Class I
Class I antiarrhythmics work on this phase of the cardiac action potential.
What is Phase 0 (Na+ channel blockade)?
- Class Ib inhibit the weakest and class Ic inhibit the strongest.
- Class Ia will also prolong repolarization and Ib will shorten it. No effect from Ic.
Beta-blockers primarily act at this cardiac structure.
What is the AV node?
- Work by slowing Phase 4 depolarization at the AV node and thus slowing conduction.
- Cardioselective (beta-1) cause decreased HR, cardiac contractility and workload, thus reducing overall stress on the heart.
Class III antiarrhythmics work on ion channels of this electrolyte.
What are potassium channels?
- K+-channel blockade during phase 3 of the action potential leads to prolonged repolarization and thus increases tissue refractoriness
- Increasing refractoriness also blocks reentry wave fronts.
Class IV antiarrhythmics primarily work on this type of ion channel.
What are calcium channels?
- Primary activity at the SA and AV nodes to slow depolarization and thus conduction.
- Primarily used for supraventricular tachyarrhythmias (AFib/flutter, SVT, AVRT, AVNRT, etc).
- Will see PR prolongation on ECG.
- Similar to class I drugs, they exhibit "use-dependence" (increase in the calcium channel blockade as HR increases).
This medication is given as a rapid push to terminate both stable and unstable supraventricular tachyarrhythmias.
What is adenosine?
- Works by slowing conduction through the AV node, interrupting re-entry pathways through the AV node, and restoring normal sinus rhythm.
- Can also be used diagnostically to delineate underlying rhythm of rapid narrow-complex arrhythmias.
- Give 6mg push over 1-2 seconds, then flush. Can repeat dose at 12mg after 1-2 minutes, then finally 12-18mg if does not terminate the arrhythmia or cause AV block.
- Always good to warn the patient that it may be unpleasant before pushing!
These are the two antiarrhythmics in the class Ic category.
What are propafenone and flecanide?
- Both are contraindicated in structural and ischemic heart disease.
- Due to significant proarrhythmogenicity, usually EP will be starting these with in-hospital monitoring for loading.
- Both are used for maintenance of sinus rhythm in AFib/flutter and SVT, as well as for pharmacological cardioversion. Propafenone can also be used for NSVT and PVCs (not sustained VT). Flecainide may be used for sustained VT but not recommended in NSVT/PVCs due to proarrhythmogenicity.
This cardioselective beta-blocker is commonly given IV or PO to achieve rate control in Afib.
What is metoprolol?
- IV should be used with caution, especially in those with low BP or Hx of heart failure, and should NOT be used in those with decompensated HFrEF (HFpEF use caution).
- Metoprolol IV usually given as 5 mg pushes (max 15 mg), whereas PO usually tartrate 25 mg BID.
- Beta-blockers, when compared to CCB, have the largest decrease in mortality as a rate-controlling agent in AFib.
- Metoprolol tartrate is shorter-acting and is more used when titrating in the hospital. Succinate is longer-acting a dosed once daily.
This commonly used drug has activity of all four antiarrhythmic classes.
What is amiodarone?
- Exact mechanism not completely understood. Unlike other class III drugs, amiodarone has very little proarrhythmic activity.
- Very widely used for the treatment of both ventricular and atrial arrhythmias, though long-term use is limited by significant toxicity.
- Amiodarone is the most effective medical therapy available for maintaining sinus rhythm.
- For those receiving long-term amiodarone, its important to get baseline PFTs, LFTs, thyroid studies, ECGs, eye and skin exams. Should be re-evaluated at least every 6 months.
This class IV antiarrhythmic is commonly given for rate control in AFib with RVR.
What is diltiazem?
- Should only be used in hemodynamically stable patients!
- Bolus dose: 0.25 mg/kg (actual body weight) over 2 minutes, can repeat bolus at 0.35 mg/kg if not controlled after 15 min. After that can start gtt at 5-10 mg/hour and titrate up in 5 mg/hour increments to a max of 15 mg/hour.
- Diltiazem has more vasodilatory effect when compared to other class IV antiarrhythmics.
- Can also be used to treat vasospastic angina in addition to PRN nitroglycerin.
- Main side effects: Peripheral edema, dizziness, dyspepsia.
This medication, while not an antiarrhythmic, is crucial for the treatment of polymorphic VT.
What is magnesium sulfate?
- Usually bolus dose of 1-2 grams IV over 15 minutes followed by infusion.
