This can serve as an important mechanism for suppressing tachycardias that are caused by abnormal conduction e. By decreasing abnormal conduction, re-entry mechanisms can be interrupted. The differences between the three subgroups within class 1 are that, in addition to affecting phase 0 of the action potentials, sodium channel blockers may also alter the action potential duration APD and effective refractory period ERP.
Because some sodium channel blockers increase the ERP class 1-A , while others decrease it class 1-B or have no effect on it class 1-C , the Vaughan—Williams classification recognizes these differences as subclasses of class 1 antiarrhythmic drugs.
The effects on ERP are not directly related to the 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 class 1-C drugs having the greatest and class 1-B drugs having the smallest effect on phase 0 class 1-A drugs are intermediate in their effect on phase 0. Increasing or decreasing the APD and ERP can either increase or decrease arrhythmogenesis, depending on the underlying cause of the arrhythmia.
Increasing the ERP, for example, can interrupt tachycardia caused by re-entry mechanisms class 1-A by prolonging the duration that normal tissue is unexcitable its refractory period.
This can prevent re-entry currents from reexciting the tissue, as happens with Wolff—Parkinson—White syndrome WPW , which is caused by an aberrant pathway. On the other hand, increasing the APD can precipitate torsades de pointes, a type of ventricular tachycardia caused by afterdepolarizations abnormal depolarizations of cardiac myocytes that interrupt phase 2, phase 3, or phase 4 of the cardiac action potential in the electrical conduction system of the heart.
Class 1 antiarrhythmic agents can suppress abnormal automaticity by decreasing the slope of phase 4, which is generated by pacemaker currents. The mechanism for this is not understood and is unrelated to blocking fast sodium channels. The anticholinergic effect seen with this group of drugs increases the conduction along the SA and AV pathways.
Thus, in a patient with atrial flutter , although the ventricular rate will be reduced by their sodium blocking property, class 1 antiarrhythmics can lead to an increase in both the SA rate and the AV conduction, which can offset the direct effects of the drugs on these tissues. Although a class 1-A drug may effectively decrease the atrial rate during flutter, it can lead to an increase in ventricular rate because of an increase in the number of impulses conducted through the AV node anticholinergic effect , thereby requiring concomitant treatment with a beta blocker or calcium channel blocker to slow the AV nodal conduction.
These anticholinergic actions are most prominent at the SA and AV nodes because they are extensively innervated by vagal afferent nerves. Different drugs within the class 1-A subclassification differ in their anticholinergic actions. Image : Atrial flutter with variable block between 3 and 4 to 1. By James Heilman, MD.
All three classes of drugs are indicated for the treatment of ventricular tachyarrhythmias. In addition, class 1-C drugs are very valuable in the life-threatening supraventricular tachyarrhythmias flecainide and propafenone. Class 1-A drugs also have an effect on atrial fibrillation , along with flutter and supraventricular tachycardia. The side effects are discussed in detail for individual drugs. The increase or decrease in action potential duration and the effective refractory period can act as a double-edged sword.
Both of these mechanisms prevent the re-entry circuits, but, at the same time, they increase the potential for causing torsades de pointes. The proarrhythmogenic potential is generally seen in this group of drugs. In addition to the indications discussed above, important consideration needs to be given to those patients who have uncontrolled atrial fibrillation.
The administration of disopyramide will cause an increase in the AV nodal conduction, thereby increasing the ventricular rate in these patients. This effect also occurs with procainamide and quinidine. Treatment with beta blockers, digoxin, or a calcium channel blocker is required. Disopyramide is deemed safe in patients with hypertrophic cardiomyopathy and is shown to have beneficial effects. Disopyramide has significant cardiac toxicity: It decreases the contraction of the heart negative inotropic effect and has the potential to cause arrhythmia.
A common side effect of disopyramide is related to its anticholinergic effects. This includes dryness of the mouth, hesitancy during urination, and constipation. In conditions in which cholinergic activity is already decreased such as in myasthenia gravis, in which antibodies against acetylcholine receptors are formed , the administration of this drug will aggravate the condition. License: CC BY 3. The other conditions in which caution needs to be exercised are acute angle closure glaucoma and urinary retention.
Although it is rare, hypoglycemia may occur with disopyramide therapy because disopyramide may induce inhibition of the K—ATP channels. Roden, Dan M. Borchard, U. Noble, D. Bigger, J. Thomas, and William J. Cheng, Tsung O. Class I antiarrhythmic agents. Previous chapter: Classification of antiarrhythmic agents Next chapter: Amiodarone. All SAQs related to this topic. All vivas related to this topic. In summary: Common features of all Class I agents: All have local anaesthetic effects All bind to a site in the pore of the Nav1.
Class Ia antiarrhythmic. Class Ib antiarrhythmic. Class Ic antiarrhythmic. Routes of administration. Oral and IV. IV, inhaled, subcutaneous. Highly water soluble; pKa 9. Target receptor. Hepatic metabolism of some variable fraction, into active metabolites NAPA. Half-life hours; a significant proportion of the drug is excreted unchanged in the urine. Minimally renally excreted; half-life minutes following IV bolus. Time course of action. Duration of action is similar to half-life.
Single best reference for further information. Giardina Weinberg et al 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:.
Increasing or decreasing the APD and ERP can either increase or decrease arrhythmogenesis, depending on the underlying cause of the arrhythmia. Increasing the ERP, for example, can interrupt tachycardia caused by reentry mechanisms by prolonging the duration that normal tissue is unexcitable its refractory period. This can prevent reentry currents from re-exciting the tissue.
On the other hand, increasing the APD can precipitate torsades de pointes , a type of ventricular tachycardia caused by afterdepolarizations. Several classes of antiarrhythmics, including beta blockers , calcium channel blockers , amiodarone , cardiac glycosides , and lidocaine , also have other medical uses, which are discussed in their respective articles.
Class IA antiarrhythmics. All antiarrhythmic drugs are also potentially proarrhythmic! Intravenous administration should only be performed with continuous cardiac monitoring! Di ltiazem and Ve rapamil Di minish conduction Ve locity.
Class I B antiarrhythmic drugs work B est after myocardial infarction ; class I C antiarrhythmic drugs are C ontraindicated. References: [6] [7] [8]. Avoid adenosine in patients with suspected pre-excitation tachycardia e. IV abradine slows depolarization in phase IV. Expand all sections Register Log in.
Trusted medical expertise in seconds. Find answers fast with the high-powered search feature and clinical tools. Try free for 5 days Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer. Antiarrhythmic drugs. Summary Antiarrhythmic drugs are used to prevent recurrent arrhythmias and restore sinus rhythm in patients with cardiac arrhythmias.
Overview Classes of antiarrhythmic drugs [1] [2] Class Drug group Mechanism of action Examples Use Adverse effects Class IA antiarrhythmics Fast sodium channel blockers Reduce or even block conduction negative dromotropy , particularly in depolarized tissue e.
Modern Pharmacology with Clinical Applications.
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