What is the significance of the action potential as it relates to antidysrhythmics

Nelson L. Nelson, Lewis S. Hoffman R. Robert S. Hoffman, et al. Goldfrank's Toxicologic Emergencies, 10e. McGraw Hill; Accessed November 14, McGraw Hill. Download citation file: RIS Zotero. Reference Manager. Autosuggest Results. Subscribe: Institutional or Individual. Username Error: Please enter User Name.

Class Ia drugs produce anticholinergic effects on the heart due to their ability to block m2 receptors quinidine or block autonomic ganglia procainamide. Anticholinergic side effects include urinary retention in male patients with prostate hypertrophy, dry mouth , blurred vision , constipation and worsening of pre-existing glaucoma. An additional, potentially life-threatening situation of dangerous acceleration of ventricular rate can also occur when attempting to treat atrial flutter or fibrillation with a Class Ia drug alone see Figure Why does this occur?

Why is this potentially harmful? What would you do differently to prevent it from occurring? Effect of quinidine on atrial and ventricular rate when used alone to treat atrial flutter. A dog was placed under alpha-chloralose anesthesia and atrial flutter was induced by programmed electrical stimulation of the atrium at a frequency of 20 Hz after first crushing the atrial muscle between the superior and inferior vena cavae.

Repeated attempts to re-initiate flutter S were unsuccessful. The experimental preparation closely duplicates the response in clinical cases. This side effect is especially important when treating patients with systolic heart failure low ejection fraction. Drugs with a clinically significant negative inotropic effect in decreasing order of severity include:. These include:. Torsade can be produced by more than 40 drugs that block IKr the rapid component of repolarization current in ventricular myocytes.

This is one reason why patients being initialized on most Class Ia or Class III drugs are hospitalized for the first day or two when initializing treatment when this event is most likely to occur. Amiodarone is an exception — it has a very low incidence of producing Torsade, perhaps because it behaves like a pharmacological shotgun - it blocks multiple currents, including those that contribute to the depolarizing upstroke of action potentials that produce EADs.

Torsade is potentially life-threatening and is treated as a medical emergency. Several lines of evidence implicate that either Early After Depolarizations EADs or enhanced transmural dispersion of repolarization can result in the triggered activity that is the genesis of Torsade de pointes:.

Two proposed mechanisms for formation of Torsade. Panel A: Isolated Purkinje fiber preparation. EADs develop when the balance of currents active during phase 2 or 3 shifts in the inward vs. Cells from the mid-wall region have a longer APD compared to endocardial or epicardial cells, and greater sensitivity to the effects of APD-prolonging drugs. Under the combination of such drugs and slowing of the heart rate, the M cell APD widens disproportionately, resulting in an abnormally large dispersion of APD values between regions as indicated by the width between the two vertical lines.

The source for depolarization can be either the L-type Ca current, Na-Ca exchange current, or a late plateau Na current indicated by the red arrow Figure modified after Roden, Atrial fibrillation AFib is the most common cardiac arrhythmia , currently affecting more than 2 million Americans. It is rarely a one-time event. Current research indicates that this is primarily due to a change in the expression of ion channels that is caused by fibrillation which may be mediated by changes in intracellular calcium caused by rapid pacing.

Some of the characteristics associated with AFib are:. Arguments in favor of rhythm control include: 1 rhythm control reduces the odds of thromboembolism; 2 it was thought that patients who remain in AFib have a worse outcome than those treated with drugs that maintain a sinus rhythm.

Of course! Who would argue with that? In both studies, rhythm control provided no advantage over ventricular rate control with respect to survival Fig 15A. Surgical procedures e.

Mini Maze procedure involving catheter ablation of ectopic foci around the pulmonary veins may also be successful in patients with otherwise relatively normal hearts. From Roy et al, Panel B: Kaplan-Meier Estimates of the Percentage of Patients Remaining Free of Recurrence of Atrial Fibrillation in the two treatment groups hazard ratio for recurrence among patients in the amiodarone group, 0.

Follow-up began 21 days after randomization designated day 0. From: Roy et al, Currently amiodarone appears to be superior to other antiarrhythmics in preventing the reoccurrence of AFib Figure 15B.

Patients who are placed on rate control treatment are typically given maintenance therapy with either verapamil, diltiazem, a beta blocker or digoxin digoxin use is more common if the patient has systolic HF. If emergency cardioversion is considered, a transesophageal echocardiogram can be used to determine the presence or absence of left atrial thrombi.

Show pagesource. Old revisions. Recent Changes. Explain which antiarrhythmic drug class is contraindicated in the chronic treatment of patients with a history of myocardial ischemia.

Describe which drug class reduces the incidence of sudden death and reinfarction after an MI. List the primary drugs used for acute and chronic treatment of AV node reentry. Cite major drug-specific side effects that limit the clinical use of antiarrhythmics. Explain the multiple mechanisms by which amiodarone may exert its antiarrhythmic effects against atrial and ventricular arrhythmias.

