Potassium channel blocker
Encyclopedia
Potassium channel blockers are agents which interfere with conduction through potassium channel
s.
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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).
Class III antiarrhythmic agents exhibit reverse use dependent prolongation of the action potential duration (Reverse use-dependence). This means that the refractoriness of the ventricular myocyte
increases at lower heart rate
s. This increases the susceptibility of the myocardium to early after-depolarizations (EADs) at low heart rates. Antiarrhythmic agents that exhibit reverse use-dependence are more efficacious at preventing a tachyarrhythmia than converting someone into normal sinus rhythm. Because of the reverse use-dependence of class III agents, at low heart rates class III antiarrhythmic agents may paradoxically be more arrhythmogenic.
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Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
s.
Arrhythmia
Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic agents.Mechanism
Class III agents predominantly block the potassium channels, thereby prolonging repolarization. More specifically, their primary effect is on IKrHERG
hERG is a gene that codes for a protein known as Kv11.1 potassium ion channel...
.
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).
Class III antiarrhythmic agents exhibit reverse use dependent prolongation of the action potential duration (Reverse use-dependence). This means that the refractoriness of the ventricular myocyte
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....
increases at lower heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
s. This increases the susceptibility of the myocardium to early after-depolarizations (EADs) at low heart rates. Antiarrhythmic agents that exhibit reverse use-dependence are more efficacious at preventing a tachyarrhythmia than converting someone into normal sinus rhythm. Because of the reverse use-dependence of class III agents, at low heart rates class III antiarrhythmic agents may paradoxically be more arrhythmogenic.
Examples and uses
- AmiodaroneAmiodaroneAmiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
is indicated for the treatment of refractory VTVentricular tachycardiaVentricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...
or VFVentricular fibrillationVentricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest...
, particularly in the setting of acute ischemia. Amiodarone is also safe to use in individuals with cardiomyopathyCardiomyopathyCardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...
and atrial fibrillationAtrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
, to maintain normal sinus rhythm. AmiodaroneAmiodaroneAmiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
prolongation of the action potential is uniform over a wide range of heart rates so this drug does not have reverse use-dependent action. AmiodaroneAmiodaroneAmiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
was the first agent described in this class. Amiodarone should only be used to treat adults with life-threatening ventricular arrhythmias when other treatments are ineffective or have not been tolerated. FDA MedWatch http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm084108.htm
- DofetilideDofetilideDofetilide is a class III antiarrhythmic agent.It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide....
blocks only the rapid K channels; this means that at higher heart rates, when there is increased involvement of the slow K channels, dofetilide has less of an action potential-prolonging effect.
- SotalolSotalolSotalol is a drug used in individuals with rhythm disturbances of the heart, and to treat hypertension in some individuals. It is a non-selective competitive β-adrenergic receptor blocker that also exhibits Class III antiarrhythmic properties by its inhibition of potassium channels...
is indicated for the treatment of atrial or ventricular tachyarrhythmias, and AV re-entrant arrhythmias.
- IbutilideIbutilideIbutilide is a Class III antiarrhythmic agent that is indicated for acute cardioconversion of atrial fibrillation and atrial flutter of a recent onset to sinus rhythm. It exerts its antiarrhythmic effect by induction of slow inward sodium current, which prolongs action potential and refractory...
is the only antiarrhythmic agent currently approved by the Food and Drug AdministrationFood and Drug AdministrationThe Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
for acute conversion of atrial fibrillationAtrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
to sinus rhythm.
- AzimilideAzimilideAzimilide is a class ΙΙΙ antiarrhythmic drug . The agents from this heterogeneous group have an effect on the repolarization, they prolong the duration of the action potential and the refractory period. Also they slow down the spontaneous discharge frequency of automatic pacemakers by depressing...
- BretyliumBretyliumBretylium is an antiarrhythmic agent. It blocks the release of noradrenaline from nerve terminals. In effect, it decreases output from the peripheral sympathetic nervous system. It also acts by blocking K+ channels and is considered a class III antiarrhythmic...
- ClofiliumClofiliumClofilium is an antiarrhythmic agent....
- E-4031E-4031E-4031 is an experimental class III antiarrhythmic drug that blocks potassium channels of the hERG-type.- Chemistry :E-4031 is a synthetized toxin that is a methanesulfonanilide class III antiarrhythmic drug.- Target :...
- NifekalantNifekalantNifekalant is a class III antiarrhythmic agent approved in Japan for the treatment of arrhythmias and ventricular tachycardia. It has the brand name Shinbit....
- TedisamilTedisamilTedisamil is an experimental class III antiarrhythmic agent currently being investigated for the treatment of atrial fibrillation. Tedisamil blocks multiple types of potassium channels in the heart resulting in slowed heart rate...
- SematilideSematilideSematilide is an antiarrhythmic agent....
- Ampyra (recently approved for MS)
Other uses
Potassium channel blockers have also been approved for use in the treatment of multiple sclerosisMultiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
.