Cardiac arrhythmia N Primary quinidinelike drugs sympathomimetic drugs

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

Cardiotoxic drugs N 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 Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Cardiac arrest N N 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 Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Antidotes: asystole & bradycardia N N N N Atropine Bicarbonate Calcium Diazepam organochlorines Epinephrine Fab fragments Glucagon everything tricyclic antidepressants calcium channel blockers chloroquine, everything, β–blockers digoxin β–blockers, CCBs Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Cardiac case 1 N 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 N On arrival in casualty – pr 120, BP 110/80, RR 20, afebrile Clinical Toxicology– & Pharmacology, Newcastle Mater Misericordiae Hospital drowsy but oriented and cooperative

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

Cardiac case 1 N 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 absent p waves l prominent u waves l normal QRS duration and QT interval l Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Cardiac case 1 N Treatment – IV atropine 0. 6 mgs – no response – IV calcium gluconate 6 g over 20 minutes l further 6 g over the next hour l – 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 Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Cardiac case 1 N 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 range during usual therapy Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital l

Cardiac case 2 N 38 yo female admitted after self–poisoning with – amitriptyline 2525 mg – dothiepin 1650 mg N 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 Clinical Toxicologydose & Pharmacology, Newcastle Mater Misericordiae Hospital

Cardiac case 2 N 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, 02 saturation 94 % – flushed, dilated pupils, reduced bowel sounds Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

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

Cardiac case 2 N Treatment and outcome – given Na. HC 03 IV – intubated and hyperventilated – IV normal saline – ABGs monitored to keep p. H 7. 5 – serial ECGs – prolonged unconsciousness – extubated 40 hours later – no long term sequelae Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

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

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

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

Tricyclic antidepressants N N 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 Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Toxico–kinetics N Absorption and distribution – highly lipid soluble rapidly absorbed l high volume of distribution l – delayed absorption due to anticholinergic effect in GIT – p. H dependent protein binding > 95% large variation in amount of free TCA l a change in the p. H from 7. 38 to 7. 50 produces a 21% reduction in free TCA l Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

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

TCA management N Arrhythmias – plasma alkalinisation to p. H ~ 7. 5 l sodium bicarbonate, hyperventilation – drug treatment l acute – magnesium – sotalol – lignocaine l prophylactic – phenytoin – overdrive pacing Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

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