Antiarrhythmics

Lidocaine and Mexiletine (Class IB)

(8)

• Lidocaine is a widely used antiarrhythmic and local anesthetic. 
• It is only used IV for treating arrhythmias because of rapid first-pass metabolism. 
• Mexiletine is lidocaine's orally active congener. 
• Both are used to treat acute, life-threatening ventricular arrhythmias. 
• Although lidocaine has long been the first choice for treating ventricular arrhythmias, ECC/AHA 2000 guidelines for cardiopulmonary resuscitation recommend IV amiodarone before lidocaine for treatment of ventricular fibrillation or pulseless ventricular tachycardia. 
• Mexiletine does not prolong QT interval and can be used in patients with a history of torsades or DILQTs. 
• Lidocaine is ineffective for prophylaxis of arrhythmias in post-MI patients.
• Severe interactions can occur with co-administration of other antiarrhythmic agents, especially amiodarone. 

Antiarrhythmics

Lidocaine and Mexiletine (Class IB)

Side Effects

(6)

• The most frequent side effects are CNS including 
• tinnitus 
• seizures, 
• occasionally hallucinations, 
• drowsiness, 
• coma..

Antiarrhythmics

Quinidine (Class IA)

• Useful in treating supraventricular and ventricular arrhythmias, but there are significant risks of ventricular arrhythmias and other side effects.
• Torsades is likely to be the major cause of quinidine syncope, which occurs in as many as 5-10% of patients within the first few days of therapy.  
• Patients with a history of long QT, torsades, or hypokalemia should not be treated with quinidine. 
• *Patients with heart failure can have proarrhythmias and digoxin interactions. 
• *Quinidine is a potent inhibitor of hepatic CYP2D6 and is associated with more drug interactions than any other antiarrhythmic drug.

Antiarrhythmics

Quinidine (Class IA)

*Side Effects

(4)

• *Common side effects include; 
• hypotension, 
• GI problems (diarrhea and vomiting), 
• and cinchonism (tinnitus, blurred vision, and headaches). 

Antiarrhythmics

Procainamide (Class IA)

(7)

• Effective against both supraventricular and ventricular arrhythmias (including atrial arrhythmias associated with WPW syndrome); can be administered IV and orally. 
• Its major metabolite, N-acetylprocainamide (NAPA), has predominantly Class III antiarrhythmic actions.  
• Fast acetylators (~50% of the population) quickly convert procainamide to NAPA. 
• When procainamide is given orally, both procainamide and NAPA can contribute to the antiarrhythmic effects and toxicities; initial dosing should be conservative and monitoring of plasma concentrations is recommended. 
• Up to 40% of patients discontinue therapy within 6 months due to side effects
• Between 15 and 20% of patients develop a lupus-like syndrome, which usually begins as mild arthralgia, but can be fatal if allowed to progress. 
• These symptoms are reversed if therapy is stopped, but patients need to be warned of the early warning symptoms so therapy can be aborted before serious problems develop.

Antiarrhythmics

Disopyramide (Class IA)

(2)

Antiarrhythmics

Flecainide (Class IC)

(4)

• A potent fast inward sodium channel blocker used to treat symptomatic supraventricular arrhythmias and documented life-threatening ventricular arrhythmias. 
• Because of the risks of proarrhythmias identified in the CAST trials, the drug is not considered a first-line agent and should not be used in patients with impaired ventricular function, myocardial ischemia, or recurrent myocardial infarctions.
• The agent lowers ventricular function in most patients.  
• It also raises the threshold of pacing and cardiac defibrillators and should be used with caution in patients with pacemakers or ICDs.

Antiarrhythmics

Propafenone (Class IC)

(3)

• Used to treat symptomatic supraventricular arrhythmias and suppress life-threatening ventricular arrhythmias. 
• It is structurally similar to propranolol and has beta-blocking activity in addition to its sodium channel blocking activity.  
• At therapeutic concentrations it can have significant beta-blocking activity which must be considered in patients with heart failure.

