Propafenone effects

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). 

I c With only little effect on action potential duration Lorcainide, Flecainide, Propafenone... 

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. 

Propafenone possesses (3-adrenoceptor antagonistic effects due to its structural similarity to propranolol. 

Ventricular fibrillation should be terminated by electrical defibrillation. Alternatively, lidocaine can be injected intravenously. In cases with lower frequency, ventricular tachyarrhythmia class I diugs such as aj marine, flecainide or propafenone are more effective as a result of the use-dependence of lidocaine. For prophylaxis treatment, amiodarone or sotalol may be helpful or the implantation of a cardioverter-defibrillator system. Acute amiodarone (i.v. in higher doses) can also terminate ventricular tachyarrhythmias. This action, however, seems to be mediated by its INa-blocking side effects and not (or less) by its class III like effects. 

During die initiation of therapy, patients taking propafenone must be monitored carefully. To minimize adverse reactions, dosage is increased slowly at a minimum of 3- to 4-day intervals. Periodic ECG monitoringis necessary to evaluate the effects on cardiac conduction. 

Inselmann G, Volkmann A, Heidemann H. Comparison of the effects of liposomal amphotericin B and conventional amphotericin B on propafenone metabolism and cytochrome P450 in rats. Antimicrob Agents Chemother 2000 44 131. 

C (flecainide, encainide, propafenone) - Marked depression of phase 0. Slight effect on repolarization. Profound slowing of conduction. Encainide was voluntarily withdrawn from the market, but is still available on a limited basis. 

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. 

Pharmacology Propafenone is a Class 1C antiarrhythmic with local anesthetic effects and direct stabilizing action on myocardial membranes. 

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. 

As propafenone exerts both beta blockade and a (dose-related) negative inotropic effect on cardiac muscle, fully compensate patients with CHF before receiving propafenone. If CHF worsens, discontinue propafenone unless CHF is due to the cardiac arrhythmia and, if indicated, restart at a lower dosage only after adequate cardiac compensation has been established. 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

As with all members of its class, propafenone has its major effect on the fast inward sodium current. The IC agents depress over a wide range of heart rates and shift the resting membrane potential in the direction of hyperpolarization. The 1C agents bind slowly to the sodium channel and dissociate slowly. Therefore, they exhibit rate-dependent block. Inhibition of the sodium channel throughout the cardiac cycle will result in a decrease in the rate of ectopy and trigger ventricular tachycardia. 

Propafenone causes sinus node slowing that could lead to sinoatrial block. It may lengthen the sinus node recovery time with minimal effects on sinus cycle length. 

The action potential duration and ERP of atrial muscle are both prolonged by propafenone. The electrophysiological effects persist beyond removal of the drug from the tissue. In patients with atrial flutter, fibrillation, or tachycardia, propafenone can slow the atrial rate, resulting in a change from 2 1 or 4 1 A-V block to 1 1 A-V conduction with a subsequent increase in the ventricular rate. 

The IV administration of propafenone is accompanied by an increase in right atrial, pulmonary arterial, and pulmonary artery wedge pressures in addition to an increase in vascular resistance and a decrease in the cardiac index. A significant decrease in ejection fraction may be observed in patients with preexisting left ventricular dysfunction. In the absence of cardiac abnormalities, propafenone has no significant effects on cardiac function. 

Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone. 

Lopinavir is available in the United States only as a fixed-dose combination with ritonavir (Kaletra). In this regimen, a low dose of ritonavir is used to inhibit the rapid inactivation of lopinavir by CYP3A4. Side effects, which are generally mild, include diarrhea, nausea, asthenia, and headache. Pancreatitis occurs rarely. Ritonavir is a potent inhibitor of CYP3A4 and also inhibits CYP2D6. In addition to the drugs contraindicated for all protease inhibitors, fiecainide, propafenone, pimozide, and rifampin should not be given with lopinavir-ritonavir combination therapy. 

This agent also has some class lA and class II effects. It is effective for the treatment of ventricular and supraventricular tachycardias (AV nodal and accessory pathway re-entry, atrial flutter and fibrillation). Propafenone is useful in converting recent-onset atrial fibrillation or flutter to sinus rhythm, and for terminating paroxysmal supraventricular tachycardia. Its pro-ariythmic and myocardial depressant effects limit its use, especially in patients with poor ventricular function. 

Propafenone has some structural similarities to propranolol and possesses weak 3-blocking activity. Its spectrum of action is very similar to that of quinidine, but it does not prolong the action potential. Its sodium channel-blocking kinetics are similar to that of flecainide. Propafenone is metabolized in the liver, with an average half-life of 5-7 hours. The usual daily dosage of propafenone is 450-900 mg in three divided doses. The drug is used primarily for supraventricular arrhythmias. The most common adverse effects are a metallic taste and constipation arrhythmia exacerbation can also occur. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

The pharmacokinetics of saquinavir is modified by agents that alter isoenzyme CYP3A4 of the cytochrome P-450 system and P-glycoprotein transporter. It should not be administered with midazolam, triazolam and ergot derivatives. The plasma concentrations of saquinavir are lower when coadministered with efavirenz, nevirapine or rifampin. Ritonavir reverses the effects of nevirapine on saquinavir. The coadministration of astemizole, terfenadine, amiodarone, bepridil, quinidine, propafenone or flecainide with saquinavir is also not recommended due to its potential for serious and/or life-threatening reactions. 

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