drug induced arrhythmia dr. sh tsui 15 june 2005

Drug Induced Arrhythmia

Dr. SH TSUI

15 June 2005

ECG Disturbances in Poisoned Patients Fast rate Slow rate Abnormal rhythm/pattern

Focus: Underlying mechanism and patho-physiology

Cardiovascular Physiology

Electrolyte movement and action potential

Action potential of different cardiac muscle cells

Normal Depolarization

Normal Repolarization

Cardiovascular Toxicity

Mediated by affecting: Calcium channel Sodium channel Potassium channel Na-K-ATPase Pump Electrolyte disturbances Autonomic nervous system

Adrenergic receptors

1 Heart HR, Ionotropy

SA/AV conduction

2 Heart HR(?), Ionotropy

Arterioles Relaxation

1 Arterioles Vasoconstriction

2 CNS SYM outflow

Drug Induced Tachycardia 1

Enhanced SYM tone1. Response to increases substrate requirement Tissue hypoxia

Hypoglycaemia Increased centrally mediated psychomotor

activity All stimulants

Salicylates CO

Drug Induced Tachycardia 1

Enhanced SYM tone

2. SYM stimulation Direct central activation

Direct peripheral

Cocaine Amphetamine

Theophylline

Withdrawal

Drug Induced Tachycardia 2

Reflexive Response Response to contractility Response to vasodilatation Response to hypovolaemia

Salicylates

TCA

Drug Induced Tachycardia 3

Parasympathetic antagonism Antagonism of Ach receptors on the

myocardium Release of Ach from the nerve

terminal

Drug Induced Tachycardia 4

Enhanced myocardial sensitization

sensitivity to catecholamines Predispose to tachycardia and

arrhthymia

HalogenatedHydrocarbon

Mnemonics

F: A:

S: T:

Free base or other forms of cocaine

Anticholinergics, Antihistamines, Amphetamines, Antipsychotics

Sympathomimetics, Solvent abuse

Theophylline

Drug Induced Bradycardia 1

Altered autonomic tone

Enhanced cholinergic tone

1. Increased central PARA tone

2. Cholinesterase inhibition

Central

Myocardial muscarinic Ach receptors

Organophosphates

Drug Induced Bradycardia 1

Altered autonomic tone Altered SYM tone

1.

2. Clonidine/Imidazolines

3. Depletion of circulating catecholamines

Sedative-hypnotic

Central α2 agonism SYM output

Drug Induced Bradycardia 1

Reflex response Baroreceptor reflex response to HT

PPA

Drug Induced Bradycardia 2

Toxicity on conduction and pacemakers Mediated by affecting:

1. Na/K ATPase pump

2. Sodium channel

3. ß1 Adrenergic receptor

4. Potassium channel

5. Calcium channel

Calcium Channel Blockers Inhibits SA and AV nodal conduction resulting

in bradycardia and heart block

CCB Toxicity: Treatments

Atropine Calcium Catecholamines Insulin Glucagon Phosphodiesterase

inhibitor

ß Blockers Toxicity

Decrease SA node function Impaired AV conduction Prolonged QRS (Membrane stabilizing

activities) Prolonged QT intervals (K channel

Blockade)

ß Blockers Toxicity: Treatment

Atropine Glucagon Calcium Insulin Catecholamines Phosphodiesterase

inhibitor

Mnemonics

P: A: C: E: D:

Propranolol(ß-blockers), Poppies

Anticholinesterase, Aconitine

Clonidine, CCB, Ciguatera

Ethanol or other alcohols

Digoxin

Arrhythmia

Underlying mechanisms Increased automaticity Re-entry Triggered automaticity

1. Delayed after depolarization

2. Early after depolarization

Automaticity: Digoxin

Excessive elevation of the intracellular calcium elevates the resting potential

Producing increased automaticity

Re-entry: Anti-dysrhythmic agents

TCA

Terminal right axis deviation

RBB is preferentially affected

Appearance of right ventricular force at the late phase of QRS

Predictive Values

QRS duration Seizures: 0% if <100ms, 30% if >100ms Ventricular dysrhythmias:

0% if <160ms, 50% if >160ms

Boehnert M, N Eng J Med 1985 313;474-479

Predictive Values

Amplitude of terminal R wave in aVR:

RaVR 3mm predicts seizures and dysrhythmia

Liebelt EL Ann Emerg Med 1995;26:195-201 Terminal R-axis deviation, prolonged

QTc, sinus tachycardia: specific and sensitive for TCA OD

Wolfe TR Ann Emerg Med 1989;18:348-351

TCA: tachyarrhythmia

VT Mechanisms Non-uniform conduction slowing

Re-entry Precipitated by hypoxia, tissue

ischaemia and metabolic acidosis

Sinus tachycardia plus aberrancy is more common

Delayed After-depolarization

Normal depolarization is followed by an oscillation during phase 4

Occurs with intracellular Ca E.g. Cardiac glycoside toxicity

Digoxin Toxicity: Risks of treatment Pacing: DAD amplitude Overdrive supression: Useless in

dysrhythmias due to automaticity DC version: Risk of inducing VF/VT Treatment choices: Atropine,

Lignocaine, Phenytoin, Amiodarone

*Digoxin antibody

Early After-depolarization

Occurs during the downslope of phase 3 of the action potential

Occurs when cardiac action potential is markedly prolonged ( QTc)

Drugs that cause QT prolongation

Aconitine Toxicity

Na influx through Na channel Delay the final phase of repolarization

and promote premature excitation Expect Na channel blockers to be

effective Amiodarone, flecainide, procainamide

have been reported to be successful in terminating ventricular dysrhthymias

Treatment of Drug-induced ventricular dysrhythmias NaHCO3 if widened QRS Lignocaine for prolonged QT Mg, DC version, Overdrive pacing for

Torsades de pointes, correct e-

Toxin Induced SVT

Usually mediated by sympathomimetic activity of drugs

Cardioversion Adenosine: may not be effective for

methylxanthines toxicity CCB and ß-blockers: risks Toxin removal

Conclusion

Understanding the underlying patho-physiology of toxin induced arrhythmias improves our diagnosis and treatment of such problems