May 2, 2023

DRUGS ALTERING

ECGDr. AMREEN SABA ATTARIYA

POST GRADUATE STUDENTDEPT OF PHARMACOLOGY

M.R. MEDICAL COLLEGE, GULBARGA INDIA

Dr.ASA:DrugsAlteringECG

OverviewItroductionConduction Pathways Systematic InterpretationDrugs altering ECGSummaryReferences

May 2, 2023Dr.ASA:DrugsAlteringECG

IntroductionNumerous toxins and drugs that can cause, in overdose, electrocardiogram (ECG) changes.

Abnormal ECG encountered in a specific toxicity can challenge experienced physicians.

Need for serious knowledge of basic cardiac physiology.

May 2, 2023Dr.ASA:DrugsAlteringECG

Conduction Pathways

May 2, 2023Dr.ASA:DrugsAlteringECG

P wave = atrial depolarisation.

PR Interval = impulse from atria to ventricles.

QRS complex = ventricular depolarisation.

ST segment = isoelectric - part

T wave = ventricular repolarisation.

QT Interval = onset of depolarisation to the completion of repolarization of the ventricles.

May 2, 2023Dr.ASA:DrugsAlteringECG

Interpretation

May 2, 2023Dr.ASA:DrugsAlteringECG

FOLLOW THE STEPS

May 2, 2023Dr.ASA:DrugsAlteringECG

1. Rate2. Regularity3. Intervals4. Rhythm5. Axis

Normal RAD LAD No Man’s Land

6. Waveform MorphologyPeaked/biphasic P wavesQRS changes

BBB/conduction delayLow or High VoltagePacer

T-waves Inversions7. ST Segment

ElevationDepression

8. Q-Waves

1. Rate = Number of P’s (atrial) R’s (ventricular) per minute (6 second [30 squares] X 10 = minute rate).

2. Rhythm = Regular or irregular. Map P-P and R-R intervals.

P rate: 8 x 10 = 80 R rate: 8 x 10 = 80

Interpretation

May 2, 2023Dr.ASA:DrugsAlteringECG

3. P wave = present, 1 per QRS, shape, duration, voltage.

4. P-R interval = length (0.12 - 0.2 sec = <1 big square), isoelectric.

Interpretation

May 2, 2023Dr.ASA:DrugsAlteringECG

5. QRS = duration, voltage

6. ST Segment = shape, isoelectric with PR segment

Interpretation

May 2, 2023Dr.ASA:DrugsAlteringECG

7. T wave = shape, direction

8. QT interval = length (R-R/2 or QTc <0.40 sec)

Interpretation

May 2, 2023Dr.ASA:DrugsAlteringECG

Axis determination

NormalRADLAD

May 2, 2023Dr.ASA:DrugsAlteringECG

Abnormalities: Supraventricular

arrhythmias Atrial Fibrillation Atrial Flutter Supraventricular Tachycardia (SVT)

• Premature Ventricular Complexes (PVCs)

Abnormalities: Ventricular arrhythmias

May 2, 2023Dr.ASA:DrugsAlteringECG

Conduction PathwaysSupraventricular Narrow QRS complex

Ventricular Wide QRS complex

May 2, 2023Dr.ASA:DrugsAlteringECG

12 lead EKGBipolar leads : I, II, III

May 2, 2023Dr.ASA:DrugsAlteringECG

12 lead EKGUnipolar Augmented Leads

aVRaVFaVL

May 2, 2023Dr.ASA:DrugsAlteringECG

12 lead EKGPrecordial Leads: V1 V2 V3 V4 V5 V6

May 2, 2023Dr.ASA:DrugsAlteringECG

Leads I, aVL, V5, V6 lateral leads.Leads II, III, aVFinferior leads.Leads V1 to V4anterior chest leads.Leads V1, V2 anterior septal leads

May 2, 2023Dr.ASA:DrugsAlteringECG

Main mechanisms involved

Depressant action(Na+, Ca2+, K+, Na+-K+ ATPase blockers)Action on ANS & its sites of CVS actionOther electrolyte imbalances made by drugs.

May 2, 2023Dr.ASA:DrugsAlteringECG

May 2, 2023Dr.ASA:DrugsAlteringECG

Membrane – depressant drugs and toxinsSodium channel blockers

Slow Calcium Channel Blockers (CCB)Outward potassium channel blockersSodium–potassium ATPase blockers

May 2, 2023Dr.ASA:DrugsAlteringECG

Na+ channel blockers(Inhibitors of fast Na+ channels)

May 2, 2023

CVS drugs Type Ia antiarrhythmicsType Ic antiarrhythmics-Propranolol and other membrane depressant beta-blockersVerapamil, Diltiazem

