Antiarrythmic Drugs

Panvilai Tangkulpanich 2nd Residency Emergency Medicine, Ramathibodi Hospital

Overview
Normal physiology of cardiac function Pathophysiology Drugs type and action Drug profiles

Normal sinus rhythm

Transmembrane potential electrical activity

A transmembrane electrical gradient (potential) is determined by the concentrations of the ff. ions: Sodium, Potassium, Calcium The movement of these ions produces currents that form the basis of the cardiac action potential

PHASES OF ACTION POTENTIAL

Phase 1 >Limited depolarization >Inactivation of fast Na+ channels Na+ ion conc equalizes > K+ efflux & Cl- influx

Phase 2 >Plateau Stage >Cell less permeable to Na+ >Ca++ influx through slow Ca++ channels >K+ begins to leave cell

Phase 3 >Rapid repolarization >Na+ gates closed >K+ efflux >Inactivation of slow Ca++ channels

Phase 0 >Rapid depolarization >Opening fast Na+ channels Na+ rushes in depolarization

Phase 4 >Resting Membrane Potential >High K+ efflux >Ca++ influx

Mechanisms of Cardiac Arrhythmias

Result from disorders of impulse formation, conduction, or both Causes of arrhythmias
Cardiac ischemia Excessive discharge or sensitivity to autonomic transmitters Exposure to toxic substances Unknown etiology

Mechanisms of Cardiac Arrhythmias

Altered automaticity
spontaneous phase 4 depolarization in nonpacemaker cells

Reentry
a common cause of narrow-complex tachydysrhythmias

Triggered (Afterdepolarization)

ANTIARRYTHMIC DRUGS

Classification

Classification

Classification

Case discussion(1)
65 year old woman with DCM, EF 10% Cardiac arrest and ROSC for 3 times maintenance with 3 inotropes EKG still Ventricular tachycardia and Fibrillation after Amiodarone maximum dose

Case discussion(1)
Which drugs can help?

CLASS I: Sodium Channel Blocking Drugs

Subclass
Example Na Blockage (phase 0) AP duration and Repolariztion

A
Procainamide Quinidine Moderate Prolong

B
Lidocain Phenytoin Minimal Shortening

C
Propafenone Slow Prolong

CLASS I: Sodium Channel Blocking Drugs

CLASS I: Sodium Channel Blocking Drugs

IA : Procainamide
treat both atrial and ventricular arrhythmias, increases refractory period, Depress myocardium activity, anti-choilnergic effect

Indication
Refractory wide-complex tachycardia with good LV function

Adverse effect
Drug in duce SLE, Bone marrow suppression, Negative inotropic effect

CLASS I: Sodium Channel Blocking Drugs

IB : Lidocain
Effective in ischemic tissue, no negative inotropic

Indication
Vfib, digitalis-associated arrhythmias

Adverse effect
CNS depression (plasma level > 5 mg/ml)

Dose
1-1.5 mg/kg load Decrease dose 50% in eldery, CHF, Liver disease

CLASS I: Sodium Channel Blocking Drugs

IC : Propafenone Derivative of Propanol Dont have in Thailand

Case discussion(2)
Young woman with known case thyrotoxicosis came to ER with HR 150/min with agitation

Case discussion(2)
Which drugs can help?

Class II adrenergic blockers

Effective in atrial & ventricular arrhythmias that associated with increase in sympathetic activity
Increase AV nodal conduction
Useful in terminating reentrant arrhythmias that involve the AV node & in controlling ventricular response in AF & A.fib.

Increase PR interval Prolong AV refractoriness Reduce adrenergic activity

Class II adrenergic blockers

Esmolol
Short acting, selective BB 2nd line drug in SVT, AF from MI No renal adjustment

Propanolol
Used for supraventricular arrythmia eg. MAT, AF with good LV fn, Tachycardia from thyrotoxicosis

Case discussion(3)
Old man with chest pain, BP 180/90 mmHg, PR 160/min

Case discussion(3)
Which drugs can help?

