Arrhythmias can cause it

Leading cause of death in the US: 450,000/year

CAD is the biggest risk factor, smoking is the most common cause of CAD

A-Fib: Disease of aging; <1% of <60, 10% of >80

Treatment of arrhythmia: Drug therapy, electrical therapy, defibrilation (given at any time in v-fib, coordinated at the same time as R wave in A-fib, atrial flutter, supraventricular tachycardias (called cardioversion))

Accessory pathway: Provides excess stimulation to a specific area of the heart, resulting in arrhythmia->accessory pathway is identified via electrophysiology study (EPS) and ablated with a laser->95% cure rate

Brady arrhythmias: Pacemaker can be implanted

Long term care of patients that survive SCD: Defibrilator implanted

A-Fib: MAZE procedure can be used

Vaughan Williams Classification System:

Class I: Sodium channel Blockers: Decrease phase 0 slope and peak of AP

Class IA: Moderate NaChB: Moderate decrease in phase 0-> Increased action potential duration (APD) and effective refractory period (ERP)

Class 1B: Weak NaChB: Small decrease in phase 0-> Decreased APD and ERP

Class IC: Potent NaChB: Large decrease in phase 0->No effect on APD or ERP

Class II: Beta Blockers: Block sympathetic activity->Decrease HR and conduction

Class III: Potassium Channel Blockers: Delay repolarization (phase 3)->Increase APD and ERP and prolong QT

Class IV: Calcium Channel Blockers: Block L-type Ca channels->Decrase HR and conduction, most effective in SA and AV nodes

Older drugs with many SE's including torsades

Moderate NaChB's, decrease slope during phase 0 to increase ERP and ADP

Quinidine: No longer used but compared to other drugs in trials; Maintains sinus rhythm in atrial firbrilation or flutter;

SE: Acts as an alpha-blocker to inhibit vagus->Hypotension, sinus tachycardia, atrial tachycardias; pro-arrhythmia effects in a non-dose-related fashion (lower the dose won't help); Diarrhea

Disopyramide: Anticholinergic->Glaucoma, constipation, dry mouth, urinary retention; Negative inotrope (decreases contractility); Only use=hypertrophic cardiomyopathy b/c disopyramide reduces stiffness; Liver and kidney metabolism

Procainamide: Similar to quinidine, but no vagus inhibition; Also has KChB activity; Go-to drug: treats pupraventricular and ventricular arrhythmias, safe in pregnancy; Active metabolite=NAPA, which has KChB activity but no NaChB activity (acts like class III)

SE: Lupus-like syndrome-Almost all develop positive ANA titer but only 15-20% experience symtpoms

Weak NaChB, mildly decreases phase 0 slope to decrease ADP and ERP

Lidocaine: Local anesthetic; treats ventricular arrhythmias; big 1st pass metabolism->oral therapy ineffective

SE: Neurologic symptoms: Altered consciousness, tremors, dysarthria, nystagmus, seizures

Does not improve long term survival, so amiodarone is now preferred for ventricular arrhythmia

Potent NaChB's, produce a large decrease in slope of phase 0 but don't efect ADP or ERP

Use dependence: dissociate slowly from Na+ channels during diastole, so they're more effective at rapid heart rates (class III drugs have reverse use-dependence); Cause some pro-arrhythmic activity->ventricular tachycardia

Also have KChB activity->Could increase APD in ventricular myocytes

Flecainide: Prolongs PR, QRS, and QT intervals; Treat atrial arrhythmias; only available orally; 25% eliminated by kidneys, 75% by liver; Negative inotrope (don't give in HF)

SE: Can accelerate ventricular rate in patients with atrial flutter because the drug slows conduction of atria but doesn't alter AV nodal conduction->B-Blocker should be given before flecainide to prevent V-Tach

Other SE's: Re-entrant V-Tach, Increased mortality in patients w/ previous MI or abnormalities in cardiac structure (this effect was found by CAST study)

Propafenone: Oral; Given for supraventricular tachycardias; Has B-Blocker activity->can't give w/ asthma, COPS, bradycardia; Excreted hepatically and renally

Cadioprotective-decrease SCD, reduce mortality in patients with previous MI

Decrease intracellular Ca overload, inhibit after-depolarizaiton-mediated automaticity; Increase energy required to fibrilate the heart

