항부정맥제

심장 활동전위에 영향을 미치는 약물들. 전압이 급격히 올라가는 시기("0")는 나트륨 이온의 유입 때문이다. 반면 전압이 떨어지는 두 시기("1", "3")는 나트륨 통로가 비활성화되고 칼륨 이온이 밖으로 나가면서 재분극이 일어나는 시기이다. 특징적인 고원기("2")는 전압 의존성 칼슘 통로가 열려 발생한다.

항부정맥제(antiarrhythmic agents, cardiac dysrhythmia medications)는 심장의 비정상적인 리듬인 부정맥을 억제하기 위해 사용하는 약물들의 그룹이다. 부정맥의 예로는 심방세동, 심방조동, 심실빈맥, 심실세동이 있다.

항부정맥제를 분류하기 위한 많은 시도가 있어왔다. 문제는 많은 항부정맥제가 여러 작용을 가져 분류 방식을 부정확하게 만든다는 것이다.

본 윌리엄스 분류

본 윌리엄스 분류는 1970년 마일스 본 윌리엄스(Miles Vaughan Williams)에 의해 도입되었다.

본 윌리엄스는 옥스포드 하트퍼드 칼리지의 약리학 강사였다. 그의 학생 중 한 명이었던 브라마 N. 싱(Bramah N. Singh)이 분류 체계 발전에 기여했다. 따라서 이 분류 체계는 간혹 싱-본 윌리엄스 분류로도 불린다

항부정맥제의 본 윌리엄스 분류에서 다섯 개의 주된 클래스는 다음과 같다.

• 클래스 I 약제는 나트륨 통로에 작용한다.
• 클래스 II 약제는 교감신경계를 길항하는 약제이다. 이 클래스에 속하는 대부분의 약제는 베타 차단제이다.
• 클래스 III 약제는 칼륨 이온(K⁺)의 유출에 관여한다.
• 클래스 IV 약제는 칼슘 통로와 방실결절에 영향을 미친다.
• 클래스 V 약제는 기타 다른 기전에 의해 작용하거나 기전이 알려져 있지 않은 약제이다.

심방세동을 관리할 때 클래스 I과 III의 약제는 심장 리듬의 조절에 사용되며, 클래스 II와 IV의 약제는 속도를 조절하는 약제로 사용된다.

클래스	종류	예시	작용 기전	의학적 사용 목적
Ia	빠른 이온 통로 차단제	퀴니딘 Ajmaline Procainamide Disopyramide Sparteine	Na+ channel block (intermediate association/dissociation) and K+ channel blocking effect. Class 1a prolong the action potential and has intermediate effect on the 0 phase of depolarization	Treat ventricular arrhythmia Prevent paroxysmal recurrent atrial fibrillation triggered by vagal overactivity Treat Wolff-Parkinson-White syndrome (procainamide) Increase QT interval
Ib		리도카인 페니토인 Mexiletine Tocainide	Na+ channel block (fast association/dissociation). Class 1b shorten the action potential of myocardial cell and has weak effect on initiation of phase 0 of depolarization	Treat and prevent ventricular arrhythmia during and immediately after myocardial infarction, though this is now discouraged given the increased risk of asystole
Ic		Encainide Flecainide Propafenone Moricizine	Na+ channel block (slow association/dissociation). Class 1c do not affect action potential duration and have the strongest effect on the initiation phase 0 of depolarization	Prevent paroxysmal atrial fibrillation Treat recurrent tachycardia associated with abnormal conduction pathways, such as Wolff–Parkinson–White syndrome Contraindicated immediately after myocardial infarction
II	베타 차단제	카르베딜롤 프로프라놀롤 에스몰롤 티몰롤 메토프롤롤 아테놀롤 비소프롤롤 네비볼롤	베타 차단제 프로프라놀롤은 약간의 나트륨 통로 차단 효과도 가진다.	심근 경색 환자의 사망률을 감소시킴 빈맥 재발을 예방함
III	Potassium channel blockers	Amiodarone 소탈롤 Ibutilide Dofetilide Dronedarone E-4031 Vernakalant	K+ channel blocker Sotalol is also a beta blocker Amiodarone has Class III mostly, but also I, II, & IV activity	Treat Wolff-Parkinson-White syndrome 심실빈맥과 심방세동 치료(소탈롤) 심방조동과 심방세동 치료(ibutilide) Prevent paroxysmal atrial fibrillation and haemodynamically stable ventricular tachycardia (amiodarone)
IV	Calcium channel blockers	베라파밀 Diltiazem	칼슘 통로 차단제	Prevent recurrence of paroxysmal supraventricular tachycardia Reduce ventricular rate in patients with atrial fibrillation
V		아데노신 디곡신 Magnesium sulfate	Work by other or unknown mechanisms (direct nodal inhibition)	Treat supraventricular arrhythmias, especially in heart failure with atrial fibrillation Contraindicated in ventricular arrhythmias Treat torsades de pointes (magnesium sulfate)

Class I agents

The class I antiarrhythmic agents interfere with the sodium channel. Class I agents are grouped by what effect they have on the Na⁺ channel, and what effect they have on cardiac action potentials.

Class I agents are called membrane-stabilizing agents, "stabilizing" referring to the decrease of excitogenicity of the plasma membrane which is brought about by these agents. (Also noteworthy is that a few class II agents like propranolol also have a membrane stabilizing effect.)

Class I agents are divided into three groups (Ia, Ib, and Ic) based upon their effect on the length of the action potential.

