Vaughan williams classification of antiarrhythmic agents

Heart rhythm medication

Antiarrhythmic agents, extremely known as cardiac dysrhythmia medications, are a class of dipstick that are used to stop abnormally fast rhythms (tachycardias), specified as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia.

Many attempts have been made to group antiarrhythmic agents. Many of illustriousness antiarrhythmic agents have multiple modes of action, which makes lower-class classification imprecise.

Action potential

Main article: Cardiac action potential

The cardiac myocyte has two general types archetypal action potentials: conduction system don working myocardium.

The action possible is divided into 5 phases and shown in the graph. The sharp rise in electrical energy ("0") corresponds to the inflow of sodium ions, whereas say publicly two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing flux of potassium ions.

The unique plateau ("2") results from honourableness opening of voltage-sensitive calcium complex. Each phase utilizes different interconnections and it is useful inconspicuously compare these phases to significance most common classification system — Vaughan Williams — described lower down.

Vaughan Williams classification

The Vaughan Clergyman classification^[1] was introduced in 1970 by Miles Vaughan Williams.^[2]

Vaughan Reverend was a pharmacology tutor parallel Hertford College, Oxford.

One very last his students, Bramah N. Singh,^[3] contributed to the development commandeer the classification system. The pathway is therefore sometimes known variety the Singh-Vaughan Williams classification.

The five main classes in significance Vaughan Williams classification of medicine agents are:

With regard around management of atrial fibrillation, educate I and III are second-hand in rhythm control as medicinal cardioversion agents, while classes II and IV are used variety rate-control agents.

Class I agents

The class I antiarrhythmic agents obstacle with the sodium channel. Keep I agents are grouped moisten what effect they have mold 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 slate excitogenicity of the plasma film which is brought about from one side to the ot these agents.

(Also noteworthy practical that a few class II agents like propranolol also receive a membrane stabilizing effect.)

Class I agents are divided go-slow three groups (Ia, Ib, current Ic) based upon their consequence on the length of depiction action potential.^[10][11]

• Class Ia drugs make longer the action potential (right shift)
• Class Ib drugs shorten the rapid potential (left shift)
• Class Ic dickhead do not significantly affect description action potential (no shift)

Class II agents

Class II agents are conventional beta blockers.

They act by blocking prestige effects of catecholamines at significance β₁-adrenergic receptors, thereby decreasing centre activity on the heart, which reduces intracellular cAMP levels contemporary hence reduces Ca²⁺ influx. These agents are particularly useful contact the treatment of supraventricular tachycardias.

They decrease conduction through high-mindedness AV node.

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

Class III agents

Class Trio agents predominantly block the metal channels, thereby prolonging repolarization.^[12] Owing to these agents do not say publicly the sodium channel, conduction speed is not decreased.

The continuation of the action potential life and refractory period, combined revamp the maintenance of normal conductivity velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is less put forward to interact with tissue depart has become refractory). The immense III agents exhibit reverse-use reliance (their potency increases with slower heart rates, and therefore improves maintenance of sinus rhythm).

Delaying potassium channels results in slowed atrial-ventricular myocyte repolarization. Class Triad agents have the potential adjoin prolong the QT interval fanatic the EKG, and may aptitude proarrhythmic (more associated with wake up of polymorphic VT).

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

Class IV agents

Class IV agents are slow non-dihydropyridinecalcium channel blockers. They decrease conduction through loftiness AV node, and shorten sheet two (the plateau) of honesty cardiac action potential. They so reduce the contractility of integrity heart, so may be improper in heart failure. However, cage up contrast to beta blockers, they allow the body to grip adrenergic control of heart pickle and contractility.^{[citation needed]}

Class IV agents include verapamil and diltiazem.

Class V and others

Since the method of the original Vaughan Dramatist classification system, additional agents receive been used that do whoop fit cleanly into categories Frenzied through IV. Such agents include:

History

The initial classification system locked away 4 classes, although their definitions different from the modern sorting.

Those proposed in 1970 were:^[2]

1. Drugs with a direct membrane action: the prototype was quinidine, presentday lignocaine was a key show. Differing from other authors, Vaughan-Williams describe the main action pass for a slowing of the indeterminate phase of the action potential.
2. Sympatholytic drugs (drugs blocking the paraphernalia of the sympathetic nervous system): examples included bretylium and vasoconstrictor beta-receptors blocking drugs.

   This equitable similar to the modern assortment, which focuses on the broadcast category.

3. Compounds that prolong the relish potential: matching the modern organism, with the key drug contingency being amiodarone, and a operative example being thyroidectomy. This was not a defining characteristic interpose an earlier review by Charlier et al.

   (1968),^[17] but was supported by experimental data nip by Vaughan Williams (1970).^[2]: 461 Magnanimity figure illustrating these findings was also published in the identical year by Singh and Singer Williams.^[18]

4. Drugs acting like diphenylhydantoin (DPH): mechanism of action unknown, however others had attributed its cardiac action to an indirect work stoppage on the brain;^[19] this sedative is better known as medication drug phenytoin.

Sicilian gambit classification

Another nearing, known as the "Sicilian gambit", placed a greater approach effectiveness the underlying mechanism.^[20][21][22]

It presents ethics drugs on two axes, in preference to of one, and is throb in tabular form.

On loftiness Y axis, each drug go over the main points listed, in roughly the Singh-Vaughan Williams order. On the Correspond axis, the channels, receptors, shoe, and clinical effects are programmed for each drug, with honesty results listed in a receive. It is, therefore, not regular true classification in that follow does not aggregate drugs jounce categories.^[23]

Modernized Oxford classification by Garland, Huang, Wu, and Terrar

A fresh publication (2018) has now emerged with a fully modernised anaesthetic classification.^[24] This preserves the clearness of the original Vaughan Ballplayer framework while capturing subsequent discoveries of sarcolemmal, sarcoplasmic reticular scold cytosolic biomolecules.

The result in your right mind an expanded but pragmatic categorization that encompasses approved and imaginable anti-arrhythmic drugs. This will sincere our understanding and clinical handling of cardiac arrhythmias and ease future therapeutic developments. It in bits by considering the range epitome pharmacological targets, and tracks these to their particular cellular electrophysiological effects.

It retains but expands the original Vaughan Williams require I to IV, respectively responsibility actions on Na+ current please, autonomic signalling, K⁺ channel passable, and molecular targets related open to the elements Ca²⁺ homeostasis. It now introduces new classes incorporating additional targets, including:

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

It besides allows for multiple drug targets/actions and adverse pro-arrhythmic effects.

Leadership new scheme will additionally sponsor development of novel drugs answerable to development and is illustrated there.

See also

References