ELECTROCARDIOGRAPHIC CHANGES AS A PREDICTOR OF CARDIOVASCULAR TOXICITY

ELECTROCARDIOGRAPHIC CHANGES AS A PREDICTOR OF CARDIOVASCULAR TOXICITY IN ACUTE TRICYCLIC ANTIDEPRESSANT (AMITRIPTYLINE) OVERDOSE Pavlovski B, Becarovski N, Popovski N, Cibisev A, Trencevska L, Babulovska A Clinic of Toxicology and Urgent Internal Medicine. University Clinical Center. Skopje. Macedonia

BACKGROUND: • GENERAL VIEW ON CLINICAL TOXICOLOGY PRACTICE NOWADAYS • WORLD TRENDS • SLOWLY CHANGES IN PROFIL OF TOXICOLOGICAL CASES

BACKGROUND: NEW ANTIDEPRESSANT DRUGS SSRI (SPECIFIC SEROTONIN REUPTAKE INHIBITORS) AS FLUOXETINE-PROZAC PAROXETINE -SEROXAT FLUVOXAMINE – FEVARIN, FLAXIVRAL SERTRALINE –ASENTRA, ZOLOFT SLOWLY BECOME A PART OF OUR DAILY TOXICOLOGICAL PRACTICE.

AMITRIPTYLINE- (AMYZOL, TRIDEP, ELAVIL, LAROXYL, SAROTEN) STILL REMINDS THE MOST OFTEN USED DRUG IN ACUTE SUICIDAL POISONINGS INVOLVING ALL ANTIDEPRESSANT DRUGS (5 -6%) SLOWLY INCREASE

ACCORDING TO PROF. A. MONOV(Clinical Toxicology, Volume, Ist, 1995) REASONS FOR CARDIOVASCULAR TOXICITY • DIRECT TOXICITY EFFECT ON M CELLS • DIRECT EFFECT ON VASOMOTORES CENTERS • DISTURBANCES ON POTASSIUM-NATRIUM ON MIOFIBRILES HYPOVOLEMIA • • HYPOXEMIA ON MITOHONDRIAL LEVEL DISTURBANSES ON GLYCOGEN SYNTHESIS CORONARY ARTERY SPASM CONDUCTION DISTURBANCES

AMITRIPTYLINE CARDIOTOXICITY • MAIN REASONS • ANTICHOLINERGIC EFFECT-SINUS TACHYCARDIA • SYMPATOMIMETIC EFECTNORADRENALIN BLOCKADEPOTENTION TACHYCARDIA AND HYPERTENSION AND ARRHYTHMIAS • CHINIDIN LIKE EFECT-SLOW M CONTRACTILITY, FREQUENCE AND CORRONARY FLOW

OBJECTIVE: • THE AIM OF THIS STUDY WAS TO EVALUATE: • ELECTROCARDIOGRAPHIC CHANGES • URINE AND SERUM CONCENTRATIONS OF THE DRUG • TO CORRELATE CLINICAL PICTURES IN PATIENTS ACUTELY INTOXICATED BY AMITRIPTYLINE (AMYZOL).

• MATERIAL AND METHODS : THE STUDY WAS CARRIED OUT ON FORTY-FOUR CONSECUTIVE PATIENTS 31(71%) WOMEN 13(29%) MEN, ACUTELY INTOXICATED BY AMITRIPTYLINE. PARRTICIPANTS WERE TREATED IN INTENSIVE CARE UNIT DURING THE PAST TWO YEARS

• • TOTAL NUMBER--------- 44 WOMEN---------------31(71%) MEN------------------13(29% MEAN AGE-------------36, 5 years (from 18 to 60 years) • ATTEMPTS-------------ALL

A CORRELATION BETWEEN THE VALUES OF R/a. VR, R/Sa. VR AND QRS INTERVAL GREATER THAN 100 miliseconds WERE MADE. SEVERITY OF COMA SCALE(GLAZGOW COMA SCALE) ON ADMISSION WERE EVALUATED FOR EACH PATIENT. ECG, BLOOD PRESSURE AND RESPIRATORY RATE WERE CONTINUALLY MONITORED.

• URINE CONCENTRATIONS OF THE DRUG WERE DETERMINED USING THIN LAYER CHROMATOGRAPHY (TLC) AS A SCREENING TEST • SERUM CONCENTRATIONS WERE DETERMINED WITH FLUORESCENCE POLARIZATION IMMUNOASSAY TECHNIQUE (FPIA)

RESULTS: GCS FROM THREE TO TWELVE FOR ALL GROUP WERE RANGED. • ECG CHANGES: SINUS TACHYCARDIA WAS THE MOST COMMON ADVERSE OUTCOME FOR ALL GROUP. MULTIFOCAL EXTRASYSTOLES, CARDIAC CONDUCTION DISTURBANCES, DIFFERENT DEGREES OF ATRIOVENTRICULAR AND INTRAVENTRICULAR BLOCKS WERE OBSERVED ALSO. SERUM CONCENTRATIONS USING FPIA TECHNIQUE WERE RANGED FROM 232 TO 866/ng/ml.

R/a. VR WAS GREATER IN THOSE PATIENTS WHO HAD ARRHYTHMIAS OR SEAZURES THAN IN THOSE WHO DID NOT. SEAZURES OCCURRED IN 6(15%) PATIENTS AND MALIGNANT ARRHYTHMIAS IN 3 (7%) PATIENTS.

STATISTICAL ANALYSES • MULTIPLE LOGISTIC REGRESSION ANALYSE: • ECG CHANGE : R/a. VR of 3 mm of more -SIGNIFICANTLY PREDICTED THESE ADVERSE OUTCOMES

CONCLUSION: • ALTHOUGHT THE HISTORY AND PHYSICAL EXAMINATION PLAY AN IMPORTANT ROLE IN THE ASSESSMENT OF PATIENTS WITH TRICYCLIC ANTIDEPRESSANTAMITRIPTYLINE OVERDOSE, THE PRESENCE OF ANTIHOLINERGIC FEATURES ON EXAMINATION CANNOT PREDICT THE SEVERITY OF THE OVERDOSE.

SEVERAL CLINICAL VARIABLES, IN PARTICULAR ELECTROCARDIOGRAPHIC(ECG) CHANGES, HAVE BEEN PROPOSED AS A GUIDE TO DETERMINE THE SEVERITY OF THE TRICYCLIC ANTIDEPRESSANT POISONINGS. ECG CHANGES ARE VERY PRACTICAL AND USEFUL DATA FOR DIAGNOSTIC AND THERAPEUTIC APPROACH

THERE IS NO CORRELATION BETWEEN URINE, PLASMATIC CONCENTRATIONS AND CLINICAL PICTURES.