Slows conduction in SA and AV nodes and accessory pathways->prevent re-entry arrhythmias and atrial arrhythmias

SE: Fatigue, depression, impotence, bronchospasm

Must be given for: CAD, MI, Heart surgery

Don't give with: bradyarrhythmias, asthma, COPD

Must be tapered rather than stopped abruptly so no rebound effect doesn't happen

Sotalol: Non-Selective B-Blocker; treats V-Tach, A-Fib, A-Flutter; Excreted by kidneys

SE: EAD's (early after depolarizations), bronchospasms

Esmolol: B1 selective; Short t1/2, given by IV, used in ICU

Block K channels to prolong repolarization and prolong APD and ERP->prolonged QT and increased torsades risk

QTc (corrected): Shouldn't be >440msec in men, 450msec in women; May be nearly 600 with class III's

Pro-arrhythmic, Dose dependent Torsades (least likely to be caused by amiodarone)

Reverse-use dependent: More effective the less the K+ channel is being used (proarrhythmic at low HR's)

Dofetilide: Orally to convert A-fib or A-flutter to sinus rhythm or to maintain sinus rhythm after cardioversion

SE: Torsades, Renal

Don't give in: Patients with long QT; Patients taking verapamil, cimetidine, trimethoprin, ketoconazole, hydrochlorothiazide

Ibutilite: Only FDA drug for treating acute A-Fib; Cleared hepatically

Sotalol: Mixed class; Nonselective B-Blocker in addition to KChB; Ventricular and Supraventricular arrhythmias; Renally cleared

Amiodarone: Looks like thyroid hormone; very lipophilic; Cleared hepatically; Bioavailability of 30%; t1/2=weeks to months; Indicated for acute V-Tach/Fib

SE's: Profound inhibitor of liver metabolism->many drug interactions; Very toxic to every system but GI: turn blue, eye deposits, AV block, cirrhosis, thyroid distrubance, lowers lung diffusion capacity; glove and stocking peripheral neuropathy

Dronedarone: Amiodarone derivative w/o iodine, less lipophilic, and metabolized by only 1 CYP-CYP3A4 (less SE's); Indicatd for A-Fib/Flutter

Bad: Increases mortality, hepatotoxic

Non-DHP's: Verapamil (best antiarrhythmic) and Diltiazem

Arterial dialators that also affect L-type Ca channel in SA and AV node->Prolongs conduction from atria to ventricles

Don't reduce mortality like B-Blocker->Only give when B-Blocker is contraindicated

Increases intracellular Ca->positive inotrope and decreaed conduction through AV node

Use for: Bed-Ridden patients (b/c sympathetics can override digoxin in physical activity)

Don't give in: Patients with excessive SNS stimulation (lung disese, hyperthyroidism)

75% bioavailable, slow onset of action

Serum levels do not predict toxicity

Toxicity: See yellow, altered mental status, fatigues, GI upset

Risk for toxicity: Renal insufficiency, cardiac disease, metabolic disturbances

A lot of drugs interfere with it; Only rifampin decreases digoxin levels

Can cause delayed afterdepolorization (DAD)->A tach or AV block

Anti-digozxin: paradoxically increases serum drug levels

Slows both sinus rate and AV node conduction by blocking Ca currents

Use for: Paroxysmal (sudden) supraventricular tachycardia or PSVT; diagnostically to reveal flutter in EKG or use as vasodilator in stress test

Blocked by: Methylxanthines like theophylline and caffeine; potentiated by dypiramidole and heart transplant

SE: asystole, chest pain, hypotention, bradycardia

SA and AV nodes are slow and based on Ca+

Phase 0: Depolarization from inward Ca (slow) or Na (fast)

Phase 1: Rapid repolarization from outward K+

Phase 2: Plateau from Inward Ca and Outward K through delayed rectifier channels; Effective refractory period

Phasse 3: Repolarization from Closing of Ca and continued outward K

Phase 4: Restoring of resting membrane potential by Na, Ca, an K; Automaticity-Controls HR

SNS allows more Na and K to enter SA during diastole->Increases automaticity and HR

SNS allows Ca to enter AV node more quickly->Increases speed of conduction