anti-arrhythmic drugs cardiac arrhythmias are commonly seen during myocardial ischemia, digoxin...
TRANSCRIPT
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
Anti-arrhythmic drugs
Anti-arrhythmic 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
Anti-arrhythmic drugs
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
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
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)
Anti-arrhythmic drugs
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
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
Anti-arrhythmic drugs
CLASS IA : Quinidine : Adverse effects :
• GIT : Diarrhea, nausea, vomiting and cinchonism – ringing in ears.
• Precipitate torsades de pointes by prolonging QT interval
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
• CLASS II : Beta blockers : Propranolol, Metoprolol, Carvedilol• CLASS III : Agents widening APD :
K channel blockers : Amiodarone, Sotalol, Ibutilide• CLASS IV : CCB : Verapamil, Diltiazem
Anti-arrhythmic drugs
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
Anti-arrhythmic drugs
BETA BLOCKERS
Anti-arrhythmic drugs
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
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
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.
Anti-arrhythmic drugs
Anti-arrhythmic drugs
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
Anti-arrhythmic drugs
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
Anti-arrhythmic drugs