Tocainide effects

Some rare toxic effects that may result from tocainide therapy are a lupus-fike syndrome, skin rash, pulmonary complications, and hematologic abnormalities, eg, agranulocytosis (1,2,24). 

These drug s are contraindicated in those with a known hypersensitivity to any component of the preparation. The topical anesthetics are used cautiously in patients receiving Class I antiarrhytiimic drug s such as tocainide and mexiletine because the toxic effects are additive and potentially synergistic. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

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

Tocainide is indicated for the treatment of symptomatic ventricular arrhythmias refractory to more conventional therapy. Serious noncardiac adverse effects limit its use to patients with life-threatening arrhythmias. 

Light-headedness, dizziness, or nausea occurs in approximately 15% of patients, paresthesias and numbness in 9%, and tremor in 8%. These adverse effects are generally mild in intensity, transient, and dose related. Overall, however, approximately 20% of patients prescribed tocainide discontinue therapy because of such effects. Serious immune-based side effects, such as pulmonary fibrosis, have been reported, and blood dyscrasias, such as agranulocytosis and thrombocytopenia, may occur in up to 0.2% of patients. 

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. 

TABLE 4 Effect of the Concentrations of Sulfuric Acids on the Chiral Resolution of Thyroxine and Tocainide... 

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. 

The negative inotropic effects of class I antidysrhythmic agents, such as disopyramide, procainamide, quinidine, and tocainide can be accentuated by beta-blockers this is most pronounced in patients with pre-existing myocardial disease and can result in left ventricular failure or even asystole (413). Digoxin can obviate the negative inotropic effect of beta-blockers in patients with poor left ventricular function. 

North DS, Mattern AL, Kapil RP, Lalonde RL. The effect of histamine-2 receptor antagonists on tocainide pharmacokinetics. J Clin Pharmacol 1988 28(7) 640-3. 

The clinical pharmacology, uses, efficacy, and adverse effects of tocainide have been extensively reviewed (1-9). 

The adverse effects of tocainide occur with increasing frequency above plasma concentrations of 10 pg/ml. They are mostly related to the nervous system. In two large series withdrawal of tocainide was required in 11-16% of patients because of adverse effects (10,11). The high incidence of blood dyscrasias severely hmits the use of tocainide. 

Adverse cardiovascular effects have been reported in 6-55% of cases. After a single dose of tocainide the most common effect is hypotension with bradycardia (12). Angina pectoris has also been reported (13). 

During repeated administration cardiovascular adverse effects are relatively uncommon. Increasing heart failure (14,15), worsening dysrhythmias (15,16), pericarditis (15,17,18), and sinus arrest with sinoatrial block (19) have all been reported. Tocainide can worsen ventricular tachycardia (20). 

Winkle RA, Anderson JL, Peters F, Meffin PJ, Fowles RE, Harrison DC. The hemodynamic effects of intravenous tocainide in patients with heart disease. Circulation 1978 57(4) 787-92. 

Nyquist O, Forssell G, Nordlander R, Schenck-Gustafsson K. Hemodynamic and antiarrhythmic effects of tocainide in patients with acute myocardial infarction. Am Heart J 1980 100(6 Pt 2) 1000-5. 

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. 

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... 

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