DRUGS FOR ARRHYTHYMIAS ^^

ARRHYTHYMIA

• Greek word: “a” – absence + “rhutmos” – lack of • Torsades de Pointes

rhythm ↑ ↓ → ←
• most common cause of death in patients with a
myocardial infarction or terminal heart failure
• Also called as “Dysrhythmias” ← disturbed
• any cardiac rhythm that is not normal sinus rhythm
• perturbation of the normal sequence of impulse
initiation and propagation
• Major causes:
- abnormal automaticity ← involuntary
- a ventricular arrhythmia of great pharmacologic
importance because it is often induced by
antiarrhythmic and other drugs that change the shape
of the action potential and prolong the QT interval.
ELECTRO-PHYSIOLOGY OF CARDIAC RHYTHM
• The electrical impulse that triggers a normal cardiac
contraction originates at regular intervals in the
sinoatrial (SA) node.
• This impulse spreads rapidly through the atria and
enters the atrioventricular (AV) node,

- abnormal conduction • The impulse then propagates over the His

• Sinus Tachycardia ← over 100 bpm: S/sx: palpitations, -Purkinje system and invades all parts of the ventricles.
syncope, cardiac arrest
• Contraction of all the ventricular muscle is normally
• Sinus Bradycardia ← less 60 bpm: Asymptomatic synchronous and hemodynamically effective.

• SINO ATRIAL (SA) NODE → ATRIOVENTRICULAR (AV) ACTION POTENTIAL PHASE

NODE → PURKIJE FIBERS (network in heart)
0 – UPSTROKE – influx of sodium ions
NATURE OF ARRHYTHYMIAS
1 – EARLY FAST – termination of sodium ion influx
• Atrial Fibrillation
2 – PLATEAU – influx of calcium ion
- most common serious arrhythmia and, as noted above,
3 – REPOARIZATION – influx of potassium ions
is particularly common in older patients
4 – DIASTOLE – resting membrane potential
- often symptomatic and may contribute to worsening
heart failure

• Ventricular Tachycardia

- A very common arrhythmia, often associated with

myocardial infarction; ventricular tachycardia may
involve abnormal automaticity or abnormal conduction,
usually impairs cardiac output, and may deteriorate into
ventricular fibrillation; for these reasons it requires
prompt management.

• Supraventricular Tachycardia

- A reentrant arrhythmia that travels through the AV

node; it may also be conducted through atrial tissue as
part of the reentrant circuit. ELECTROCARDIOGRAM
DRUGS FOR ARRHYTHYMIAS ^^
• ECG – body surface manifestation of the IV – Ca2+ Channel Blockers
depolarization and repolarization waves of the heart

• P wave is generated by atrial depolarization

• QRS by ventricular muscle depolarization

• T wave by ventricular repolarization

• PR interval is a measure of conduction time from

atrium to ventricle

• QRS duration indicates the time required for all of the

ventricular cells to be activated.

• QT interval reflects the duration of the ventricular

action potential

PRETREATMENT EVALUATION CLASS 1A SODIUM CHANNEL BLOCKERS (DQP)

- Eliminate the cause PROCAINAMIDE (Pronestyl®)

• Precipitating factors • can be used in all types of arrhythmias

- Make a firm diagnosis Effects:

• Arrhythmia diagnosis • slows conduction velocity and pacemaker rate

- Determine baseline condition • prolongs action potential duration

• Underlying heart condition • direct depressant effects on SA and AV nodes

- Question the need for therapy S/E: systemic lupus erythematosus, hypotension

• Cardiac Arrhythmia Suppression Tool QUINIDINE (Cardioquin)

ANTIARRHYTHMIC DRUGS - Cinchona bark

Goals: • Sulfate [83%], Gluconate [62%], Polygalacturonate

[60%] (Cardioquin®)
- Na+ channel blockade
Effects:
- Inhibition of sympathetic innervation
• slows the upstroke of the action potential
- Prolong refractory period
• slows conduction
- Ca2+ channel blockade
• prolongs the QRS duration of the ECG
CLASSIFICATION
A/E: Cinchonism (tinnitus, HA, dizziness)
Vaughan-Williams-Singh
DISOPYRAMIDE (Norpace®)
- Miles Vaughan-Williams & Bramah Singh
• not used as a first-line antiarrhythmic agent
I – Na+ Channel Blockers
USE: treatment of ventricular arrhythmias
II – β Blockers
S/E: anticholinergic
III – K+ Channel Blockers
DRUGS FOR ARRHYTHYMIAS ^^
CI: pts w/ HF • Acebutolol (Sectral®)

