Antiarrhythmic Medications

last authored:
last reviewed:






Organized electrical activity of the heart plays a significant role in cardiac function, and disruption of this activity in the form of arrythmias may result in clinical symptoms or even death. These arrythmias may be too fast - tachyarrythmias - or to slow - bradyarrhythmias.


Antiarrhytmic drugs work in two main ways. They may impact the ion channels that cause and regulate the heart beat, including sodium, potassium, and calcium. They may also modify the neuronal control of the heart, particularly the beta adrenergic innervation of the sympathetic nervous system.


Unfortunately, while antiarrythmic drugs are meant to bring normalcy to the heart beat, on occasion, the opposite may occur, and they may in fact cause arrythmias. This is particularly true for the sodium channel blocking drugs.

return to top





Antiarrhythmic medications have a number of uses, including:

return to top





There are many ways to classify antiarrhythmic medications.

One of the most common, to be used here, is the Vaughan-Williams classification, which is organized according to the mechanism of action. These mechanisms include:

However, this is an inexact classification, as many medications have numerous sites of action.



Common Medications

  • Class I
  • Class II
  • Class III
  • Class IV
  • Other

Class I

Class I medications, which block sodium channels, are further subdivided into three categories.


Class Ia medications slow the rise of phase 0 of the action potential, therefore slowing conduction velocity. They also prolong the ventricular refractory period, as well as slow the depolarization of phase 4 of pacemaker cells. Class Ia medications include:

  • quinidine
  • procainamide
  • disopyramide


Class Ib medications slow the conduction, and shorten the action potential, of healthy tissue. Class Ib medications include:

  • lidocaine
  • phenytoin

Class Ic medications slow the rise of phase 0 of the action potential, as well as shorten the refractory period of Purkinje fibres. Class Ic medications include:

  • flecainide
  • propafenone

Class II


Beta blockers

  • inhibit sympathetic innervation, slowing HR, decreasing conduction velocity through AV node, and increasing refractory period
  • metoprolol

Increase action pulse duration

  • work by increasing refractory period
  • leads to two-way block
  • many of these drugs block K+ channels involved in repolarizing
  • amiodarone
  • blocks inactivated sodium channels, increasing calcium
  • prolongs AP by blocking potassium channels
  • decreases HR and AV node conduction
  • excreted in epithelial cells, so long half-life
  • metabolized in liver to bioactive by C3A4
  • inhibits cytochrome P450 cytochromes, increasing lvels of drugs such as cyclosporine, warfarin


Calcium channel blocker

  • verapamil
  • diltiazem


  • decrease AV node velocity and increase refractory period
  • digoxin
  • adenosine


Bradycardia due to a damaged SA node can be treated with:

  • atropine, a muscarinic blocker that increases transmission rate
  • epinephrine or dobutamine to stimulate β1 receptors



Contains large amounts of iodine

  • acute GI distress
  • phlebitis


long term

  • hepatic fibrosis
  • pulmonary fibrosis
  • hypothyroidism
  • hyperthyroidism

Class III





Amiodarone is an atiarrhythmic drug, acting on sodium, potassium, and calcium channels, and with alpha- and beta-adrenergic blocking capacity. It comes with many substantial side effects, and should be used only in life-threatening situations by people well-versed in its use.




Class IV


CCBs are used for

  • hypertension (combine with ACE/ARB and beta blockers)
  • stable angina
  • in ACS, generally only used acutely for ongoing ischemia when beta-blockers are contraindicated


Calcium channel blockers are negative inotropes, blocking Ca2+ influx into vascular smooth muscle cells and cardiomyocytes. This leads to:

  • slowed heart rate (decrease AV node velocity and increase refractory period)
  • coronary/peripheral vasodilation
  • decreased contractility
  • MVO2
  • decreased afterload
  • decreases vasospasms

The two classes of CCBs are



  • nifedipine (primarily VSMCs)
  • amliodipine


  • verapamil, diltiazem (acts on cardiomyocytes and VSMCs )
  • will slow down the heart rate and contractility

Guidance for use

  • Avoid short acting dihydropyridines, ie nifedipine, due to its drop in BP
  • non-dihydropyridines (verapamil and diltizaem) are negatively chronotropic and should generally be avoided in patients with poor LV function or HF

can cause headaches, flushing, dizziness

peripheral edema

constipation (verapamil)

bradycardia/heart block (verapamil, diltiaezm)

worsening heart failure




Digoxin is a cardiac glycoside used to increase cardiac contractility.

Digoxin is one of the few drugs whose levels can be monitored. Use low doses (0.0625 or 0.125) if necessary.



DIG trial (NEJM, 1997): no benefit for mortality; lower hospitalization rates. However, may be high levels of mortality in women.



  • inhibits the cardiac Na-K ATPase
  • increase [Na] inside
  • the Na/Ca exchanger increase intracellular [Ca], leading to increased contraction
  • increased contractility increases cardiac output


Adverse Effects

  • can lead to increased ACh release in the AV node, leading to increased refractory period and potentially to AV block and cardiac arrest
  • can cause arrhythmias
  • can cause hypokalemia

Digoxin Toxicity

  • visual changes in 10-25%: changes in colour vision yellow/green, red/blue, hazy vision halos
  • neuropsychiatric: 5-10%
  • narrow therapeutic index - 2-3 x of a therapeutic dose can be toxic

Digoxin withdrawal has been shown be safe in many patients (PROVED study, RADIANCE study). However, patients do worse if they have:

  • congestive symptoms
  • worse ventricular function
  • no ACE inhibitor


return to top




Guidance on Use


return to top




Resources and References


return to top