drug induced arrhythmia dr. sh tsui 15 june 2005
TRANSCRIPT
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