Tocainide adverse effects

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. 

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. 

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). 

Gass IB drugs are less state-dependent blockers of fast Na+ channels, and they decrease the APD. The uses for lidocaine, mexiletine, and tocainide are discussed, as are the metabolism and adverse effects of lidocaine. 

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. 

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). 

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. 

Discuss the onset of adverse hematological effects seen with tocainide therapy. 

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