Psychiatric drugs

CarbamazepineCyclic antidepressantsNeurolepticsAntipsychotics

Other drugs AmantadineDiphenhydramineChloroquine, HydroxychloroquineOrphenadrineNarcotic pain relievers (Propoxyphene)

Illicit drugs CocaineToxins Quinine, Saxitoxin, TetrodotoxinDr.ASA:DrugsAlteringECG

May 2, 2023*Holstege et al., 2005

Dr.ASA:DrugsAlteringECG

ECG changesQRS widening

RBBB pattern

R wave elevation in aVR lead

Rightward deviation of QRS axis

VT & VF

Bradycardia with wide QRS complex

Asystole

ST/T changes consistent with ischemia (cocaine toxicity)

May 2, 2023Dr.ASA:DrugsAlteringECG

May 2, 2023

ACUTE POISONING WITH AMITRIPTYLINE

NORMAL ECG

Sinus tachy 148/min, QRS>/0.12sec, Rwave elev in aVR, QT prol, RAD

Dr.ASA:DrugsAlteringECG

May 2, 2023

SINE WAVE PATTERN

Dr.ASA:DrugsAlteringECG

May 2, 2023

RIGHT BUNDLE BRANCH BLOCKDiagnostic Criteria

•Broad QRS > 120 ms•RSR’ pattern in V1-3 (‘M-shaped’

QRS complex)•Wide, slurred S wave in the lateral

leads (I, aVL, V5-6)QRS >120ms

Slurred SWave

Dr.ASA:DrugsAlteringECG

Slow CCB

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG ChangesSinus bradycardiaReflex tachycardia (ex. Nifedipine)Varying degrees of AV blockSinus arrest with AV junctional rhythmAsystoleWide QRS complexST/T changes

May 2, 2023Dr.ASA:DrugsAlteringECG

ACUTE POISONING WITH VERAPAMIL IN A 61yr OLD FEMALE

May 2, 2023

NORMAL ECG

Sinus brady 41/min, minor RBBB, QTprol

Dr.ASA:DrugsAlteringECG

Outward K+ channel blockers

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG ChangesQT interval prolongationT- or U-wave abnormalitiesPremature ventricular beats (PVP) TdPSinus tachycardia

May 2, 2023Dr.ASA:DrugsAlteringECG

May 2, 2023Dr.ASA:DrugsAlteringECG

May 2, 2023Dr.ASA:DrugsAlteringECG

Na+-K+ ATPase Blockers

May 2, 2023Dr.ASA:DrugsAlteringECG

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG Changes*

May 2, 2023

Excitant activity: AF, Afl, VT VFSuppressant activity: sinus bradycardia, BBB, complete AV block.Combination

*Gordon, 2006; Lapostolle & Borron, 2007Dr.ASA:DrugsAlteringECG

May 2, 2023

The morphology of the QRS complex / ST segment“SLURRED”, “SAGGING” “SCOOPED” ,“REVERSE TICK”, “HOCKEY

STICK” OR“SALVADOR DALI’S MOUSTACHE”!

Dr.ASA:DrugsAlteringECG

May 2, 2023

BIPHASIC T wave with an initial -ve deflection and terminal +ve deflection(v4-6)

First part of the T wave is typically continuous with the depressed ST segment.

Terminal T +ve deflection may be peaked.

Or have a prominent u wave superimposed upon it.

T wave DIGOXIN effect

Dr.ASA:DrugsAlteringECG

May 2, 2023

DIGOXIN EFFECT

NORMAL ECG

Sagging ST segments are most evident in the lateral leads V4-6, I, aVL

Dr.ASA:DrugsAlteringECG

Drugs and toxins acting on ANSBeta-adrenergic blockers

Other sympathetic – inhibitors (other than BB)Sympathomimetic drugs and toxinsAnticholinergic drugs and toxinsCholinomimetic drugs and toxins

May 2, 2023Dr.ASA:DrugsAlteringECG

Beta Blockers

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG changes*

May 2, 2023*Gordon, 2006; Holstege et al., 2006; Brubacher, 2007

Dr.ASA:DrugsAlteringECG

Beta Blockers that Prolong QT intervalSOTALOL

ACEBUTALOL

PROPRANOLOL

May 2, 2023

TdPDr.ASA:DrugsAlteringECG

Other sympathetic – inhibitors (other than

BB)MethyldopaClonidine and other imidazoline derivativesReserpine, GuanethidinePrazosin and other alpha-blockers

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG ChangesSinus, atrial, junctional and ventricular bradyarrhythmiasFirst degree AV block

May 2, 2023Dr.ASA:DrugsAlteringECG

Sympathomimetic toxicity

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG changesSinus tachycardiaAtrial tachycardiaVentricular premature beatsVT, VFMyocardial ischemia or infarction (cocaine, amphetamines, or hydrocarbons ingestion)