CLASS III: Potassium Channel Blockers

Drugs that prolong effective refractory period by prolonging action potential Prolong AP by blocking K+ channels in cardiac muscle ( inward current through Na+ & Ca++ channels

CLASS III: Potassium Channel Blockers

Amiodarone
Most tachyarrhythmias (AF, VF, VT, WPW) OK if impaired LV function Rate control and converts rhythm Cardiac arrest: 300 mg IV push (max 2.2g/24hrs) Stable VT: 150 mg IV repeat 10 min or infusion 360 mg IV over 6 hrs (1mg/min) Maintenance infusion: 540 mg over 18 hrs (0.5mg/min)

CLASS III: Potassium Channel Blockers

Amiodarone : Adverse effect
Gray- blue skin discoloration & photodermatitis . Corneal microdeposits corneal opacity ,optic neuritis, blindness pulmonary fibrosis hypo or hyperthyroidism Nausea & constipation Hepatic impairment neurological effects

CLASS III: Potassium Channel Blockers

Amiodarone
Eliminated by liver mostly as active metabolites. No renal adjustment Caution for hypotensive patient

Case discussion(4)
Young man, walk in with palpitation, HR 180/min

Case discussion(4)
Which drugs can help?

Class IV Ca2+ channel blockers

slow rate of AV-conduction in patients with atrial fibrillation Main site of action on SA node and AV node Affective in only atrial arrythmia Alternative drug for SVT Not effective in WPW

Class IV Ca2+ channel blockers

Verapamil and Diltiazem Indication
PSVT, AF

Contraindication
WPW

Dose
Diltiazem : 0.25 mg/kg q 15 min Verapamil : 5-10 mg IV (decrease 50% in elderly and impair liver function)

Miscellaneous drugs
Adenosine Digitalis Magnesium

Miscellaneous drugs : Adenosine

Binds to specific G protein coupled adenosine receptors (A1&A2)opening K+ channel hyperpolarization. Interrupts re-entry and aberrant pathways through AVN Drug for narrow complex PSVT

Miscellaneous drugs : Adenosine

Contraindications:
VT Hypotension and deterioration High degree AV block Poison or drug induced tachycardia Bronchospasm but short acting

Miscellaneous drugs : Digitalis

Indirectly alters autonomic outflow by increasing parasympathetic tone & decreasing sympathetic tone Results in decreased conduction time & increased refractory period in the AV node reduce ventricular response to supraventricular arrythmia Inotropic: Increases force of contraction Negative chronotrope: Slows HR

Digoxin
Na+-K+ATPase inhibition Direct AV nodal suppression
increase automaticity Delayed afterdepolarization Increase AVnode refractory period

Parasympathetic Slow AV conduction effect Decrease SA node firing

 efficiency of Na+/Ca antiporter: intrecellular Ca:

Miscellaneous drugs : Digitalis

Contraindications:
WPW. SSS.

Elderly or renal failure reduce dose or TOXICITY

0.25 to 0.5 mg IV; then 0.25 mg IV every 4 to 6 hours to maximum of 1 mg Onset 0.5-1 hr, duration 2-4 hr

Miscellaneous drugs :

2+ Mg

Effective in patients with recurrent episodes of torsades de pointes (MgSO4 1 to 2 g IV) & in digitalisinduced arrhythmia Mechanism Of Action
unknown influence Na+/K+ ATPase, Na+ channels, certain K+ and Ca++ channels

Case discussion

Bidirectional VT from Digitalis intoxication

Case discussion

Case discussion
Which drug?

Answer
Pt with BP 70/50 Dont use any drug, should do cardioversion Treat the patient, Do not treat EKG!

Take home massage

Mechanism of antiarrythmic drugs are from mechanism of action potential of heart Every Antiarrythmic drugs are proarrythmic agents Treat the Patient with knowledge you know