Antiarrhythmics

Verapamil and Diltiazem (Class IV)

(6)

• Useful in treating a variety of arrhythmias of atrial or supraventricular origin. 
• More effective than digoxin in controlling ventricular rate in patients with atrial fibrillation 
• *High doses can cause AV block or suppression of SA node, particular when used in combination with beta-blockers, digoxin or other drugs that inhibit the SA and AV nodes
• *Should be used with caution in combination with drugs that inhibit SA and AV function, lower LV function, or lower blood pressure
• *The most common side effect of verapamil is constipation
• Grapefruit juice is known to increase the plasma concentrations of verapamil because it inhibits CYP3A4 in the gut wall

Antiarrhythmics

Verapamil and Diltiazem (Class IV)

Contraindicated in Pts W/

(7)

• heart failure, 
• impaired LV function, 
• sick sinus syndrome, 
• heart block, 
• severe hypotension or 
• reentrant arrhythmias due to Wolf-Parkinson-White (WPW) or Lown-Ganong-Levine (LGL) syndrome
• Administration of these agents to patients with atrial tachycardias resulting from WPW can worsen the arrhythmia by facilitating antegrade conduction through the ancillary tract leading to ventricular fibrillation

Antiarrhythmics

Dofetilide (Class III)

(5)

• The only Class III agent that is a relatively pure potassium channel blocker
• Used for the conversion and maintenance of normal sinus rhythm in highly symptomatic patients with atrial fibrillation or flutter
• Fewer non-cardiac toxicities than amiodarone and no negative inotropic effects
• Because of its effects on the potassium channel, it should not be used in combination with other drugs that prolong QT interval
• Because of the risks of torsades, ECG and renal function must be assessed prior to initiation of therapy; therapy must be initiated in a hospital setting by a trained prescriber

Antiarrhythmics

Ibutilide (Class III)

(3)

• This drug blocks outward potassium (IKr), but unlike other Class III agents, ibutilide also prolongs repolarization by increasing inward sodium flux through the slow inward sodium channels
• It is used IV to rapidly convert atrial arrhythmias to normal sinus rhythm; it is the only agent indicated for this purpose
• *Class IA or Class III drugs should not be used concurrently, or within 4 hours of ibutilide dosing, to avoid the possibility of DILQTS and torsades 

Antiarrhythmics

Ibutilide (Class III)

*Contraindicated in Pts w/

(4)

• prolonged QT, 
• torsades 
• or other polymorphic ventricular arrhythmias, 
• who are taking drugs that prolong QT or are associated with torsades

Antiarrhythmics

Sotalol (Class III and II)

(6)

• The racemic d,l mixture of sotalol has both Class II and Class III effects.  
• The l-isomer causes the beta-blocking effects, while the d-isomer causes the effects on prolonging the action potential. 
• The l-isomer causes significant beta-blocking effects at doses well below those required for the antiarrhythmic effects of the d-isomer. 
• The combination of Class II and III effects makes the drug effective in a variety of atrial and ventricular arrhythmias, though because of the proarrhythmic effects of Class III agents (torsades), high concentrations of the drug should only be used to treat life-threatening ventricular arrhythmias.
• Because of the risk of arrhythmia or MI, abrupt cessation of drug therapy should be avoided; instead gradually reduce dosage over a 1 to 2 week period or substitute a different beta-blocker.
• Drug combinations that enhance the pharmacological effects of sotalol (beta-blockade, QT prolongation, AV blockade) should be used with caution

Antiarrhythmics

Sotalol (Class III and II)

Contraindicated in Pts W/

(9)

• QT prolongation, 
• bradycardia, 
• torsades, 
• hypomagnesemia, 
• hypokalemia, 
• bronchospasm, 
• pulmonary edema, 
• heart failure, 
• or AV block.  

Antiarrhythmics

Amiodarone (ClassIII/Other)

(7)

• Though amiodarone is formally classified as a Class III antiarrhythmic, it has multiple actions and is more appropriately considered a "broad spectrum" antiarrhythmic
• Although it prolongs QT interval, its potential to cause proarrhythmias (torsades de pointes) is significantly lower than other Class III agents and it is one of the few antiarrhythmic agents to have consistently decreased mortality in many (but not all) clinical trials
• It is approved for use in refractory life-threatening ventricular arrhythmias, but its therapeutic role has been expanding to include a variety of arrhythmias ranging from supraventricular to ventricular
• Used IV, amiodarone is superior to lidocaine and other agents for the treatment of ventricular fibrillation (2000 ECC/AHA guidelines), and it is also used orally to suppress a variety of arrhythmias, even in combination with ICDs
• The safety of amiodarone for chronic therapy is controversial because of its variable and complex pharmacokinetics and many adverse effects, some of which can be fatal
• Without loading doses, it can take several weeks to months to achieve steady-state plasma levels.  Similar, it can take many months to clear the drug, with an elimination half-life ranging from 26 to 107 days (mean of 53 days)
• Amiodarone can interfere with the clearance of many drugs

