Potassium channel blockers are agents which interfere with conduction through

potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of c ...

Medical uses

Arrhythmia

Potassium channel blockers used in the treatment of

cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...

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 I_Kr. Since these agents do not affect the

sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chan ...

, 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).

Examples and uses

Amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibril ...

is indicated for the treatment of refractory VT or VF, particularly in the setting of acute ischemia. Amiodarone is also safe to use in individuals with

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. ...

and atrial fibrillation, to maintain normal sinus rhythm. Amiodarone prolongation of the action potential is uniform over a wide range of heart rates, so this drug does not have reverse use-dependent action.

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. *

Dofetilide Dofetilide 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. It is not available in Europe or Australia. ...

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. * Sotalol is indicated for the treatment of atrial or ventricular tachyarrhythmias, and

AV re-entrant arrhythmia Supraventricular tachycardia (SVT) is an umbrella term for fast heart rhythms arising from the upper part of the heart. This is in contrast to the other group of fast heart rhythms – ventricular tachycardia, which start within the lower cham ...

s. * Ibutilide is the only antiarrhythmic agent currently approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

for acute conversion of atrial fibrillation to sinus rhythm. * Azimilide * Bretylium * Clofilium *

E-4031 E-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 E-4031 acts on a specif ...

* Nifekalant * Tedisamil * Sematilide

Side effects

These agents include a risk of

torsades de pointes ''Torsades de pointes, torsade de pointes'' or ''torsades des pointes'' (TdP) (, , translated as "twisting of peaks") is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorphic ventricular tachycardia t ...

Anti-diabetics

Sulfonylureas Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...

, such as

gliclazide Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti-diabetic medication, used to treat type 2 diabetes. It is used when dietary changes, exercise, and weight loss are not enough. It is taken by mouth. ...

, are

ATP-sensitive potassium channel An ATP-sensitive potassium channel (or KATP channel) is a type of potassium channel that is gated by intracellular nucleotides, ATP and ADP. ATP-sensitive potassium channels are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR ...

blockers.

Other uses

Dalfampridine, A potassium channel blocker has also been approved for use in the treatment of

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...

Reverse use dependence

Potassium channel blockers exhibit reverse use-dependent prolongation of the action potential duration. Reverse use dependence is the effect where the efficacy of the drug is reduced after repeated use of the tissue. This contrasts with (ordinary) use dependence, where the efficacy of the drug is increased after repeated use of the tissue. Reverse use dependence is relevant for potassium channel blockers used as class III antiarrhythmics. Reverse use dependent drugs that slow heart rate (such as

quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

) can be less effective at high heart rates. The refractoriness of the ventricular

myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a mus ...

increases at lower

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...

s. This increases the susceptibility of the myocardium to early Afterdepolarizations (EADs) at low heart rates. Antiarrhythmic agents that exhibit reverse use-dependence (such as

) 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. Drugs such as quinidine may be both reverse use dependent and use dependent.

Calcium-activated channel blockers

Examples of calcium-activated channel blockers include: *

Charybdotoxin Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion '' Leiurus quinquestriatus hebraeus'' (''deathstalker'') that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous sys ...

* Iberiotoxin * Apamin * Kaliotoxin, * Lolitrem, * BK_Ca-specific ** GAL-021 ** Ethanol (alcohol)

Inwardly rectifying channel blockers

Examples of inwardly rectifying channel blockers include:

ROMK (K_ir1.1)

Nonselective: Ba²⁺, Cs⁺

GPCR regulated (K_ir3.x)

GPCR G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

antagonists * Ifenprodil * Caramiphen *

Cloperastine Cloperastine (INN) or cloperastin, in the forms of cloperastine hydrochloride ( JAN) (brand names Hustazol, Nitossil, Seki) and cloperastine fendizoate (or hybenzoate), is an antitussive and antihistamine that is marketed as a cough suppressant i ...

Clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

Dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with b ...

Ethosuximide Ethosuximide, sold under the brand name Zarontin among others, is a medication used to treat absence seizures. It may be used by itself or with other antiseizure medications such as valproic acid. Ethosuximide is taken by mouth. Ethosuximide i ...

