1. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac arrhythmia  Primary –quinidine–like drugs, sympathomimetic drugs, calcium channel blockers, β– blockers, digitalis, chloroquine  Secondary to metabolic/electrolyte abnormalities –salicylates, methanol, ethylene glycol

2. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiotoxic drugs  All patients should have –oxygenation and protection of airway –decontamination of the GIT l atropine pre–medication –correction of electrolyte abnormalities l acid base balance –cardioversion when appropriate –consultation

3. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac arrest  Successful resuscitation has been well documented after 8 hours of CPR  Overdose patients usually have –a reversible cause for their arrest –good general health –novel treatments for arrhythmias –cerebral protection

4. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Antidotes: asystole & bradycardia  Atropineeverything  Bicarbonate tricyclic antidepressants  Calcium calcium channel blockers  Diazepamchloroquine, organochlorines  Epinephrineeverything, β–blockers  Fab fragmentsdigoxin  Glucagonβ–blockers, CCBs

5. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 1  18 yo female admitted 3 hours after self–poisoning with –3.5 g of slow release verapamil (Isoptin SR) –6 g of paracetamol –4.5 g of tetracycline –1 g of pseudoephedrine  On arrival in casualty –pr 120, BP 110/80, RR 20, afebrile –drowsy but oriented and cooperative

6. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 1  GI decontamination –emesis before arrival –lavaged with return of green tablets –50 g of charcoal with sorbitol repeated 4 h later  Investigations –ECG l sinus tachycardia with normal QRS width –serum paracetamol at 4 h was 38 µmol/l l hepatotoxicity > 1300 µmol/l at 4 hours

7. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 1  In intensive care unit –16 hours post overdose –BP fell to 70/40 and then 50/30 –PR 50 –oxygen saturation dropped to 75 % –ECG l absent p waves l prominent u waves l normal QRS duration and QT interval

8. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 1  Treatment –IV atropine 0.6 mgs – no response –IV calcium gluconate l 6 g over 20 minutes l further 6 g over the next hour –pr 60, sinus rhythm, BP 100/80 –oxygen saturation > 95 % –infusion of 10% calcium gluconate at 2 G/h for 10 hours –she was also given 2.5 L IV fluids

9. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 1  Outcome –non–cardiogenic pulmonary oedema –twenty four hours post admission l largely recovered, sinus rhythm PR 60, BP 115/70 –peak serum Ca was 4.8 (2.18–2.47 mmol/l) –serial verapamil levels at 6, 18, 22 and 46 hours were 616, 2374, 2518 and 1006 ng/ml l range during usual therapy –100–300 ng/ml

10. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 2  38 yo female admitted after self–poisoning with –amitriptyline 2525 mg –dothiepin 1650 mg  Found unconscious with suicide note carefully documenting tablets –last seen 9 a.m., brought in by ambulance at 6 p.m. –later said she had read that 2.5 g was a lethal dose

11. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 2  No past medical history  Depressed for several months, treated by a psychiatrist  On examination –absent gag –unconscious, flexes to pain –PR 40, BP 130/100, afebrile –hypoventilating, 0 2 saturation 94 % –flushed, dilated pupils, reduced bowel sounds

12. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 2  Investigations –FBC –EUC –paracetamol level –ECG –CXR ? aspiration  GI decontamination –gastric lavage and activated charcoal

13. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 2  Treatment and outcome –given NaHC0 3 IV –intubated and hyperventilated –IV normal saline –ABGs monitored to keep pH 7.5 –serial ECGs –prolonged unconsciousness –extubated 40 hours later –no long term sequelae

14. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 3  26 yo female –found unconscious by police in caravan –empty bottle of tablets with label removed –no relatives/other history available  On examination –PR 140, BP 120/80, afebrile –unconscious –GCS 6

15. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 3  Investigations –ECG l QRS width 120 ms l PR interval 200 ms –CXR l aspiration pneumonia  Management –intubated, lavage, charcoal, antibiotics

16. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Cardiac case 3  Outcome –sudden deterioration 2 hours later –bradycardia –asystole –unable to be resuscitated

17. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Tricyclic antidepressants  Ingestion of 15–20 mg/kg is potentially fatal  Mechanism of action –block re–uptake of noradrenaline and serotonin –competitive antagonists at H 1 and H 2 receptors –anticholinergic effects –membrane effects on sodium channel, quinidine–like effect

18. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Toxico–kinetics  Absorption and distribution –highly lipid soluble l rapidly absorbed l high volume of distribution –delayed absorption due to anticholinergic effect in GIT –pH dependent protein binding > 95% l large variation in amount of free TCA l a change in the pH from 7.38 to 7.50 produces a 21% reduction in free TCA

19. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital TCA management  General –supportive care, ABG, ECG, electrolytes –lavage, charcoal with sorbitol/mannitol  CNS toxicity –seizures l IV diazepam l IV phenytoin (15–18 mg/kg) –anticholinergic delirium l benzodiazepines, haloperidol l seizure and fever consider physostigmine

20. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital TCA management  Arrhythmias –plasma alkalinisation to pH ~ 7.5 l sodium bicarbonate, hyperventilation –drug treatment l acute –magnesium –sotalol –lignocaine l prophylactic –phenytoin –overdrive pacing

21. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital TCA management  hypotension –volume expansion –pH correction –alpha agonists e.g. noradrenaline –inotropics e.g. dopamine, dobutamine