Verapamil ventricular arrhythmias

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

The answer is e. (Hardman, pp 858-874.) Because verapamil, a Ca channel blocker, has a selective depressing action on AV nodal tissue, it is an ideal drug for both immediate and prophylactic therapy of supraventricular tachycardia (SVT). Nifedipine, another Ca channel blocker, has little effect on SAT Lidocaine and adenosine are parenteral drugs with short ha If-lives and, thus, are not suitable for prophylactic therapy. Procainamide is more suitable for ventricular arrhythmias and has the potential for serious adverse reactions with long-term use. 

Maintenance dose 0.125-0.25 mg PO/IV qd low potassium or magnesium levels potentiate toxicity reduce dose in renal failure toxicity indicated by nausea, headache, visual disturbances (yellow-green halos), ventricular arrhythmias. Quinidine, verapamil, and amiodarone elevate digoxin level. 

Concomitant use of calcium channel blockers (atenolol) Bradycardia and heart block can occur and the left ventricular end diastolic pressure can rise when beta-blockers are administered with verapamil or diltiazem. Patients with preexisting conduction abnormalities or left ventricular dysfunction are particularly susceptible. Recent acute Ml (sotalol) Sotalol can be used safely and effectively in the long-term treatment of life-threatening ventricular arrhythmias following an Ml. However, experience in the use of sotalol to treat cardiac arrhythmias in the early phase of recovery from acute Ml is limited and at least at high initial doses is not reassuring. 

Supraventricular tachycardia is the major arrhythmia indication for verapamil. Adenosine or verapamil are preferred over older treatments (propranolol, digoxin, edrophonium, vasoconstrictor agents, and cardioversion) for termination. Verapamil can also reduce the ventricular rate in atrial fibrillation and flutter. It only rarely converts atrial flutter and fibrillation to sinus rhythm. Verapamil is occasionally useful in ventricular arrhythmias. However, intravenous verapamil in a patient with sustained ventricular tachycardia can cause hemodynamic collapse. 

These agents appear to be similar in efficacy to verapamil in the management of supraventricular arrhythmias, including rate control in atrial fibrillation. An intravenous form of diltiazem is available for the latter indication and causes hypotension or bradyarrhythmias relatively infrequently. Bepridil also has action potential- and QT-prolonging actions that theoretically may make it more useful in some ventricular arrhythmias but also create the risk of torsade de pointes. Bepridil is only rarely used, primarily to control refractory angina. 

CALCIUM CHANNEL BLOCKERS SERTINDOLE Plasma concentrations of sertindole are t by diltiazem and verapamil Diltiazem and verapamil inhibit CYP3A4-mediated metabolism of sertindole Avoid co-administration raised sertindole concentrations are associated with an t risk of prolonged Q-T interval and therefore ventricular arrhythmias, particularly torsades de pointes... 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

Adenosine is the treatment of choice for diagnosis and reversal of supraventricular arrhythmias. Verapamil is an alternative for the management of narrow complex tachycardias. Amiodarone is the most effective drug at reversing atrial fibrillation, and in prevention of ventricular arrhythmias, but has several adverse effects. 

Answer A. Amiodarone is a highly effective antiarrhythmic drug, in part because of its multiple actions, which include Na channel block, beta adrenoceptor block, K channel block, and Ca channel block. Drugs that block channels (which include class lA and class III antiarrhythmics) prolong APD and ERP and predispose toward torsades de pointes ventricular arrhythmias. Flecamide is a class IC drug, lidocaine and phenytoin are class IB, and verapamil is class IV, none of which inhibits the delayed rectifier K+ current responsible for membrane repolarization during the cardiac action potential. 

Ferrier GR, Sounders JH, Mendez C (1973) A cellular mechanism for the generation of ventricular arrhythmias by acetylstrophanthidin. Circ Res 32 600-609 Garvey HE (1969) The mechanism of action of verapamil on the sinus and AV nodes. Eur J Pharmacol 8 159-166... 

Most calcium antagonists do not affect intraventricular conduction, so the QRS duration is usually unaffected. The PR interval may be prolonged even with therapeutic doses of verapamil. Bepridil prolongs the QT interval and may cause ventricular arrhythmias, including torsade de pointes (see p 14). Mibefradil also causes QT prolongation, and has been associated with ventricular arrhythmias. It has been removed from the US market. 

Note that intravenous calcium compounds are sometimes given prior to intravenous verapamil for the treatment of ventricular arrhythmias to prevent verapamil-induced hypotension in situations where a reduction in blood pressure could be detrimental. This use does not affect the antiarrhythmic efficacy. Calcium, usually in the form of intravenous calcium gluconate, is used as an antidote in cases of overdose of calcium-channel blockers. 

Verapamil. Verapamil hydrochloride (see Table 1) is a synthetic papaverine [58-74-2] C2qH2 N04, derivative that was originally studied as a smooth muscle relaxant. It was later found to have properties of a new class of dmgs that inhibited transmembrane calcium movements. It is a (+),(—) racemic mixture. The (+)-isomer has local anesthetic properties and may exert effects on the fast sodium channel and slow phase 0 depolarization of the action potential. The (—)-isomer affects the slow calcium channel. Verapamil is an effective antiarrhythmic agent for supraventricular AV nodal reentrant arrhythmias (V1-2) and for controlling the ventricular response to atrial fibrillation (1,2,71—73). 

Verapamil is useful for slowing the ventricular response to atrial tachyarrhythmias, such as atrial flutter and fibrillation. Verapamil is also effective in arrhythmias supported by enhanced automaticity, such as ectopic atrial tachycardia and idiopathic left ventricular tachycardia. 

Make a firm diagnosis. A firm arrhythmia diagnosis should be established. For example, the misuse of verapamil in patients with ventricular tachycardia mistakenly diagnosed as supraventricular tachycardia can lead to catastrophic hypotension and cardiac arrest. As increasingly sophisticated methods to characterize underlying arrhythmia mechanisms become available and are validated, it may be possible to direct certain drugs toward specific arrhythmia mechanisms. 

As noted above, the antiarrhythmic drugs can modify impulse generation and conduction. More than a dozen such drugs that are potentially useful in treating arrhythmias are currently available. However, only a limited number of these agents are clinically beneficial in the treatment of selected arrhythmias. For example, the acute termination of ventricular tachycardia by lidocaine or supraventricular tachycardia by adenosine or verapamil are examples in which antiarrhythmic therapy results in decreased morbidity. In contrast, many of the antiarrhythmic agents are now known to have lethal proarrhythmic actions, that is, to cause arrhythmias. 

Quinidine [KWIN i deen] is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. Because of quinidine s toxic potential, calcium antagonists, such as verapamil, are increasingly replacing this drug in clinical use. 

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