Potassium channel blocker

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Potassium channel blockers are agents which interfere with conduction through potassium channels.

Medical uses

Arrhythmia

Potassium channel blockers used in the treatment of

Mechanism

Class III agents predominantly block the potassium channels, thereby prolonging repolarization.^[1] More specifically, their primary effect is on I_Kr.^[2]

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).

Examples and uses

• Amiodarone 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 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. Amiodarone was the first agent described in this class.^[3] Amiodarone should only be used to treat adults with life-threatening ventricular arrhythmias when other treatments are ineffective or have not been tolerated.^[4]
• 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.
• AV re-entrant arrhythmias
  .
• Ibutilide is the only antiarrhythmic agent currently approved by the Food and Drug Administration for acute conversion of atrial fibrillation to sinus rhythm.
• Azimilide
• Bretylium
• Clofilium
• E-4031
• Nifekalant^[5]
• Tedisamil
• Sematilide

Side effects

These agents include a risk of torsades de pointes.^[6]

Anti-diabetics

A study appears to indicate that topical spray of a selective Tandem pore Acid-Sensitive K+ (TASK 1/3 K+) (potassium antagonist) increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and obstructive sleep apnoea (OSA). [8] ^[9]

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.^[10] 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

Drugs such as quinidine may be both reverse use dependent and use dependent.[10]

Calcium-activated potassium channel blockers

Examples of calcium-activated potassium channel blockers include:

• Charybdotoxin^{[11][12][13][14]}
• Iberiotoxin^[15]
• Apamin^[16][14]

• Kaliotoxin,^[17][18]

• Lolitrem,^[19]

• BK_Ca-specific
  • GAL-021^[20]
  • Ethanol (alcohol)^[21]

Inwardly rectifying channel blockers

Examples of

ROMK (K_ir1.1)

Nonselective: Ba²⁺,^[22] Cs^+[23]

GPCR regulated

(K_ir3.x)

• example needed
  ]
• Ifenprodil^[24]
• Caramiphen ^{[citation needed]}
• Cloperastine^[25][26][27]
• Clozapine ^{[citation needed]}
• Dextromethorphan ^{[citation needed]}
• Ethosuximide ^{[citation needed]}
• Tertiapin^[28][14]
• Tipepidine^[29]
• CGP-7930^[30]
• Ba^2+[22]

ATP-sensitive

(K_ir6.x)

Tandem pore domain channel blockers

Examples of

• Bupivacaine^{[33][34][35][36]}
• Quinidine^{[34][37][38][39][40]}
• Fluoxetine^[41]
• Seproxetine (Norfluoxetine)^[41]
• 12-O-tetradecanoylphorbol-13-acetate (TPA) (phorbol 12-myristate 13-acetate).^[42]

Voltage-gated channel blockers

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Examples of voltage-gated channel blockers include:

hERG (KCNH2, K_v11.1)-specific

KCNQ (K_v7)-specific

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

See also

• Potassium channel
• Potassium channel opener

Notes