Proarrhythmic effects

Sotalol is rapidly and almost completely (>90%) absorbed. Bioavahabhity of absorbed dmg is 89—100%. Peak plasma levels are achieved in 2—4 h. Sotalol is 50% bound to plasma proteins. Plasma half-life of the compound is about 5.2 h. No metabolites of sotalol have been identified indicating littie metabolism. The dmg is excreted mainly by the kidneys (80—90%) and about 10% is eliminated in the feces. The plasma half-life is prolonged in patients having renal failure. Kinetics of the compound are not affected by changes in liver function (1,2). Sotalol has ah the adverse effects of -adrenoceptor blockers including myocardial depression, bradycardia, transient hypotension, and proarrhythmic effects (1,2). 

Class IC antiarrhythmic drugs such as flecainide or propafenone block the Na+ channel (open state propafenone open and inactivated state) with a very long dissociation time constant so that they alter normal action potential propagation. Flecainide increased mortality of patients recovering from myocardial infarction due to its proarrhythmic effects (CAST study). Action potential is shortened in Purkinje fibres but is prolonged in the ventricles. 

In high concentrations it blocks calcium channels and, thus, exerts prominent negative inotropic effects. Its adverse effects include proarrhythmic effects, worsening of heart failure and (due to (3-adrenoceptor blockade) bradycardia and bronchospasm. 

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

Following acute exposure to cyclodiene organochlorine pesticides, seizures and respiratory depression may occur (Ellenhom 1988 Proctor et al. 1988). Benzodiazepines (e.g., diazepam or lorazepam) or other anticonvulsant medications (e.g., phenobarbital) have been commonly used to control seizures (Ford 1993). Organochlorines may sensitize the myocardium to the proarrhythmic effects of adrenergic amines, potentially resulting in initiation of ventricular fibrillation (TOMES 1994). 

Sheridan, D.J. (2000) Drug-induced proarrhythmic effects assessment of... 

Proarrhythmic effects Antiarrhythmic agents may cause new or worsened arrhythmias. It is essential that each patient be evaluated electrocardiographically and clinically prior to and during therapy to determine whether the response to the drug supports continued treatment. ... 

Treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that are judged to be life-threatening. Because of the proarrhythmic effects, use with lesser arrhythmias is generally not recommended. 

Proarrhythmic effects Because of the proarrhythmic effects, use with lesser arrhythmias is generally not recommended. 

Because of the proarrhythmic effects of propafenone, reserve its use for patients in whom the benefits of treatment outweigh the risks. The use of propafenone is not recommended in patients with less severe ventricular arrhythmias, even if the patients are symptomatic. 

Proarrhythmic effects Propafenone may cause new or worsened arrhythmias. Such proarrhythmic effects range from an increase in frequency of PVCs to the development of more severe ventricular tachycardia, ventricular fibrillation or torsade de pointes, which may lead to fatal consequences. It is essential that each patient be evaluated electrocardiographically and clinically prior to, and during therapy to determine whether response to propafenone supports continued use. Non-life-threatening arrhythmias Use of propafenone is not recommended in patients with less severe ventricular arrhythmias, even if the patients are symptomatic. 

Ventricular proarrhythmic effects in patients with atrial fibrillation/flutter A review of the world literature revealed reports of 568 patients treated with oral flecainide for paroxysmal atrial fibrillation/flutter (PAF). Ventricular tachycardia was experienced in 0.4% of these patients. Of 19 patients in the literature with chronic atrial fibrillation (CAF), 10.5% experienced ventricular tachycardia (VT) or ventricular fibrillation (VF). Flecainide is not recommended for use in patients with CAF. Case reports of ventricular proarrhythmic effects in patients treated with flecainide for atrial... 

Proarrhythmic effects Flecainide can cause new or worsened arrhythmias. Such proarrhythmic effects range from an increase in frequency of PVCs to the development of more severe ventricular tachycardia. 

QTproiongation and potentiai for proarrhythmic effects In single dose studies of apomorphine, changes in QTc ranging from 0 to 7 msec were reported. Some drugs that prolong the QT/QTc interval have been associated with the occurrence of torsades de pointes and with sudden unexplained death. 

