB drug, is the least likely antiarrhythmic agent... 

Lidocaine has a wide range of clinical uses as a local anesthetic it has utility in almost any application where a local anesthetic of intermediate duration is needed. Lidocaine also is used as an antiarrhythmic agent. 

Moricizine (600 to 900 mg/day given every 8 hours in three equally divided doses) is indicated in the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that are life threatening. Because of the proarrhythmic effects of moricizine, its use should be reserved for patients in whom the benefits of treatment outweigh the risks. Moricizine is a class 1C antiarrhythmic agent with potent local anesthetic activity and myocardial-membrane-stabilizing effects. It shares some of the characteristics of the class lA (disopyramide, procainamide, or quinidine), of class IB (lidocaine, mexiletene, phenytoin, or tocainide), or class 1C agents (encainide, flecainide, or propafenone) in that it reduces the fast inward current carried by sodium ions. Moricizine shortens phase 2 and 3... 

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. 

Local anesthetics are widely used to provide anesthesia via local subcutaneous Injection topical application to skin and mucous membranes and epidural, spinal, and regional nerve blocks. In addition, lidocaine (see p 462) is used intravenously as an antiarrhythmic agent and cocaine (see p 171) is a popular drug of abuse. Gommonly used agents are divided into two chemical groups ester-linked and amide-linked (Table 11-2). 

---