Lidocaine , antiarrhythmic

Traditional local anaesthetics (lidocaine), antiarrhythmics (mexiletine) and anticonvulsants (phenytoin), antipsychotics (carbamazepine) and anti-depressants (amitriptyline) have all been used clinically, with substantial interpatient... 

Lldoc ine. Lidocaine hydrochloride, an anilide, was originally introduced as a local anesthetic in 1943 and found to be a potent antiarrhythmic in 1960. The compound is a reverse amide of procainamide. Lidocaine is generally considered to be the dmg of choice in the treatment of ventricular arrhythmias and those originating from digitalis glycoside toxicity (1,2,15—17). 

Class IB drugs like lidocaine, phenytoin or mex-iletine preferentially bind to the inactivated state. Lidocaine, a local anaesthetic, can be used intravenously for antiarrhythmic treatment. It is one of the classical dtugs used in emergency medicine for the... 

State-dependent block describes the binding of a drug to a certain state of an ionic channel. Tims, the fast Na+ channel switches between a resting and open and inactivated states, the latter being the state to which antiarrhythmic drugs like lidocaine bind. 

Some cardiac arrhythmias result from many stimuli present in the myocardium. Some of these are weak or of low intensity but are still able to excite myocardial tissue Lidocaine, by raising the threshold of myocardial fibers, reduces the number of stimuli that will pass along these fibers and therefore decreases the pulse rate and corrects the arrhythmia Mexiletine (Mexitil) and tocadnide (Tonocard) are also antiarrhythmic drag s with actions similar to those of lidocaine... 

Patients with mild or no symptoms can be treated initially with antiarrhythmic drugs. IV amiodarone is now recommended as first-line therapy in this situation. Procainamide or lidocaine given IV is a suitable alternative. Synchronized DCC should be delivered if the patient s status deteriorates, VT degenerates to VF, or drug therapy fails. 

The typical form of proarrhythmia caused by the type Ic antiarrhythmic drugs is a rapid, sustained, monomorphic VT with a characteristic sinusoidal QRS pattern that is often resistant to resuscitation with cardioversion or overdrive pacing. Some clinicians have had success with IV lidocaine (competes for the sodium channel receptor) or sodium bicarbonate (reverses the excessive sodium channel blockade). 

The purpose of antiarrhythmic drug therapy after unsuccessful defibrillation and vasopressor administration is to prevent the development or recurrence of VF and PVT by raising the fibrillation threshold. However, the role of antiarrhythmics is limited because clinical evidence demonstrating improved survival to hospital discharge is lacking. Only amiodarone and lidocaine are recommended in the 2005 guidelines for CPR and ECC. 

Schwartz, M.L., Meyer, M.B., Covino, B.G. and Narang, R.M. (1974). Antiarrhythmic effectiveness of intramuscular lidocaine Influence of different injection sites. J. Clin. Pharmacol. 14 77-83. 

Codeine, dextromethorphan, haloperidol, thioridazine, perphenazine, nortriptyline, desipramine, fluoxetine, norfluoxetine, TCAs (hydroxylation), beta-blockers such as timolol and metoprolol, type 1C antiarrhythmics encainide, flecainide TCAs (desmethylation), triazolam, alprazolam, midazolam, carbamazepine, terfenadine, quinidine, lidocaine, erythromycin, cyclosporin... 

Lidocaine is a prototype of antiarrhythmic drugs of subgroup IB, and is widely used for treating and preventing ventricular ectopic activity during myocardial infarction. 

Replacement therapy-As soon as possible, change patient to IV lidocaine or to an oral antiarrhythmic preparation for maintenance therapy. However, if necessary, an additional IM injection may be administered after 60 to 90 minutes. 

Absorption/Distribution - Lidocaine is ineffective orally it is most commonly administered IV with an immediate onset (within minutes) and brief duration (10 to 20 minutes) of action following a bolus dose. Continuous IV infusion of lidocaine (1 to 4 mg/min) is necessary to maintain antiarrhythmic effects. Following IM administration, therapeutic serum levels are achieved in 5 to 15 minutes and may persist for up to 2 hours. Higher and more rapid serum levels are achieved by injection into the deltoid muscle. Therapeutic serum levels are 1.5 to 6 mcg/mL serum levels greater than 6 to 10 mcg/mL are usually toxic. Lidocaine is approximately 50% protein bound (concentration-dependent). 

Electrophysiology- Mexiletine is a local anesthetic and a Class IB antiarrhythmic compound with electrophysiologic properties similar to lidocaine. 

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

Transfer to sotalol from other antiarrhythmic therapy- Before starting sotalol, generally withdraw previous antiarrhythmic therapy under careful monitoring for a minimum of 2 to 3 plasma half-lives if the patient s clinical condition permits. Treatment has been initiated in some patients receiving IV lidocaine without ill effect. After discontinuation of amiodarone, do not initiate sotalol until the QT interval is normalized. 

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

It is difficult to suggest a mechanism for lidocaine s antiarrhythmic action on the basis of its effects on normal ventricular myocardial tissue and His-Purkinje tissue. 

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. 

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