Chezalvielguilbert, F., Davy, J.M., Poirier, J.M. and Weissenburger, J. (1995) Mexiletine antagonizes effects of sotalol on qt interval duration and its proarrhythmic effects in a canine model of torsade-de-pointes. Journal of the American Collie of Cardiology, 26, 787—792. 

Blocker therapy has been shown to reduce post-myocardial infarction mortality by approximately 20% and is well accepted as a part of the postinfarction therapeutic regimen. In patients without any organic heart disease, a proarrhythmic effect is less common, and Class I agents may be safe and effective for the suppression of symptomatic VPC. 

Side effects of sotalol include those attributed to both P-adrenoceptor blockade and proarrhythmic effects. This arrhythmia is a serious threat, as it may lead to ventricular fibrillation. Adverse effects attributable to its p-blocker activity include fatigue, dyspnea, chest pain, headache, nausea, and vomiting. 

ET FDA Black Box OBRA regulated in U.S. Long Term Care Proarrhythmic effects... 

Ventricular proarrhythmic effects have been observed in patients with atrial fibril-lation/flutter. This drug is not recommended in patients with chronic atrial fibrillation. 

Because of proarrhythmic effects, not recommended for non-life threatening arrhythmias... 

Because of proarrhythmic effects demonstrated in CAST trials, this agent should be used only in patients with life-threatening arrhythmias. 

Mosapride is a selective 5-HT receptor agonist which is free from the extrapyramidal and proarrhythmic effects. It stimulates... 

Lidocaine is one of the least cardiotoxic of the currently used sodium channel blockers. Proarrhythmic effects, including sinoatrial node arrest, worsening of impaired conduction, and ventricular arrhythmias, are uncommon with lidocaine use. In large doses, especially in patients with preexisting heart failure, lidocaine may cause hypotension—partly by depressing myocardial contractility. 

Dhein S, Muller A, Gerwin R, Klaus W Comparative study on the proarrhythmic effects of some antiarrhythmic agents. Circulation 1993b 87 617—630. 

Isolated heart Not investigated Arrhythmias (coronary ligation) proarrhythmic effect Banning and Curtis, 1994... 

In contrast with observation on the guinea pig, histamine H3-receptors do not modulate noradrenaline release evoked by bilateral stimulation of stellate ganglia (Levi, personal communication), while their activation by endogenous histamine in an ischemia-reperfusion model resulted in a proarrhythmic effect, antagonised by thioperamide (Banning and Curtis, 1994). Also on this study an exogenous agonist was not tested. 

An initial increase in cardiac arrhythmias (proarrhythmic effect) may occur when class III drugs are instituted. The most important proarrhythmia is known as torsades de pointes, which is a form of ventricular tachycardia that can be fatal.11,40 Specific class III agents are associated with various other side effects. Amiodarone, for example, is associated with pulmonary toxicity and liver damage. Other class III drugs may have a more favorable side-effect profile but may not be as effective as amiodarone in controlling arrhythmias. Side effects of class HI drugs there-... 

Cardiac proarrhythmic effects of flecainide include aggravation of ventricular arrhythmias and threat of sudden death... 

Proarrhythmic effects of antiarrhythmic drugs In the Cardiac Arrhythmia Suppression Trial (CAST) treatment with encainide and flecainide, two class IC antiarrhythmic agents, successfully prevented ventricular ectopic beats in patients who had myocardial infarction. However, continued therapy with either drug was associated with a two- to three-fold increase in death due to cardiac arrhythmias. Similar results were reported for moricizine. Increased death was probably due to drug-induced fatal arrhythmias triggered by recurrent myocardial ischemia. 

Studenik C, Lemmens-Gruber R, Heistracher P (1999) Proarrhythmic effects of antidepressants and neuroleptic drugs on isolated, spontaneously beating guinea pig Purkinje fibers. Eur J Pharm Sci 7 11-118... 

Drug-Induced Proarrhythmic Effects in Dogs with Chronic AV Ablation... 

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