- Suppress early afterdepolarizations (EADs) to terminate the arrhythmia.
- Blocks calcium channels during repolarization -> decreases calcium influx and lowers the amplitude of EADs.
- Slow cardiac conduction through the AV node -> decreases the QT interval and increases the refractory period.
- Highly effective for treatment and preventing recurrence of long QT-related ventricular ectopy that triggers TdP.
This anti-arrhythmic is also used to treat malaria and can paradoxically cause arrhythmias (eg, torsades).
What is quinidine?
- Class Ia medication used to prevent ventricular arrhythmias (eg, sustained VT, Brugada) as well as pharmacolocical conversion in AFib and maintaining NSR.
- Side effects: cinchonism (blurry vision, tinnitus, headache) and GI upset (nausea, vomiting, diarrhea)
- Most class Ia medications can cause anticholinergic side effects (Eg, dry mouth, blurry vision, urinary hesitancy, constipation, etc.)
- Fun fact: This medication was derived from a compound in the bark of the cinchona tree.
This medication is used as the mainstay of treatment in beta-blocker toxicity.
What is glucagon?
- Intravenous (IV) glucagon is given as a slow bolus dose followed continuous infusion. An initial bolus of 5 mg IV over 1 min; if there is no increase in pulse or blood pressure after 10 to 15 minutes, give a second bolus.
- If there is no observed effect after 10 minutes following a second dose, it is unlikely an infusion will provide benefit. Otherwise, drip at 2 to 5 mg/hour.
- Works by increasing cAMP and thus increases the intracellular pool of calcium available for release during depolarization, augmenting contractility.
This drug is a relative of amiodarone that has much lower risk of toxicity.
What is dronedarone?
- Does not contain iodine molecule which is thought to be why less toxic. Also has much shorter half-life (24 hours) compared to amiodarone (50 days).
- Clinical trials have shown the clinical use and short-term safety (up to 21 months) of dronedarone for the maintenance of sinus rhythm following cardioversion in patients with AF.
- Approved for maintenance of sinus rhythm in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation.
- Lower rates of chemical cardioverison compared to amiodarone (<10% of patients).
- Also unlike amiodarone, there is no role for dronedarone in the treatment of ventricular tachyarrhythmias.
Class IV antiarrhythmics are differentiated from their antihypertensive cousins in that they are NOT derived from this molecule.
What is dihydropyridine (non-dihydropyridine)?
- Dihydropyridine CCB (eg, amlodipine, clevidipine, nifedipine) primarily affect vascular smooth muscle causing vasodilation and decreased vascular resistance.
- The antiarrhythmics are derived from phenylalkylamine or benzothiazepine, which are less-selective for vascular SM and more-so for cardiac tissue.
This medication is used in the treatment of unstable or symptomatic bradycardia.
What is atropine?
- Given as 1 mg push every 3-5 minutes for max of 3 mg.
- Avoid with bradycardia caused by hypothermia (hypothermic bradycardia is a direct consequence of slowed cellular metabolism in the heart's pacemaking centers)
- In most cases, will not be effective for second-degree block type 2 or complete heart block (problem is in the His-Purkinje system, below the AV node).
This anti-arrhythmic works similarly to lidocaine, but is orally active.
What is mexiletine?
- Used primarily to treat ventricular tachyarrhythmias (eg, VT) particularly when in the setting of long QT syndrome, as well as PVCs.
- Usually given as 400mg loading dose, then 200mg Q8H if rapid control of arrhythmia needed. Otherwise can to 200mg Q8H. Can do Q12H dosing if appropriate response at lower doses (<300mg Q8H).
- Main side effects: GI upset, chest pain, headache, drowsiness, visual changes (blurry vision).
This non-selective beta-blocker is commonly used in HFrEF and also exhibits a1 antagonism.
What is carvedilol (Coreg)?
- Usually given as a twice-daily medication, it can be used to maintain rate control in AFib/flutter as well as non-sustained VT and PVCs.
- Common side effects: headache, fatigue, weakness, nausea, and diarrhea.
- Shown to reduce risk of death, hospitalization, and recurrent heart attacks in those with HFrEF.
- Caution with use in acute decompensated heart failure.
This class III antiarrhythmic can cause significant QT prolongation, and has properties of class II as well.
What is sotalol?
- Used to treat severe ventricular arrhythmias, and maintenance of sinus rhythm for patients with symptomatic atrial fibrillation (AF) and atrial flutter.
