Anti-arrhythmic drugs Cardiac arrhythmias are commonly seen during myocardial ischemia, digoxin...

Anti-arrhythmic drugs

• Cardiac arrhythmias are commonly seen during myocardial ischemia, digoxin treatment and anesthesia.

• Anti-arrhythmic drugs are used to prevent and treat cardiac arrhythmias.To treat

bradyarrhythmias

Atropine and Isoproterenol (pacemaker)

To treat tachyarrhythmias

Antiarrhythmic drugs


• The electrical impulse that triggers cardiac contraction originates in SA node and travels through atria and AV node and then propagates over purkinje system and invades all parts of ventricles.

• Arrhythmias are caused by 1. Abnormalities in the generation or2. Abnormalities in the conduction of

the electrical impulses or3. Both.

Normal Atrial fibrillation


The following are the causes of arrhythmia

• Abnormal generation of impulse

o Enhanced / ectopic pacemaker activityo After-depolarization• Abnormal impulse conductiono Re-entryo Conduction block


Abnormal generation of impulse :• Enhanced automaticity : beta receptor

stimulation

• Atrial and ventricular cells may have pacemaker activity in hypokalemic conditions.

• After-depolarization is of two types -- 1. Early After Depolarization that occur during late phase 2 or phase 3 as in bradycardia or 2. Delayed After Depolarization that occur during phase 4 when intracellular load is high (digoxin toxicity).

Abnormal conduction of impulse : Re-entry

• There has to be an obstacle to homogenous conduction (anatomic or physiological).

• Normally electrical excitation becomes extinguished at the end of the circuit due to collision of impulse.

• An unidirectional block prevents anterograde impulse but retrograde impulse is propagated.



Class I Mechanism of action Examples Comments

Ia Na channel blockers that ↑ APD

Quinidine Procainamide

Large block OPEN Na & K Channels, hence both QRS & QT affected.

Ib Na channel blockers that may slightly ↓ APD

Lidocaine Mexiletine Phenytoin

High affinity for INACTIVATED than open Na channels with rapid unbinding during diastole, hence little effect on QRS; also blocks the small Na plateau current which may slightly shortens the APD.

Ic Na channel blockers that do not change APD

Propafenone Flecainide

Large block of OPEN Na channels & very slow unbinding during diastole markedly prolong QRS.


Class I : Sodium channel blockers: – State dependent blocking action

(high affinity for open/inactivated channel) causes

effective refractory period (ERP).– Rate dependent blocking action

(greatest at fast heart rates)


CLASS IA : Quinidine • Cinchona bark, dextro isomer of

quinine.• It blocks the sodium channel and

also potassium channel.• It has anti-muscarinic (decrease the AV

node refractory period, which can result in a rapid acceleration of ventricular rate) and alpha blocking action.


CLASS IA : Quinidine • It is bitter and irritant.• Quinidine is also an inhibitor of the

cytochrome P450 type 2D6.• It ↑↑ plasma digoxin by displacing it from

tissue binding sites and decreasing its excretion.

• Used (rarely because of proarrhythmic effects) in the treatment of supraventricular tachycardia (after AV block) and ventricular tachycardia


CLASS IA : Quinidine : Adverse effects :

• GIT : Diarrhea, nausea, vomiting and cinchonism – ringing in ears.

• Precipitate torsades de pointes by prolonging QT interval


Class IA : Procainamide • Used for the treatment of

ventricular tachycardia (second/third choice after amiodarone & lidocaine).

• Chronic use result in a positive anti-nuclear antibody (ANA) titer and SLE like syndrome (arthralgia and arthritis) especially in slow acetylators.


Class IA : Procainamide • Procainamide is converted to N-

acetylprocainamide (NAPA), which blocks potassium channels (prolongs APD, but does not block Na channels).

• NAPA accumulation has been implicated in producing torsade de pointes in patients with renal failure.


CLASS IB : Lidocaine: Least cardiotoxic :• Block Na channels: preference for

INACTIVATED channels in partially depolarized cells of ischemic area.

• High first pass metabolism – not given orally

• Used in treatment of ventricular arrhythmia and also in digoxin induced arrhythmias.

• Main toxicity is neurological – drowsiness, confusion and nystagmus.


CLASS IC : Flecainide• This is a class of potent Na channel

blocker • Drugs of this class have negative inotropic

effect and highly pro-arrhythmogenic especially in setting of myocardial infarction.

• Flecainide is indicated for life threatening ventricular fibrillation and refractory or symptomatic supraventricular arrhythmia.


• CLASS II : Beta blockers : Propranolol, Metoprolol, Carvedilol• CLASS III : Agents widening APD :

K channel blockers : Amiodarone, Sotalol, Ibutilide• CLASS IV : CCB : Verapamil, Diltiazem


CLASS II : BETA BLOCKERS :• Propranolol, Metoprolol, Esmolol,

Carvedilol• These diminish phase 4 depolarization –

decreasing automaticity• Prolong AV conduction• Prevent re-infarction & sudden death in

patients with a history of CHF or MI• Used for the control of ventricular rate in

patients with atrial fibrillation


BETA BLOCKERS


CLASS III : POTASSIUM CHANNELBLOCKERS : Amiodarone• It is an iodine containing highly

lipophilic anti-arrhythmic with multiple actions

o Block K channels o Block inactivated Na + channelso Inhibit Ca channels


Class III : Amiodarone :• Used in wide range of ventricular and atrial

arrhythmia.Adverse effects : • Pulmonary fibrosis, Hepatotoxicity• Skin pigmentation, Corneal deposits

• Thyroid abnormalities – hypothyroidism

(common)

• Amiodarone inhibits CYP 450 & can cause drug interactions.

Pigmentation Related to Amiodarone

Clinical indications of Amiodarone:

Acute suppression of post-MI ventricular arrhythmias in the Coronary Care Unit

Preferred drug to maintain normal sinus rhythm in patients with atrial fibrillation (rhythm control)

Other Class III : K channel blockers • Sotalol : Treatment of ventricular and

atrial arrhythmia but needs monitoring. • Dofetilide and Ibutilide : Treatment

of atrial flutter and fibrillation• Torsades de pointes is the most

serious side effect of this K channel blockers.


Class IV : Calcium channel blockers: Verapamil and Diltiazem

• These are used in the treatment of PSVT (supraventricular tachycardia) next to adenosine.

• These are used to control the ventricular rate in chronic atrial fibrillation.

• Used in angina and prophylaxis of migraine. • They reduce the contractility of the heart,

so not appropriate to use in heart failure.



Adenosine : Drug of choice for PSVT

• It activates the K channels in the AV node. – hyper polarization;

• AV conduction is slowed.• Short half life ~ 10 s• Terminates the paroxysmal

supraventricular tachycardia (PSVT) • Bronchospasm is the major adverse

effect


Adenosine :

Conclusions :• Atrial flutter and fibrillation can be

treated by class III antiarrhythmic agents.

• Supraventricular tachycardia is treated by adenosine, CCB and beta blockers.

• Ventricular arrhythmias are usually treated by amiodarone / lidocaine.


Anti-arrhythmic drugs Cardiac arrhythmias are commonly seen during myocardial ischemia, digoxin...

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