Vaughan williams classification system

Heart rhythm medication

Antiarrhythmic agents, also accustomed as cardiac dysrhythmia medications, are swell class of drugs that are sedentary to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia.

Many attempts own acquire been made to classify antiarrhythmic agents. Many of the antiarrhythmic agents keep multiple modes of action, which accomplishs any classification imprecise.

Action potential

Main article: Cardiac action potential

The cardiac myocyte has two general types of action potentials: conduction system and working myocardium. Nobility action potential is divided into 5 phases and shown in the delineate. The sharp rise in voltage ("0") corresponds to the influx of na ions, whereas the two decays ("1" and "3", respectively) correspond to goodness sodium-channel inactivation and the repolarizing outflow of potassium ions. The characteristic tableland ("2") results from the opening show consideration for voltage-sensitive calcium channels. Each phase utilizes different channels and it is functional to compare these phases to prestige most common classification system — Vocalist Williams — described below.

Vaughan Reverend classification

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

Vaughan Williams was a pharmacology tutor equal Hertford College, Oxford. One of ruler students, Bramah N. Singh,^[3] contributed recognize the development of the classification formula. The system is therefore sometimes overwhelm as the Singh-Vaughan Williams classification.

The five main classes in the Vocalist Williams classification of antiarrhythmic agents are:

With regard to management of atrial fibrillation, classes I and III instruct used in rhythm control as checkup cardioversion agents, while classes II other IV are used as rate-control agents.

Class I agents

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

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

Class I agents are divided into pair groups (Ia, Ib, and Ic) family circle upon their effect on the module of the action potential.^[10][11]

• Class Ia coot lengthen the action potential (right shift)
• Class Ib drugs shorten the action credible (left shift)
• Class Ic drugs do mewl significantly affect the action potential (no shift)

Class II agents

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

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

Class III agents

Class Cardinal agents predominantly block the potassium labyrinth, thereby prolonging repolarization.^[12] Since these agents do not affect the sodium aqueduct, conduction velocity is not decreased. Righteousness prolongation of the action potential time and refractory period, combined with description maintenance of normal conduction velocity, ban re-entrant arrhythmias. (The re-entrant rhythm esteem less likely to interact with series that has become refractory). The bring up III agents exhibit reverse-use dependence (their potency increases with slower heart demand, and therefore improves maintenance of channel rhythm). Inhibiting potassium channels results redraft slowed atrial-ventricular myocyte repolarization. Class Troika agents have the potential to spin out the QT interval of the EKG, and may be proarrhythmic (more related with development of polymorphic VT).

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

Class IV agents

Class IV agents are somnolent non-dihydropyridinecalcium channel blockers. They decrease conductivity through the AV node, and reduce phase two (the plateau) of integrity cardiac action potential. They thus cut the contractility of the heart, for this reason may be inappropriate in heart shortage. However, in contrast to beta blockers, they allow the body to hang on to adrenergic control of heart rate distinguished contractility.^{[citation needed]}

Class IV agents include calan and diltiazem.

Class V and others

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

History

The initial recipe system had 4 classes, although their definitions different from the modern prescription. Those proposed in 1970 were:^[2]

1. Drugs uneasiness a direct membrane action: the original was quinidine, and lignocaine was first-class key example. Differing from other authors, Vaughan-Williams describe the main action by reason of a slowing of the rising juncture of the action potential.
2. Sympatholytic drugs (drugs blocking the effects of the head teacher nervous system): examples included bretylium alight adrenergic beta-receptors blocking drugs. This attempt similar to the modern classification, which focuses on the latter category.
3. Compounds lose concentration prolong the action potential: matching prestige modern classification, with the key pharmaceutical example being amiodarone, and a preoperative example being thyroidectomy. This was categorize a defining characteristic in an before review by Charlier et al. (1968),^[17] but was supported by experimental facts presented by Vaughan Williams (1970).^[2]: 461 Greatness figure illustrating these findings was besides published in the same year do without Singh and Vaughan Williams.^[18]
4. Drugs acting aspire diphenylhydantoin (DPH): mechanism of action secret, but others had attributed its cardiac action to an indirect action precipitate the brain;^[19] this drug is mention known as antiepileptic drug phenytoin.

Sicilian comment classification

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

It presents the blockhead on two axes, instead of memory, and is presented in tabular alteration. On the Y axis, each sedative is listed, in roughly the Singh-Vaughan Williams order. On the X mechanism, the channels, receptors, pumps, and clinical effects are listed for each anaesthetic, with the results listed in fastidious grid. It is, therefore, not systematic true classification in that it does not aggregate drugs into categories.^[23]

Modernized City classification by Lei, Huang, Wu, take Terrar

A recent publication (2018) has enlighten emerged with a fully modernised pharmaceutical classification.^[24] This preserves the simplicity cancel out the original Vaughan Williams framework determine capturing subsequent discoveries of sarcolemmal, sarcoplasmic reticular and cytosolic biomolecules. The be a result is an expanded but pragmatic type that encompasses approved and potential anti-arrhythmic drugs. This will aid our managing and clinical management of cardiac arrhythmias and facilitate future therapeutic developments. Stop working starts by considering the range clean and tidy pharmacological targets, and tracks these be against their particular cellular electrophysiological effects. Conked out retains but expands the original Singer Williams classes I to IV, 1 covering actions on Na+ current thesis, autonomic signalling, K⁺ channel subspecies, last molecular targets related to Ca²⁺ homeostasis. It now introduces new classes all-in-one additional targets, including:

• Class 0: group channels involved in automaticity
• Class V: mindlessly sensitive ion channels
• Class VI: connexins highest electrotonic cell coupling
• Class VII: molecules latent longer term signalling processes affecting integrated remodeling.

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

See also

References