- Dual activity relates to presence of d and l isomers. The d-isomer prolongs repolarization by blocking IKr, and the l-isomer has both class II and III activity.
- QT-prolongation is reverse use dependent, meaning as the heart rate slows, the QT interval prolongs.
- Generally well tolerated, being discontinued because of side effects in approximately 15 percent of patients. The major causes for intolerance are fatigue, bradycardia, dyspnea, proarrhythmia, dizziness and asthenia.
This class IV antiarrhythmic is more commonly used in multifocal atrial tachycardia when rate-control is needed.
What is verapamil?
- Reduces the degree of atrial ectopy and limits the transmission of beats through the AV node to a greater degree than diltiazem.
- Verapamil has stronger selectivity for cardiac tissue when compared to diltiazem.
- Should be avoided in patients with LV dysfunction and acute decompensated HF, as it may worsen pulmonary edema and hypotension.
- Main side effects: Headache, constipation, dyspepsia, lethargy, peripheral edema.
This plant-derived medication is effective for rate-controlling treatment of AFib/flutter, as well as increasing contractility in patients with heart failure
What is digoxin?
- Suppression of the AV node to increase refractory period and decrease conduction velocity. Positive inotropic effect, enhanced vagal tone, and decreased ventricular rate to atrial tachyarrhythmias.
- Use is often reserved for those whose rate has not adequately been controlled with other agents or interventions.
- Needs dose-adjustment in renal impairment (1/3rd to 1/2 normal dose).
- Hypokalemia and hypomagnesemia increase proarrhythmogenicity.
- Narrow therapeutic window, needs monitoring!
- Side effects: GI upset, visual disturbances (“halos,” yellow or blurred vision), lethargy, atrial tachycardia, atrioventricular (AV) block (all types)
This class Ia anti-arrhythmic has a well-known group of side effects commonly including polyarthralgias, myalgias, fevers and pleurisy.
What is procainamide?
- Commonly referred to as a Lupus-like syndrome.
- This drug is commonly used to treat WPW. Also used for ventricular arrhythmias (Eg, sustained VT), peri-arrest wide-complex tachycardias, and SVT unresponsive to AV-nodal blocking agents.
- Should be initiated in a hospital setting.
- Black box warning of leukopenia and agranulocytosis.
These two beta-blockers can be given intravenously in the treatment of hypertensive emergency.
What are esmolol and labetalol?
- Esmolol is β1-selective, whereas labetalol is a non-selective beta-blocker with a1-antagonism.
- Rapid-acting and can be given as both a bolus and infusion.
- Especially useful in hypertensive emergency in cases of aortic dissection, ACS, stroke and hypertensive encephalopathy (labetalol).
- Labetalol is better for use in pregnancy (decreases proteinuria/preeclampsia and fetal/newborn death).
This drug is primarily used to terminate AFib/flutter and prevent recurrence, though is also used off-label for treatment of ventricular tachyarrhythmias and SVT.
What is dofetilide?
- Like other class III agents, dofetilide exhibits reverse use dependency.
- Dosed orally between 125 to 500 mcg twice daily. Due to significant QT prolongation, also requires inpatient initiation. No IV formulation in USA.
- Renally eliminated, so must be dose-adjusted in CKD and renal function can preclude use.
- Dofetilide does not have a negative inotropic effect on left ventricular contractility, so good for use in class II or III heart failure or prior MI.
This vital sign can help differentiate between an overdose with a dihydropyridine versus nondihydropyridine CCBs.
What is bradycardia?
- Dihydropyridine CCB toxicity will have hypotension and reflex tachycardia, where as nondihydropyridine will have hypotension and bradycardia.
- Due to primarily negative inotropic effects of NDHP CCBs.
- Testing: ECG, POC glucose, serum electrolytes, blood urea nitrogen (BUN), creatinine, calcium, and CXR if signs of pulmonary edema, hypoxia, or respiratory distress.
- Treatment: IV fluids, atropine, calcium salts, glucagon.
This medication works by modulating the SA pacemaker "f-current" (If) and is used as an adjunct medication in symptomatic HFrEF and inappropriate sinus tachycardia.
What is ivabradine?
- Consider in patients who are persistently symptomatic despite an optimal GDMT for HFrEF.
- Usually stable, euvolemic patients in sinus rhythm with resting heart rate ≥70 beats per minute (bpm) despite maximally tolerated dose of beta blocker or if there is a contraindication to beta-blocker use.
- Side effects: Bradycardia, hypertension, increased risk of AFib, and visual symptoms (phosphenes).