Class I : lidocaine , procainamide , propafenone quinidine: rarely used. Class II : propranolol , metoprolol. Class IV : verapamil, diltiazem.

Misc : adenosine. What are the risk factors associated with chronic atrial fibrillation? What are the two primary treatment options for patients with atrial fibrillation? How does diltiazem exert a beneficial effect in the treatment of atrial fibrillation? Is there a pharmacological vs. Why was four weeks of anticoagulation necessary prior to conversion of the patient's atrial fibrillation back to sinus rhythm? Why is amiodarone used in treating atrial fibrillation?

Arrhythmias that typically require treatment fall into 3 basic categories: arrhythmias that decrease cardiac output e. While detailed discussion of these treatments is beyond the scope of this course, they include: DC cardioversion wikipedia , implanting of a pacemaker, or defibrillator device ICD. Surgical or catheter-mediated ablation of an ectopic focus, coronary bypass surgery.

Lifestyle modification avoiding events that aggravate an arrhythmia - e. Class I drugs: block cardiac Na channels but Ia drugs also block K channels. There are at least 3 ways that Class I drugs can produce this effect: Many Class I drugs block the I h I f pacemaker current expressed in Purkinje fibers. Hence ectopic pacemakers that utilize I h for spontaneous diastolic depolarization Figure 2 will be suppressed in the presence of such drugs.

This effect can be relatively selective for ectopic pacemakers because multiple currents including the L-type Ca current are responsible for regulating the automaticity in the SA node.

Partial block of Na channels can shift the threshold for producing an action potential to shift to more positive voltage levels , which prolongs the period of diastolic depolarization in-between spontaneous beats. Class Ia drugs increase the action potential duration by blocking IKr, which can also contribute modestly to slowing of the spontaneous firing rate of ectopic foci.

Arrhythmias induced by DAD's e. Increase in ERP in depolarized ischemic tissue. A critical number of channels must exist in an unblocked rested state to allow conduction of an action potential to occur. Since drug unbinding is not instantaneous, some channels will be blocked at the end of the action potential, especially in cells with a depolarized resting potential see Figure 4. If the ERP is increased beyond the conduction time around a reentrant circuit, reentry can no longer occur. Dependence of drug effect on heart rate.

As the heart rate is increased the diastolic interval will shorten, resulting in progressively incomplete drug unbinding, and a rate-dependent increase in drug effect to slow conduction.

Selective depression of conduction in depolarized tissue. If the resting membrane potential becomes depolarized, some channels will exist in a high-affinity inactivated state at all times.

This can abolish reentry by converting a depolarized partially ischemic zone from a region of unidirectional block to a region of bidirectional block by making it totally inexcitable. The principal effect of reducing the rate and magnitude of depolarization by blocking sodium channels is a decrease in conduction velocity in non-nodal tissue atrial and ventricular muscle, purkinje conducting system.

The faster a cell depolarizes, the more rapidly adjacent cells will become depolarized, leading to a more rapid regeneration and transmission of action potentials between cells. Therefore, blocking sodium channels reduces the velocity of action potential transmission within the heart reduced conduction velocity; negative dromotropy.

This can serve as an important mechanism for suppressing tachycardias that are caused by abnormal conduction e. By depressing abnormal conduction, reentry mechanisms can be interrupted. Besides affecting phase 0 of action potentials, sodium-channel blockers may also alter the action potential duration APD and effective refractory period ERP. These effects on ERP are not directly related to sodium channel blockade, but instead are related to drug actions on potassium channels involved in phase 3 repolarization of action potentials.

The drugs in these subclasses also differ in their efficacy for reducing the slope of phase 0, with IC drugs having the greatest and IB drugs having the smallest effect on phase 0 IA drugs are intermediate in their effect on phase 0.

The following summarize these differences:. Last updated: September 4, Flecainide: Drug information. Last updated: January 1, Accessed: October 10, Quinidine: Drug information. Le T, Bhushan V. McGraw-Hill Education ; Fast sodium channel blockers. Reduce or even block conduction negative dromotropy , particularly in depolarized tissue e. Quinidine Procainamide Disopyramide Ajmaline. Lidocaine Mexiletine Phenytoin. Ventricular arrhythmias especially following myocardial infarction Digitalis -induced cardiac arrhythmias.

Flecainide Propafenone. Proarrhythmogenic: c ontraindicated following myocardial infarction Possible QT prolongation due to increased QRS duration [3]. Beta blockers. AV block , bradycardia , heart failure Exacerbation of asthma , COPD Sedation, CNS depression , sleep alterations Impotence Hypoglycemia can mask symptoms of hypoglycemia Hyperkalemia Dyslipidemia metoprolol Propanolol: may intensify vasospams in patients with preexisting vasospastic angina Avoid in patients with concurrent cocaine use or pheochromocytoma.

Potassium channel blockers. AFib cardioversion and rhythm control Atrial flutter Sotalol and amiodarone can be used to treat: Supraventricular arrhythmias Ventricular arrhythmias , e.