For ventricular arrhythmias

Propafenone. Propafenone hydrochloride, an arylketone, is stmcturaHy similar to the P-adrenoceptor blocking agents. It has been in use in the former West Germany since 1977 and was introduced in the United States in 1990. Its effects may result from a combination of weak calcium channel blocking, weak nonselective -adrenoceptor blocking, and sodium channel blocking activity. Propafenone is effective in treating supraventricular tachyarrhythmias, ventricular ectopic beats, and ventricular arrhythmias. It is the most frequendy prescribed medication for ventricular arrhythmias in Europe (32). 

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. 

Type Ic drugs profoundly slow conduction velocity while leaving refractoriness relatively unaltered. Although effective for both ventricular and supraventricular arrhythmias, their use for ventricular arrhythmias has been limited by the risk of proarrhythmia. 

Usual maintenance dose for atrial fibrillation is 200 mg/day (may further decrease dose to 100 mg/day with long-term use if patient clinically stable in order to decrease risk of toxicity) usual maintenance dose for ventricular arrhythmias is 300-400 mg/day. 

Cardiac effects Telithromycin has the potential to prolong the QTc interval in some patients. QTc prolongation may lead to an increased risk for ventricular arrhythmias, including torsades de pointes. 

Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter automatic defibrillator implantation trial investigators. N EnglJ Med.Dec 26 1996 335(26) 1933-1940. 

Tricyclic antidepressants are cardiotoxic, inducing tachycardias and an increased tendency for ventricular arrhythmias with high doses. This dose dependent cardiotoxicity gives these agents a low therapeutic index. Overdoses are characterized by cardiac conduction disturbances, hyperpyrexia, hypertension, confusion, hallucinations, seizures and coma and there is a high mortality rate in suicide attempts. Depressed patients should therefore not be given more than one week supply of these drugs. 

The first implantable cardioverter-defibrillator (ICD) was placed in 1982. Since that time, their use has expanded exponentially. Several large clinical trials have demonstrated the superiority of ICDs compared with pharmacological therapy for the secondary prevention of arrhythmic death and possibly as primary therapy for patients at risk for ventricular arrhythmias. 

I. ink MS et al. Antiarrhythmic drug therapy for ventricular arrhythmias Current perspectives. J Cardiovasc Electrophys 1996 7 653-670. 

Sotalol -Adrenergic blocker, direct action potential prolongation properties, use for ventricular arrhythmias, atria fibrillation... 

Liperoti R, Gambassi G, Lapane KL, Chiang C, Pedone C, Mor V, Bernabei R. Conventional and atypical antipsychotics and the risk of hospitalization for ventricular arrhythmias or cardiac arrest. Arch Intern Med 2005 165 696-701. 

Dose. For local anaesthesia, the total dose of lignocaine hydrochloride by injection should not exceed 300 mg (4.5 mg/kg), unless administered with adrenaline. For ventricular arrhythmias, initally 50 to 100 mg intravenously, followed by an infusion. 

The simultaneous administration technique was used to study a 64-year-old man with a creatinine clearance of 79 mL/ min who was started on N-acetyl-procainamide (NAPA) therapy for ventricular arrhythmias (see Figure 4.4). The oral NAPA dose was 66% absorbed in this patient, compared to 91.6 9.2% when this method was used to assess NAPA absorption in normal subjects. Although this approach is ideally suited for studies of drug absorption in various patient populations, the required additional chemical synthesis of stable isotope-labeled drug and mass spec-trometric analysis of patient samples have precluded its widespread adoption. 

Mexiletine is similar to lignocaine (lidocaine) but is effective by the oral route (t) 10 h). It has been used for ventricular arrhythmias especially those complicating myocardial infarction. The drug is usually poorly tolerated. Adverse reactions are almost universal and dose-related and include nausea. 

Zimmermann M. Antiarrhythmic therapy for ventricular arrhythmias. J Cardiovasc Pharmacol 1991 17(Suppl 6) S59-64. 

Myburgh DP, Goldman AP, Schamroth JM. Lorcainide— an anti-arrhythmic agent for ventricular arrhythmias. S Afr Med J 1980 57(7) 236-9. 

Stein J, Podrid PJ, Lampert S, Hirsowitz G, Town B. Longterm mexiletine for ventricular arrhythmia. Am Heart J 1984 107(5 Pt 2) 1091-8. 

Winkle RA, Meffin PJ, Harrison DC. Long-term tocainide therapy for ventricular arrhythmias. Circulation 1978 57(5) 1008-16. 

Qinical use Oniy for ventricular arrhythmias. Lidocaine is also used as a local anesthetic. 

B Because this patient has asthma and is wheezing, calcium channel blockers are the drug class of choice. Unlike beta-blockers and adenosine, they do not cause bronchospasm. Beta-blockers and adenosine should be used cautiously in patients with obstructive lung disease, and use should be avoided in patients with asthma. Digoxin is not contraindicated, but it is not the drug of choice due to its slow onset. Amiodarone is indicated for ventricular arrhythmias, but not PSVT. 

Wijnberg I D 2001 Phenytoin sodium per os as a treatment for ventricular arrhythmia in the horse. In Proceedings of the 40th British Equine Veterinary Association Congress, Harrogate, UK, p. 218... 

In addition to drugs in these classes, others may be used for certain arrhythmias. Digoxin may be used for treatment of atrial fibrillation, adrenaline for asystolic cardiac arrest, atropine for sinus bradycardia, methacholine (rarely) for supraventricular tachycardia, magnesium salts for ventricular arrhythmias, and calcium salts for ventricular arrhythmia due to hyperkalaemia. 

Answer E. Increased sympathetic activity is a major problem in hyperthyroidism and is best managed by use of beta blockers, which can offset cardiac stimulatory effects. Propranolol has an ancillary action in thyrotoxicosis in that it prevents conversion of T4 to T3 via its inhibition of 5 deiodinase. Amiodarone causes difficult-to-predict adverse effects on thyroid function and would not be appropriate in a patient with hyperthyroidism. Bretylium is an IV agent reserved for ventricular arrhythmias. Digoxin is not ideal because of its complex actions on the heart, which include both inhibition and stimulation. 

Kalahasti V, Nambi V, Martin DO, et al. QRS duration and prediction of mortality in patients undergoing risk stratification for ventricular arrhythmias. Am J Cardiol 2003 92(7) 798-803. 

Two new IC compounds should be mentioned. Propafenone (Rhythmol) (No. 14), introduced in the United States in 1989, has the structural components to be a (3-blocker. It is a weak one. It also possesses Ca2+ blocking properties and slows conduction in the atria and ventricles, the node between them, and the Purkinje-His areas. This earns the drug IC status. Over 80% of first-pass metabolism following oral absorption gives it poor bioavailability. Nevertheless, it is used orally as well as IV for ventricular arrhythmias. 

In practice, the only antiseizure drug that has been used in cardiac arrhythmias is phenytoin, which has characteristics similar to group IB antiarrhythmic dmgs. Phenytoin has been used for arrhythmias resulting from cardiac glycoside overdose and for ventricular arrhythmias unresponsive to lidocaine. 

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