potassium channel blocker potassium channel blocker potassium channel blockers are agents which interfere with conduction through potassium channels. tetraethylammonium is a commonly used potassium channel blocker medical uses arrhythmia effect of class iii antiarrhythmic agent on cardiac action potential. 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 ikr. 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. amiodarone should only be used to treat adults with life-threatening ventricular arrhythmias when other treatments are ineffective or have not been tolerated. 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. sotalol is indicated for the treatment of atrial or ventricular tachyarrhythmias, and 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 tedisamil sematilide side effects these agents include a risk of torsades de pointes. anti-diabetics sulfonylureas, such as gliclazide, are atp-sensitive potassium channel blockers. other uses dalfampridine, a potassium channel blocker has also been approved for use in the treatment of multiple sclerosis. 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) can be less effective at high heart rates. the refractoriness of the ventricular myocyte increases at lower heart rates. this increases the susceptibility of the myocardium to early afterdepolarizations (eads) at low heart rates. antiarrhythmic agents that exhibit reverse use-dependence (such as quinidine) 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 potassium channel blockers examples of calcium-activated potassium channel blockers include: charybdotoxin iberiotoxin apamin kaliotoxin, lolitrem, bkca-specific gal-021 ethanol (alcohol) inwardly rectifying channel blockers examples of inwardly rectifying channel blockers include: romk (kir1.1) nonselective: ba2+, cs+ gpcr regulated (kir3.x) gpcr antagonists ifenprodil caramiphen cloperastine clozapine dextromethorphan ethosuximide tertiapin tipepidine ba2+ atp-sensitive (kir6.x) meglitinides (non-sulfonylureas) mitiglinide nateglinide repaglinide sulfonylureas acetohexamide carbutamide chlorpropamide glycyclamide metahexamide sulfonylureas (continued) tolazamide tolbutamide glibornuride glisoxepide glyclopyramide gliclazide glibenclamide (glyburide) glipizide glimepiride glicaramide tandem pore domain channel blockers examples of tandem pore domain channel blockers include: bupivacaine quinidine fluoxetine 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 azimilide bretylium bunaftine charybdotoxin clamikalant conotoxins, such as κ-conotoxin, dalazatide dofetilide dronedarone, e-4031 guangxitoxin hanatoxin hgetx1 hstx1 ibutilide, inakalant kaliotoxin linopirdine lolitrem b maurotoxin nifekalant notoxin paxilline pinokalant quinidine shk-186 sotalol tedisamil terikalant tetraethylammonium verapamil, vernakalant herg (kcnh2, kv11.1)-specific ajmaline amiodarone ammtx3 astemizole azaspiracid azd1305 azimilide bedaquiline bekm-1 bmtx3 brl-32872 chlorpromazine cisapride clarithromycin darifenacin dextropropoxyphene diallyl trisulfide domperidone e-4031 ergtoxins erythromycin gigactonine haloperidol ketoconazole norpropoxyphene orphenadrine pimozide pnu-282,987 promethazine quinidine ranolazine roxithromycin sertindole solifenacin tamulotoxin terodiline terfenadine thioridazine tolterodine vanoxerine vernakalant kcnq (kv7)-specific linopirdine xe-991 spooky toxin (sstx)