Antiarrhythmics adverse effects

Monitor patients for adverse effects of antiarrhythmic drugs administered (Table 6-6). 

Indications. Verapamil is used as an antiarrhythmic drug in supraventricular tachyarrhythmias. In atrial flutter or fibrillation, it is effective in reducing ventricular rate by virtue of inhibiting AV-conduction. Verapamil is also employed in the prophylaxis of angina pectoris attacks (p. 308) and the treatment of hypertension (p. 312). Adverse effects Because of verapamil s effects on the sinus node, a drop in blood pressure fails to evoke a reflex tachycardia Heart rate hardly changes bradycardia may even develop. AV-block and myocardial insufficiency can occur. Patients frequently complain of constipation. 

Mechanism of action, as adverse effects can be associated with desired effects, for example, antiarrhythmic agents can be proarrhythmic in some circumstances. 

Keep patient supine during therapy or closely observe for postural hypotension. The optimal dose has not been determined. Dosages greater than 40 mg/kg/day have been used without apparent adverse effect. As soon as possible, and when indicated, change patient to an oral antiarrhythmic agent for maintenance therapy. Immediate life-threatening ventricular arrhythmias (eg, ventricular fibrillation, hemodynamically unstable ventricular tachycardia) Administer undiluted, 5 mg/kg by rapid IV injection. If ventricular fibrillation persists, increase dosage to 10 mg/kg and repeat as necessary. 

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. 

Quinidine is readily absorbed from the GI tract and eliminated by hepatic metabolism. It is rarely used because of cardiac and extracardiac adverse effects and the availability of better-tolerated antiarrhythmic drugs. 

In the USA, amiodarone is approved for oral and intravenous use to treat serious ventricular arrhythmias. However, the drug is also highly effective for the treatment of supraventricular arrhythmias such as atrial fibrillation. As a result of its broad spectrum of antiarrhythmic action, it is very extensively used for a wide variety of arrhythmias. Amiodarone has unusual pharmacokinetics and important extracardiac adverse effects. Dronedarone, an analog that lacks iodine atoms, is under investigation. 

In some types of rhythm disorders, antiar-rhythmics of the local anesthetic, Na+-channel blocking type are used for both prophylaxis and therapy. These substances block the Na+ channel responsible for the fast depolarization of nerve and muscle tissues. Therefore, the elicitation of action potentials is impeded and impulse conduction is delayed. This effect may exert a favorable influence in some forms of arrhythmia, but can itself act arrhythmogenically. Unfortunately, antiarrhythmics of the local anesthetic, Na+-channel blocking type lack suf -cient specificity in two respects (1) other ion channels of cardiomyocytes, such as K1 and Ca+ channels, are also affected (abnormal QT prolongation) and (2) their action is not restricted to cardiac muscle tissue but also impacts on neural tissues and brain cells. Adverse effects on the heart include production of arrhythmias and lowering of heart rate, AV conduction, and systolic force. CNS side effects are manifested by vertigo, giddiness, disorientation, confusion, motor disturbances, etc. 

CIMETIDINE, RANITIDINE ANTIARRHYTHMICS-AMIODARONE, FLECAINIDE, MEXILETINE, PROCAINAMIDE, PROPAFENONE Likely t plasma concentrations of these antiarrhythmics and risk of adverse effects Cimetidine inhibits CYP2D6-mediated metabolism of flecainide, mexiletine, procainamide and propafenone. Ranitidine is a much weaker CYP2D6 inhibitor. Cimetidine is a potent inhibitor of organic cation transport in the kidney, and the elimination of procainamide is impaired Monitor PR and BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider alternative acid suppression therapy... 

Schwartz JB, Keefe D, Harrison DC. Adverse effects of antiarrhythmic drugs. Drugs 1981 21(1) 23 5. 

Wooten JM, Earnest J, Reyes J. Review of common adverse effects of selected antiarrhythmic drugs. Crit Care Nurs Q 2000 22(4) 23-38. 

Ellrodt G, Singh BN. Adverse effects of disopyramide (Norpace) toxic interactions with other antiarrhythmic agents. Heart Lung 1980 9(3) 469-74. 

Murray KT, Barbey JT, Kopelman HA, Siddoway LA, Echt DS, Woosley RL, Roden DM. Mexiletine and tocai-nide a comparison of antiarrhythmic efficacy, adverse effects, and predictive value of lidocaine testing. Clin Pharmacol Ther 1989 45(5) 553-61. 

---