• Ia lengthens the action potential (right shift)
• Ib shortens the action potential (left shift)
• Ic does not significantly affect the action potential (no shift)

• 

  Class Ia

• 

  Class Ib

• 

  Class Ic

Class II agents

Class II agents are conventional beta blockers. They act by blocking the effects of catecholamines at the β₁-adrenergic receptors, thereby decreasing sympathetic activity on the heart, which reduces intracellular cAMP levels and hence reduces Ca²⁺ influx. These agents are particularly useful in the treatment of supraventricular tachycardias. They decrease conduction through the AV node.

Class II agents include atenolol, esmolol, propranolol, and metoprolol.

Class III agents

Class III

Class III agents predominantly block the potassium channels, thereby prolonging repolarization. Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is less likely to interact with tissue that has become refractory). The class III agents exhibit reverse-use dependence (their potency increases with slower heart rates, and therefore improves maintenance of sinus rhythm). Inhibiting potassium channels, slowing repolarization, results in slowed atrial-ventricular myocyte repolarization. Class III agents have the potential to prolong the QT interval of the EKG, and may be proarrhythmic (more associated with development of polymorphic VT).

Class III agents include: bretylium, amiodarone, ibutilide, sotalol, dofetilide, vernakalant, and dronedarone.

Class IV agents

Class IV agents are slow non-dihydropyridine calcium channel blockers. They decrease conduction through the AV node, and shorten phase two (the plateau) of the cardiac action potential. They thus reduce the contractility of the heart, so may be inappropriate in heart failure. However, in contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility.

Class IV agents include verapamil and diltiazem.

Class V and others

Since the development of the original Vaughan Williams classification system, additional agents have been used that do not fit cleanly into categories I through IV. Such agents include:

• Digoxin, which decreases conduction of electrical impulses through the AV node and increases vagal activity via its central action on the central nervous system, via indirect action, leads to an increase in acetylcholine production, stimulating M2 receptors on AV node leading to an overall decrease in speed of conduction.
• Adenosine is used intravenously for terminating supraventricular tachycardias.
• Magnesium sulfate, an antiarrhythmic drug, but only against very specific arrhythmias which has been used for torsades de pointes.
• Trimagnesium dicitrate (anhydrous) as powder or powder caps in pure condition, better bioavailability than ordinary MgO

History

The initial classification system had 4 classes, although their definitions different from the modern classification. Those proposed in 1970 were:

1. Drugs with a direct membrane action: the prototype was quinidine, and lignocaine was a key example. Differing from other authors, Vaughan-Williams describe the main action as a slowing of the rising phase of the action potential.
2. Sympatholytic drugs (drugs blocking the effects of the sympathetic nervous system): examples included bretylium and adrenergic beta-receptors blocking drugs. This is similar to the modern classification, which focuses on the latter category.
3. Compounds that prolong the action potential: matching the modern classification, with the key drug example being amiodarone, and a surgical example being thyroidectomy. This was not a defining characteristic in an earlier review by Charlier et al. (1968), but was supported by experimental data presented by Vaughan Williams (1970). The figure illustrating these findings was also published in the same year by Singh and Vaughan Williams.
4. Drugs acting like dephenylhydantoin (DPH): mechanism of action unknown, but others had attributed its cardiac action to an indirect action on the brain; this drug is better known as antiepileptic drug phenytoin.

Sicilian gambit classification

Another approach, known as the "Sicilian gambit", placed a greater approach on the underlying mechanism.

It presents the drugs on two axes, instead of one, and is presented in tabular form. On the Y axis, each drug is listed, in roughly the Singh-Vaughan Williams order. On the X axis, the channels, receptors, pumps, and clinical effects are listed for each drug, with the results listed in a grid. It is, therefore, not a true classification in that it does not aggregate drugs into categories.

A modernized Oxford classification by Lei, Huang, Wu, and Terrar

Common anti-arrhythmic drugs under the modernized classification according to Lei et al. 2018

A recent publication (2018) has now emerged with a fully modernised drug classification. This preserves the simplicity of the original Vaughan Williams framework while capturing subsequent discoveries of sarcolemmal, sarcoplasmic reticular and cytosolic biomolecules. The result is an expanded but pragmatic classification that encompasses approved and potential anti-arrhythmic drugs. This will aid our understanding and clinical management of cardiac arrhythmias and facilitate future therapeutic developments. It starts by considering the range of pharmacological targets, and tracks these to their particular cellular electrophysiological effects. It retains but expands the original Vaughan Williams classes I to IV, respectively covering actions on Na+ current components, autonomic signalling, K⁺ channel subspecies, and molecular targets related to Ca²⁺ homeostasis. It now introduces new classes incorporating additional targets, including:

• Class 0: ion channels involved in automaticity
• Class V: mechanically sensitive ion channels
• Class VI: connexins controlling electrotonic cell coupling
• Class VII: molecules underlying longer term signalling processes affecting structural remodeling.

It also allows for multiple drug targets/actions and adverse pro-arrhythmic effects. The new scheme will additionally aid development of novel drugs under development and is illustrated here.

같이 보기

• Cardiac Arrhythmia Suppression Trial (CAST)
• 심전도
• 항부정맥제(분류)
• Proarrhythmic agent

참고 문헌

틀:주요약물군

This article "항부정맥제" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:항부정맥제. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.

This page exists already on Wikipedia.

---

 Facebook Page

🐤 Twitter Follow us on Twitter !

Read or create/edit this page in another language

• 항부정맥제 in English