Antiarrhythmics

Amiodarone (ClassIII/Other)

Most Common Serious Side Effects

(3)

• The most common serious adverse effects are;
•  pulmonary fibrosis and interstitial pneumonitis (2-15% of patients on chronic amiodarone), which is fatal in 10% of these patients.  
• The pneumonitis is reversible if drug is stopped early on, thus clinical assessment and chest x-rays are required every 3 months. 

Antiarrhythmics

Amiodarone (ClassIII/Other)

Other Adverse Effects

(6)

• GI disturbances
• hepatotoxicity (which can be fatal; 30% of patients have elevated serum liver enzymes)
• hyperthyroidism and hypothyroidism (2-24% incidence; amiodarone is structurally similar to thyroid hormone and contains large quantities of iodine)
• peripheral neuropathy (20-40% incidence, but reversible by lowering dose)
• dermatological reactions (15-20%) including photosensitivity (10%), which can result in blue-gray skin color, and various visual disturbances (10%)
• Virtually all patients on drug for more than 6 months develop corneal microdeposits which can eventually interfere with vision 

Antiarrhythmics

Dronedarone (Multaq)

(5)

• Dronedarone is a non-iodinated derivative of amiodarone approved in 2009 for use in non-permanent atrial fibrillation and flutter
• May be fewer adverse effects than amiodarone, but less effective in maintaining sinus rhythm
• Reduces morbidity and mortality in patients with high-risk paroxysmalandpersistent atrial fibrillation
• Dronedarone should not be given to patients with NYHA class IV heart failure or patients who have had an episode of decompensated heart failure in the past 4 weeks, especially if they have depressed ventricular function
• Can cause liver toxicity and interstitial lung disease

Antiarrhythmics

Dronedarone (Multaq)

Contraindications

(4)

• Permanent atrial fibrillation (patients in whom normal sinus rhythm will not or cannot be restored)
• Symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV symptoms
• Liver or lung toxicity, 
• hypersensitivity to drug 

Antiarrhythmics

Dronedarone (Multaq)

Adverse Reaction

(5)

• Liver injury, 
• worsening of heart failure, 
• pulmonary injury, 
• angioedema, 
• vasculitis

Antiarrhythmics

Dronedarone (Multaq)

Drug Interactions (many)

(6)

• Digoxin, 
• dabigtran, 
• warfarin, 
• beta-blockers, 
• calcium channel blockers, 
• drugs prolonging QT

Antiarrhythmics

Digoxin (Misc)

(6)

• Digoxin is a cardiac glycoside that acts by inhibiting the sodium/potassium ATPase.  
• This ion pump is ubiquitously expressed so digoxin affects a variety of excitable tissues including the heart, CNS and ANS. 
• Digoxin is used to control ventricular rate in patients with atrial tachycardias
• Digoxin increases vagal tone, thus inhibiting AV nodal conduction
• Digoxin can actually exacerbate atrial arrhythmias because it can cause calcium overload, but therapeutic efficacy is measured by the drug's ability to protect the ventricles by reducing the number of impulses passing through the AV node
• Digoxin has a relatively narrow therapeutic index and is known to interact pharmacokinetically with quinidine and other antiarrhythmic agents

Antiarrhythmics

Adenosine (Misc)

(9)

• Adenosine is an endogenous compound that is an agonist for purinergic (adenosine) receptors
• Activates outward K+ current in atrium, SA and AV nodes resulting in hyperpolarization
• It is given as a rapid IV bolus to acutely treat paroxysmal (reentrant) supraventricular tachycardia
• It potently blocks AV nodal conduction within 10-30 seconds of administration; also slows sinus rate
• It has a half-life of elimination of 1.5-10 seconds
• *Common side effects, which are short-lived, including 
• facial flushing, 
• dyspnea, and 
• chest pressure