* Tertiapin *

Tipepidine Tipepidine (INN) (brand names Asverin, Antupex, Asvelik, Asvex, Bitiodin, Cofdenin A, Hustel, Nodal, Sotal), also known as tipepidine hibenzate ( JAN), is a synthetic, non-opioid antitussive and expectorant of the thiambutene class. It acts as ...

* Ba²⁺

ATP-sensitive (K_ir6.x)

Meglitinide Meglitinides or glinides are a class of drugs used to treat type 2 diabetes. Drugs Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997. Other drugs in this class include nateglinide (Starlix) and mitiglin ...

s (Non-

Sulfonylurea Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the bet ...

s) ** Mitiglinide ** Nateglinide **

Repaglinide Repaglinide is an antidiabetic drug in the class of medications known as meglitinides, and was invented in 1983. Repaglinide is an oral medication used in addition to diet and exercise for blood sugar control in type 2 diabetes mellitus. The mec ...

s ** Acetohexamide ** Carbutamide **

Chlorpropamide Chlorpropamide is a drug in the sulfonylurea class used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea. Mechanism of action Like other sulfonylureas, chlorpropamide acts to increase the secretion of insulin, ...

** Glycyclamide ** Metahexamide *

s (continued) ** Tolazamide ** Tolbutamide **

Glibornuride Glibornuride ( INN) is an anti-diabetic drug from the group of sulfonylureas. It is manufactured by MEDA Pharma and sold in Switzerland under the brand name Glutril. Synthesis Gliburnide is an endo-endo derivative made from camphor-3-carboxam ...

Glisoxepide Glisoxepide (INN) is an orally available anti-diabetic drug from the group of sulfonylurea Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the ...

** Glyclopyramide **

Gliclazide Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti-diabetic medication, used to treat type 2 diabetes. It is used when dietary changes, exercise, and weight loss are not enough. It is taken by mouth. ...

** Glibenclamide (glyburide) ** Glipizide **

Glimepiride Glimepiride, is an anti-diabetic medication used to treat type 2 diabetes. It is less preferred than metformin. Use is recommended together with diet and exercise. It is taken by mouth. Glimepiride takes up to three hours for maximum effect and l ...

** Glicaramide

Tandem pore domain channel blockers

Examples of tandem pore domain channel blockers include: *

Bupivacaine Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease feeling in a specific area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space. I ...

Quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

Fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive diso ...

* Seproxetine (Norfluoxetine) * 12-''O''-tetradecanoylphorbol-13-acetate (TPA) (phorbol 12-myristate 13-acetate).

Voltage-gated channel blockers

Examples of voltage-gated channel blockers include: *Some types of dendrotoxins * 3,4-Diaminopyridine (amifampridine) * 4-Aminopyridine (fampridine/dalfampridine) * Adekalant * Almokalant *

Amiodarone also blocks

CACNA2D2 Voltage-dependent calcium channel subunit alpha2delta-2 is a protein that in humans is encoded by the ''CACNA2D2'' gene. This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. ...

-containing

voltage gated calcium channel Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabil ...

s * Azimilide * Bretylium * Bunaftine *

* Clamikalant * Conotoxins, such as κ-conotoxin, * Dalazatide *

works by selectively blocking the rapid component of the

delayed rectifier outward potassium current Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized ce ...

(I_Kr) * Dronedarone,Guillemare E, Marion A, Nisato D, Gautier P, “Inhibitory effects of dronedarone on muscarinic K+ current in guinea pig atrial cells,” in Journal of Cardiovascular Pharmacology, 2000 7 *

blocks

s of the hERG-type * GuangxitoxinPrimarily inhibits outward voltage-gated K_v2.1

currents Currents, Current or The Current may refer to: Science and technology * Current (fluid), the flow of a liquid or a gas ** Air current, a flow of air ** Ocean current, a current in the ocean *** Rip current, a kind of water current ** Current (stre ...

. * Hanatoxin * HgeTx1 * HsTx1 a very potent inhibitor of the rat Kv1.3

voltage-gated potassium channel Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized c ...