May 2, 2023Dr.ASA:DrugsAlteringECG

Anticholinergic toxicity

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG ChangesSinus & atrial tachycardiaPremature ventricular beats

May 2, 2023Dr.ASA:DrugsAlteringECG

Cholinomimetic toxicity

May 2, 2023Dr.ASA:DrugsAlteringECG

ECG ChangesSinus bradycardiaAV blockSinus tachycardia (seen in early stages of cholinesterase inhibition and nicotine poisoning due to ganglionic stimulation)VT associated with QT interval prolongationAsystole

May 2, 2023Dr.ASA:DrugsAlteringECG

May 2, 2023Dr.ASA:DrugsAlteringECG

Drugs of abuse*

May 2, 2023*Albertson, 2004; Albertson et al., 2007, a; Delgado, 2007; Quang, 2007; Traub, 2007; Yip et al.,2007

Dr.ASA:DrugsAlteringECG

Electrolyte Disturbances as AE

HYPERKALEMIA

Peaked T waves

PR prolongation and P wave flattening

QRS widening

HYPOKALEMIA – ST depression, T wave flattening, U waves

HYPOCALCEMIA – Prolonged QT interval

HYPERCALCEMIA – Shortened QT interval

May 2, 2023Dr.ASA:DrugsAlteringECG

May 2, 2023Dr.ASA:DrugsAlteringECG

HYPERKALEMIA

May 2, 2023Dr.ASA:DrugsAlteringECG

LITHIUMCompetes with Na+, K+, Ca2+ & Mg2+ions

QT prolongation, ST segment changes & T wave changes.Sinus bradycardia, AVblocks, cardiovascular compromise.ECG changes chronic overdoses>>acute overdoses*

May 2, 2023Dr.ASA:DrugsAlteringECG

*Linakis J, Woolf A. Clinical features of acute versus chronic lithium overdose. Vet Human Toxicol 1989;31:370.

Combination to be avoided(D/I)ACEI + AMILORIDE/TRIAMTERENE hyperkalemia

LITHIUM + ACEI levels of Li.LITHIUM + LOOP DIURETICS Li.WARFARIN + AMIODARONE risk of bleeding.DIGOXIN + THIAZIDES digitalis toxicity.CCB + BETA BLOCKER bradycardia.SIDENAFIL + NITRATES severe hypotension cardiac death.ACEI + K+SPARING DIURETIC hyperkalemia.

May 2, 2023Dr.ASA:DrugsAlteringECG

DRUGS WITHDRAWN FROM MARKET DUE TO CARDIOTOXICITY

DRUGS

ASTEMIZOLE

CISAPRIDE

PROPOXYPHENE

FEN-PHEN(FENFLURAMINE + PHENTERMINE)

ROSIGLITAZONESIBUTRAMINE

TERFENADINE

ROFECOXIB

YEAR OF WITHDRAWAL

1999

2000

2010

1997

2010

1997

2004

REASON

FATAL ARRYTHMIAS

FATAL ARRYTHMIAS

HEART ATTACKS & STROKE

CARDIOTOXICITY

HEART ATTACK & DEATH

QT PROL & V.TACH

MI & STROKEMay 2, 2023Dr.ASA:DrugsAlteringECG

SummaryECG is a valuable source of information in poisoned patients and has the potential to enhance and direct their care.

Many drugs with no overt cardiovascular effects from therapeutic dosing become cardiotoxic in overdose.

Knowledge of drug PK PD & ADR profile is a mandatory thing before prescription.

Main blocker drugs that affect heart--Na+, K+ Ca++, Na-K ATPase.

Others being the one acting on ANS, drugs of abuse etc

Irrational use of drugs may create much financial burden to a country.

ECG should be examined extremely early in initial evaluation of most poisoned cases. May 2, 2023Dr.ASA:DrugsAlteringECG

REFERENCESAlbertson, T.E. (2004). Amphetamines, In: Poisoning & Drug Overdose, 4th Ed., Olson, K.R. et al. (Eds.), pp. 72-74, Lange Medical Books/McGraw-Hill, ISBN 0-8385-8172-2, NewYork, USA.

Anderson, A.C. (2008). Management of Beta-Adrenergic Blocker Poisoning. Clinical Pediatric Emergency Medicine, Vol. 9, No. 1, (March, 2008), pp.4-16, ISSN 1522-8401.

Holstege, C.; Baer, A. & Brady, W.J. (2005). The ECG toxidrome: the ECG presentation of hydrofluoric acid ingestion. American Journal of Emergency Medicine,Vol. 23, No.2, (March 2005), pp.171-176. ISSN 0735-6757.

Lionte C et al: Toxic and Drug-Induced Changes of the ECG, ”Gr.T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Puhr J et al: Lithium overdose with ECG changes suggesting ischemia, Toxicology observation North Carolina.

May 2, 2023Dr.ASA:DrugsAlteringECG