Tocainide Lidocaine

Chabal C, Russell LC, Burchiel KJ 1989 The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain 38 333—338... 

Tocainide (Tonocard) (Fig. 26.11) is an a-methyl analogue structurally related to monoethylglycinexylide, the active metabolite of lidocaine, which possesses very similar electrophysiologic effects to lidocaine. In contrast to lidocaine, tocainide is orally active, and its oral absorption is excellent. Like lidocaine, it usually is reserved for the treatment of ventricular arrhythmias. The a-methyl group is believed to slow the rate of metabolism and, thereby, to contribute to oral activity. The plasma half-life of tocainide is approximately 12 hours, and nearly 50% of the drug may be excreted unchanged in the urine. Adverse effects associated with tocainide are like those observed with lidocaine—specifically, gastrointestinal disturbances and central nervous system effects. 

Foirence E, Covinsky JO, Mullen C. A seizure induced by concurrent lidocaine-tocainide therapy — Is it just a case of additive toxicity Drug Intell Clin Pharm (1986) 20, 56-9. 

Tocainide. Tocainide is a po active primary amine analogue of lidocaine. It consists of the (3)-(—) and the more active (R)-(+) enantiomers. 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

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

Many local anesthetics have a selective depressant action on heart muscle when given systemically. This is useful in treatment of cardiac arrhythmias, and a lidocaine-like drug with this kind of action is tocainide (2). ... 

IB (tocainide, lidocaine, phenytoin, mexiletine) - Depress phase 0 slightly and may shorten the action potential duration. Although arrhythmia is not a labeled indication for phenytoin, it is commonly used in treatment of digitalis-induced arrhythmias. 

Drugs that may affect lidocaine include beta-blockers, cimetidine, procainamide, tocainide, and succinylcholine. 

IB Lidocaine Phenytoin Tocainide Moricizine Mexiletine Minimally change V , of phase 0, decrease cardiac action potential duration, decrease inward sodium current in ventricular muscle, increase outward potassium current. 

Tocainide (Tonocard) is an orally effective antiarrhyth-mic agent with close structural similarities to 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. 

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... 

Since local anesthetics have membrane-stabilizing effects, both parenteral (eg, intravenous lidocaine) and oral (eg, mexiletine, tocainide) formulations of local anesthetics have been used to treat patients with neuropathic pain syndromes because these syndromes are thought to involve uncontrolled, rapid, sensory fiber firing. Systemic local anesthetic drugs are commonly used as adjuvants to the combination of a tricyclic antidepressant (eg, amitriptyline) and an anticonvulsant (eg, carbamazepine) in chronic pain patients who fail to respond to the combination of antidepressant and anticonvulsant. 

CkH,, N 87-62-7) see Bupivacaine Htidocainc Lidocaine Lidoflazine Mepivacainc Pilstcainide Pyrrocaine Ropivaeaine hydrochloride Tocainide Xipamidc... 

Lidocaine, mexiletine and tocainide block open or inactivated sodium channels. These drugs have a rapid rate of association with sodium channels. 

These are Class IB drugs with actions similar to those of lidocaine. These agents can be administered orally. Mexiletine [mex IL e teen] is used for chronic treatment of ventricular arrhythmias associated with previous myocardial infarction. Tocainide [toe KAY nide] is used for treatment of ventricular tachyarrhythmias. Tocainide has pulmonary toxicity, which may lead to pulmonary fibrosis. 

Mechanism of action. Na -channel blocking antiarrhythmics resemble most local anesthetics in being cationic amphiphilic molecules (p.206 exception phenytoin, p.191). Possible molecular mechanisms of their inhibitory effects are outlined on p.202 in more detail. Their low structural specificity is reflected by a low selectivity toward different cation channels. Besides the Na channel. Carotid 1C channels are also likely to be blocked. Accordingly, cationic amphiphilic antiarrhythmics affect both the depolarization and repolarization phases. Depending on the substance, AP duration can be increased (Class IA), decreased (Class IB), or remain the same (Class IC). Antiarrhythmics representative of these categories include Class IA—quinidine, procainamide, ajmaline, disopyramide Class IB—lidocaine, mexile-tine, tocainide Class IC—flecainide, propafenone. 

Greenspon AJ, Mohiuddin S, Saksena S, Lengerich R, Snapinn S, Holmes G, Irvin J, Sappington E, et al. Comparison of intravenous tocainide with intravenous lidocaine for treating ventricular arrhythmias. Cardiovasc Rev Rep 1989 10 55-9. 

Arthralgia has been reported in two cases with positive antinuclear antibody titers, suggesting the possibility of a lupus-like syndrome (37). In another case tocainide treatment was associated with both a lupus-like syndrome and neutropenia (38). Cross-reactivity of tocainide with lidocaine has been reported (39). 

Duff HJ, Roden DM, Marney S, Colley DG, Maffucci R, Primm RK, Oates JA, Woosley RL. Molecular basis for the antigenicity of lidocaine analogues tocainide and mexiletine Am Heart J 1984 107(3) 585-9. 

Other agents Tocainide and mexiletine are analogues of lidocaine vuth improved oral bioavailability. 

Absorption Lidocaine is ineffective orally 60% to 70% of an oral dose is metabolized by the liver before reaching the systemic circulation. It is only administered IVfor arrhythmias. Both mexiletine and tocainide are well absorbed orally. 

Adverse reactions Minor side effects of lidocaine are drowsiness, dizziness, paresthesia, and euphoria. More serious side effects include CNS and cardiovascular effects. Tocainide and mexiletine both have a high incidence of Gl side effects (nausea and vomiting) and CNS side effects (dizziness, numbness, and paresthesias). Additionally, tocainide has a 15% incidence of rash and may cause agranulocytosis. 

Mexiletine Hydrochloride. Mcxiletinc hydrochloride. l-methyl-2-(2.6-xylyloxy)cthylamine hydrochloride (Mexi-til) (pK.., 8.4), is a class IB ontiarrhythniic agent that is cffec-tive when given either intravenously or orally. It re.sembles lidocaine in po.ssessing a xylyl moiety but otherwise is diTfer-ent chemically. Mexiletine hydrochloride is an ether and is not subject to the hydrolysis common to the amides lidocaine and tocainide. Its mean half-life on oral administration is approximately 10 hours. 

Tocainide, proprietary name Tonocard, has electrophysiolog-ical properties similar to lidocaine. It is useful in the management of ventricular arrhythmias typified by a prolonged QT interval. Tocainide has the advantage over lidocaine in that it can be taken orally, and it has a relatively long half-life (13 to 16 hours). Optimal response to tocainide... 

Congestive heart failure and uremia reduce renal clearance and the volume of distribution and increase the clearance half-life. Tocainide is not highly protein bound, so it does not exhibit die protein-binding phenomenon described for lidocaine after myocardial infarction. Clinically, the dose should be reduced proportionally to glomerular filtration to maintain therapeutic levels. 

Na+ Anticonvulsant drugs Class I antiarrhythmics Diuretic drugs Local anesthetic drugs Carbamazepine, phenytoin, valproic acid lA Disopyramide, procainamide, quinidine IB Lidocaine, mexiletine, phenytoin, tocainide IC Encainide, flecainide, propafenone Amiloride Bupivacaine, cocaine, lidocaine, mepivacaine, tetracaine... 

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