* Ibutilide, * Inakalant * Kaliotoxin * Linopirdine * Lolitrem B *

Maurotoxin Maurotoxin (abbreviated MTX) is a peptide toxin from the venom of the Tunisian chactoid scorpion ''Scorpio maurus palmatus'', from which it was first isolated and from which the chemical gets its name. It acts by blocking several types of vol ...

* Nifekalant * Notoxin *

Paxilline Paxilline is a toxic, tremorgenic diterpene indole polycyclic alkaloid molecule produced by '' Penicillium paxilli ''which was first characterized in 1975. Paxilline is one of a class of tremorigenic mycotoxins, is a potassium channel blocker, ...

* Pinokalant *

* ShK-186 * Sotalol * Tedisamil * Terikalant * TetraethylammoniumB. Hille (1967). "The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ions." ''J. Gen. Physiol.'' 50 1287-1302.C. M. Armstrong (1971). "Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons." ''J. Gen. Physiol.'' 58 413-437. * Verapamil, * Vernakalant

hERG hERG (the human '' Ether-à-go-go''-Related Gene) is a gene () that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel. This ion channel (sometimes simply denoted as 'hERG') is best known for its contribution to t ...
(KCNH2, K_v11.1)-specific

Ajmaline Ajmaline (also known by trade names Gilurytmal, Ritmos, and Aritmina) is an alkaloid that is classified as a 1-A antiarrhythmic agent. It is often used to induce arrhythmic contraction in patients suspected of having Brugada syndrome. Individuals ...

AmmTX3 AmmTX3, produced by ''Androctonus mauretanicus'', is a scorpion toxin of the α-KTX15 subfamily. The toxin is known for its ability to act as a specific Kv4 channel blocker, and thereby reducing the A-type potassium current through this channel. ...

Astemizole Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It was withdrawn from the m ...

Azaspiracid Azaspiracids (AZA) are a group of polycyclic ether marine algal toxins produced by the small dinoflagellate '' Azadinium spinosum'' that can accumulate in shellfish and thereby cause illness in humans. Azaspiracid was first identified in the 1990 ...

* AZD1305 * Azimilide *

Bedaquiline Bedaquiline, sold under the brand name Sirturo, is a medication used to treat active tuberculosis. Specifically, it is used to treat multi-drug-resistant tuberculosis (MDR-TB) along with other medications for tuberculosis. It is used by mouth. ...

* BeKm-1 * BmTx3 * BRL-32872 *

Chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...

Cisapride Cisapride is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors in ...

Clarithromycin Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, '' H. pylori'' infection, and Lyme disease, among others. Clarith ...

* Darifenacin *

Dextropropoxyphene Dextropropoxyphene is an analgesic in the opioid category, patented in 1955 and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive (cough suppressant) ...

Diallyl trisulfide Diallyl trisulfide (DATS), also known as Allitridin, is an organosulfur compound with the formula S(SCH2CH=CH2)2. It is one of several produced by the hydrolysis of allicin, including diallyl disulfide and diallyl tetrasulfide, DATS is one of th ...

Domperidone Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis (delayed gastric emptying). It raises the l ...

* Ergtoxins *

Erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used durin ...

* Gigactonine *

Haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

Ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...

* Norpropoxyphene *

Orphenadrine Orphenadrine (sold under many brand names) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control i ...

Pimozide Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis ...

* PNU-282,987 *

Promethazine Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...

Ranolazine Ranolazine, sold under the brand name Ranexa among others, is a medication used to treat heart related chest pain. Typically it is used together with other medications when those are insufficient. Benefits appear smaller in women than men. It ...

* Roxithromycin *

Sertindole Sertindole, sold under the brand name Serdolect among others, is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, i ...

Solifenacin Solifenacin, sold as the brand name Vesicare among others, is a medicine used to treat overactive bladder and neurogenic detrusor overactivity (NDO). It may help with incontinence, urinary frequency, and urinary urgency. Benefits appear simi ...

* Tamulotoxin * Terodiline * Terfenadine *

Thioridazine Thioridazine (Mellaril or Melleril) is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwid ...

* Tolterodine * Vanoxerine * Vernakalant

KCNQ (K_v7)-specific

* Linopirdine * XE-991 * Spooky toxin (SsTx)

Notes

References

{{Antiarrhythmic agents