Suez Canal University

Faculty of Pharmacy
Pharm D program – 2nd Year
Cardiovascular Assignment
Majid Mahmoud Hussain Al-laithy

K Channel Blockers

HOW DO POTASSIUM CHANNEL BLOCKERS WORK?

Potassium channel blockers are a class of drugs used for treating arrhythmias (improper
beating of the heart, whether irregular, too fast or too slow). They also improve
movement in people with multiple sclerosis.
In multiple sclerosis, the nerve cells do not have myelin sheets (demyelination). As a
result, the potassium channels get exposed, leading to the leakage of potassium ions.
When potassium starts to leak, there is a decrease in the nerve excitability or action
potential, and the communication between the nerve and muscles does not occur. Thus,
the muscles fail to work.
Potassium channel blockers inhibit the potassium channel in the central nervous
system and prolong action potential. They help to improve movement in people with
multiple sclerosis.

HOW ARE POTASSIUM CHANNEL BLOCKERS USED?

Potassium channel blockers are used for treating:

 Arrhythmia
 Movement disorders associated with multiple sclerosis
WHAT ARE SIDE EFFECTS OF POTASSIUM CHANNEL BLOCKERS?

Potassium channel blockers can cause the following side effects:

 Urinary tract infection

 Insomnia
 Headache
 Nausea
 Back pain
 Balance disorder
 Constipation
 Abdominal pain
 Hypertension
 Muscle spasms
 Cataract
 Pain in the legs

Cardiac Side Effects and Contraindications

These drugs, like Class I drugs, are proarrhythmic as well as being antiarrhythmic. For
example, the increase in action potential duration can produce torsades de pointes (a type of
ventricular tachycardia), especially in patients with long-QT syndrome. Amiodarone, because
of its Class IV effects, can cause bradycardia and atrioventricular block, and therefore is
contraindicated in patients with heart block or sinoatrial node dysfunction

Examples

 Amiodarone is indicated for the treatment of refractory VT or VF, particularly in the

setting of acute ischemia.
 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.

Drug Interactions
Interaction of potassium channel openers and blockers
The possibility that the interaction between potassium channel openers, e.g. cromakalim,
pinacidil and nicorandil, and some potassium channel blockers involves a common site was
investigated in canine atrial muscle. Cromakalim, pinacidil and nicorandil produced a negative
inotropic effect.
The potassium channel blockers, tetraethylammonium (TEA), tetrabutylammonium (TBA), 3,4-
diaminopyridine (DAP), CsCl and BaCl2 all produced a positive inotropic effect.
The concentration-effect curves for the negative inotropic actions of pinacidil were shifted in a
parallel way to the right by low concentrations of TEA, TBA or BaCI2. These results suggest the
following: quaternary ammonium compounds like TEA and TBA antagonize the negative
inotropic effect of cromakalim, pinacidil and nicorandil by binding to potassium channels, thus
preventing binding of the channel openers to the same sites or closely related sites in canine right
atrial muscles
The potassium channels responsible for the negative inotropic effects of the three potassium
channel openers seem to be akin to apamin-insensitive and calcium insensitive potassium
channels in smooth muscle and are opened at the resting membrane potential.

o Use NSAIDs with caution in patients at risk for thromboembolism

o Decreased renal excretion: ketoconazole (contraindicated use)

o Not recommended with concurrent use of phenothiazines, tricyclic

antidepressants, SSRIs, macrolide anti- infectives (erythromycin,
clarithromycin), azole antifungals, or other drugs that
inhibit CYP3A4 isoenzymes

o Contraindicated with cimetidine, trimethoprim, ketoconazole, prochlorperazine,

megestrol, or verapamil
 o Angioedema, bradycardia, cerebral ischemia, facial paralysis, and serious
ventricular arrhythmias or various forms of heart block may be noted.

Benefits in Clinical use

 Potassium Channel Blockade Enhances Atrial Fibrillation-Selective Antiarrhythmic
Effects of Optimized State-Dependent Sodium Channel Blockade

 Improve movement in people with multiple sclerosis

 Terminates reentrant tachyarrhythmias, preventing reinduction.

 Maintenance of normal sinus rhythm in patients with atrial fibrillation or atrial

flutter longer than 1 week duration, who have been converted to normal sinus rhythm

References

https://cdnsciencepub.com/doi/10.1139/cjpp-2017-0024

https://cvpharmacology.com/antiarrhy/potassium-blockers

https://go.drugbank.com/categories/DBCAT000519

https://www.ahajournals.org/doi/full/10.1161/circulationaha.115.018016
https://www.sciencedirect.com/topics/medicine-and-dentistry/potassium-channel-
blocker

https://www.rxlist.com/potassium_channel_blockers/drug-
class.htm#:~:text=Potassium%20channel%20blockers%20inhibit%20the,in%20pe
ople%20with%20multiple%20sclerosis.