• Sotalol (Betapace)

CLASS 1B SODIUM CHANNEL BLOCKERS (TMLP)

LIDOCAINE (Xylocaine) – IV USES:

• Least cardiotoxic • Esmolol, a very short-acting β blocker (IV) – acute

USE: mgmt. of Digoxin-induced ventricular tachycardia
MEXILETINE (Mexitil®)
• orally active congener of lidocaine
arrhythmias.
• Propranolol, Metoprolol, Timolol – used chronically
to prevent arrhythmias in patients who have had a
myocardial infarction

USE: treatment of ventricular arrhythmias EFFECTS:

TOCAINIDE (Tonocard®) • Direct membrane effects (sodium channel block) and

• oral, suppress the s/sx of VT
PHENYTOIN (Dilantin®)
• oral, IV, arrhythmias associated w/ digitalis toxicity
CLASS 1C SODIUM CHANNEL BLOCKERS (MFPE)
FLECAINIDE (Tambocor®)
- potent blocker of sodium and potassium channels
PROPAFENONE (Rythmol®)
- possesses weak β-blocking activity
prolongation of action potential duration
• slows SA node automaticity and AV nodal conduction
velocity
CLASS 3 POTASSIUM CHANNEL BLOCKERS
AMIODARONE (Cordarone) - (PO, IV)
• Contains 32% Iodine
USE: 1st line mgmt. of ventricular tachycardia
S/E: hepatotoxicity, pulmonary fibrosis, WolffChaikoff
effects

A/E: metallic taste, constipation EFFECTS: prolongs action potential duration and QT
interval; slows heart rate and AV node conduction; low
ENCAINIDE incidence of Torsades de Pointes
• withdrawn from the US market DRONEDARONE (Multac) - (PO)
• aggravate arrhythmia • Analog which is devoid of Iodine content
MORICIZINE VERNAKALANT
• phenothiazine derivative • Investigational drug for the treatment of atrial
• withdrawn from the US market fibrillation
• prolongs the atrial effective refractory period and
slows conduction over the AV node
CLASS 2 BETA BLOCKERS A/E: dysgeusia, sneezing, paresthesia, cough,
hypotension
• Metoprolol (Lopressor®)
SOTALOL (Betapace)
• Propranolol (Inderal®)

• Esmolol (Brevibloc®)
DRUGS FOR ARRHYTHYMIAS ^^
• has both β-adrenergic receptorblocking and action • Poorly understood
potentialprolonging actions
• interacts with Na+/K+- ATPase, K+, and Ca2+ channels
• well absorbed orally with bioavailability of
approximately 100% USE: Torsades de Pointes

DOFETILIDE (Tikosyn)

USE: maintenance of normal sinus rhythm in patients POTASSIUM

with atrial fibrillation
USES:
IBUTILIDE (Corvert)
• Digitalis-induced arrhythmias
• more effective in atrial flutter
• arrhythmias associated with hypokalemia
A/E: Torsades de Pointes
EFFECTS:

• Slows ectopic pacemakers

CLASS 4 CALCIUM CHANNEL BLOCKERS
• Slows conduction velocity in heart
VERAPAMIL (Isoptin)
DIGOXIN
• Most efficacious CCB for arrhythmia
USE: mgmt. of atrial fibrillation
EFFECTS: AV conduction velocity is decreased, and
effective refractory period and PR interval are increased ➢ Narrow therapeutic index
➢ Potassium monitoring
USE: mgmt. of chronic paroxysmal supraventricular
tachycardia EFFECTS:
S/E: constipation • Hyperpolarization
DILTIAZEM (Cardizem) • shortening of atrial action potentials
• appears to be similar in efficacy to verapamil in the • increases in AV nodal refractoriness
management of supraventricular arrhythmias

CLASS 5 MISCELLANEOUS NON-PHARMACOLOGIC THERAPY

ADENOSINE (Adenocard) 1. External defibrillation

• IV bolus 2. Implanted defibrillators

• Short duration
3. Implanted pacemakers
USE: mgmt. of PSVT
4. Radiofrequency ablation / Cryoablation
S/E: bronchoconstriction
of arrhythmogenic foci via catheter
MOA: induce potassium efflux, induce calcium influx →
prevent firing of new action potentials

MAGNESIUM

• Magnesium sulfate (MgSO4)

• IV infusion

MOA: