Toxicology

1. Approaching the Poisoned Patient!!

2. Objectives Provide a general overview of toxicology How to approach the poisoned patient Understanding common toxidromes

3. What is Toxicology What is it not a poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison. -Paracelsus (1943-1541), the Renaissance Father of Toxicology, in his Third defence

4. Why do people OD? Significant portion intend to die at time of overdose Most want to escape an intolerable situation or state of mind Small minority of patients want to punish someone or make someone feel guilty Mental health difficulties particularly, depression, ETOH or substance misuse, and personality disorders are frequently seen Inability to tolerate life stressor or events, relationship breakdowns, anniversaries of bereavement, ect. Mitchell, A. Dennis, M. Self harm and attempted suicide in adults: 10 practical questions and answers for emergency department staff . Emerg Med J, 2006: 26, 251-255

5. What Drugs do they OD on? ETOH Paracetamol Benzo’s Antipsychotics Antidepressants Antiepileptic Opiods And many many more!!!

6. Risk Assessment RRSIDEAD Approach Resuscitation Risk Assessment Supportive Care & Monitoring Investigations Decontamination Enhanced Elimination Antidotes Disposition

7. Resuscitation Airway Breathing Circulation Control seizures Correct hypoglycaemia Correct hyperthermia Consider resuscitation antidotes

8. Risk Assessment Agent Dose Time s ince ingestion Clinical features and course Patient factors Geographical location

9. Supportive Care & Monitoring Supportive Care Airway : Intubation Breathing: O2, Ventilation Circulation: IVIH, Inotropes , Defib or pacing Sedation: Titrate Benzo’s Seizure control/prophylaxis: Titrate Benzo’s Metabolic: control pH, normoglycaemia Fluids & Electrolytes: Monitor Renal function: hydrate, haemodialysis General : Bladder care ? IDC, Nutrition, DVT & Stress ulcer prophylaxis , PAC, Monitor mental state

10. Can good supportive care can be done at home?

11. Supportive Care & Monitoring Monitoring & investigation: 12 lead ECG Paracetamol Level BSL below 4 correct with D50 Temp above 38.5 requires continuous monitoring

12. Drug Levels Paracetamol Cabamazepine Lithium Salcicylate Digoxin Methanol Theophyline Ethanol Methotrexate Valproic Acid Ethylene glycol Iron Phenobarbitone

13. The ECG in TOX Valuable inexpensive screening tool QRS widening R/T sodium channel blockade, common with TCA overdose QT prolongation is a potassium channel effect associated with TDP, common in some antidepressant, antiarrythmics, & antipsychotic overdoses.

14. Urine Drug Screen Why don’t we do it? In general it rarely if ever changes management. Expensive Takes 1-2 days to get back When would we consider it?

15. Gastrointestinal Decontamination Methods: Induced Emesis (Syrup of ipecac) Gastric Lavage Activated Charcoal Whole Bowel Irrigation Activated charcoal has most benefits in a limited number of poisoning, other methods have limited if any evidence to support their use.

16. Enhanced Elimination Multiple-dose activated charcoal Urinary alkalinisation Haemodialysis and haemofiltration Charcoal haemoperfusion

17. Antidotes Limited number of antidotes available for limited number of poisonings. Common Antidotes: NAC Naloxone Sodium Bicarb Digoxin Immune Fab 5. Octreotide

18. Common Complications in the Critically Poisoned Patient Aspiration Pneumonia ARDS ARF DVT/PE Rhabdomyolysis Compartment Syndrome Hepatotoxicity

19. Disposition The patients journey can be: RESUS ICU Assessment Obs ward Psych Or patients with DSP need Pysch R/V

20. Poisoning in Children Most paediatric poisoning are benign, as children generally ingest small quantities. Always base your assessment on worse case scenario: The time of ingestion is assumed to be the latest possible time Assume all missing or unaccounted for agent(s) have been ingested Do not attempt to account for spillage, which is difficult to estimate If more than child involved, it is assumed that each child ingested all the missing or unaccounted for agent(s)

21. 2 tablets that can KILL a 10kg toddler Agent Features of Toxicity Amphetamines Methamphetamine MDMA Agitation, confusion, hypertension, hyperthermia Calcium channel blockers Delayed onset of bradycardia, hypotension, conduction defects, refractory shock Chloroquine Hydroxychloroquine Coma, seizures, cardiovascular collapse Dextropropoxyphene Ventricular Tachycardia Opiods Oxycodone Methadone Morphine sulfate Diphenoxylate/atropine Coma, respiratory arrest, may be delayed with controlled release products Propanolol Coma, seizures, ventricular tachycardia, hypoglycaemia Sulfonylurea's Hypoglycaemia onset can be delayed up to 8 hours Theophylline Seizures, SVT, vomiting Tricyclic antidepressants Coma, seizures, hypotension, ventricular tachycardia

22. Management of child who ingest unidentified poison Admit for minimum of 12-hour observation Ensure health care facility can cope Defer IV access until evidence of toxicity Check BSL at presentation and on D/C Monitor GCS & vital signs Cardiac monitor if decreased GCS or abnormal vital signs D/C during daylight hours

23. Poisoning in Pregnancy Need to assess risk to fetus or infant if lactating Management rarely differs from non pregnant patients Agents that pose greater risk to fetus: Carbon Monoxide Methaemoglobin-inducing agents Lead Salicylates Need to provide risk/benefit analysis if breastfeeding is to continue as the mother recovers

24. Poisoning in the Elderly Can be challenging to manage R/T co-morbidities, decreased physiological reserve, and multiple prescribed medications. Higher complication rate and longer hospital admission: Pharmacokinetic changes: Delayed gastrointestinal absorption Decreased protein binding ^ free drug levels Reduced hepatic metabolic function Decreased GFR which impairs elimination

25. Common poisoning in the Elderly Digoxin Metformin Lithium Disposition= Generally elderly patients end up in Gen Med units for prolonged periods of care

26. Toxidromes

27. Coma Patients presenting with coma have generally overdosed on a drug with CNS depressant effects. Can be caused by secondary effects: Hypoxaemia Hypoglcaemia Hyponatraemia Hypotension Seizures Cerebral oedema

28. Coma Management RRSIDEAD Good supportive care & airway management Treat secondary effects Look at what else can cause coma Neurotrauma Metabolic encepathopathy Menigioencephalopathy Space occupying lesion Patients generally go to ICU, till conscious states improve Look for complication’s (Asp Pneumonia)

29. Why do we use Diazepam so much in TOX? Good safety profile Long half life Controls agitation well Used to treat toxic seizures Generally drug of choice in managing withdrawals Dose adult 5-10mg, child 0.1-0.3mg/kg/dose every 3-5mins

30. Anticholinergic Syndrome Results from the competitive, reversible blockade of central & peripheral cholinergic blockade. Is potentially life threatening Diagnosed clinically by agitated delirium and peripheral muscarinic blockade History of ingestion of known anticholinergic agent

31. Types of Anticholinergic Agents Antipakinson drugs (benztropine, amantadine) Antihistamines (prometazine, doxylamine) Antitussives (dextromethorphan) Antidepressants (TCA) Antipsychotic agents including atypical (Haloperidol, olazapine, Quetiapine) Anticonvulsant agents (carbamazapine) Motion sickness agents (hyoscine-scopolamine) Antimuscarinic agents (Atropine) Topical ophthalmological agents Bronchodilators (Ipratropium) Urinary antispasmodic agents (oxybutynin) Muscle relaxants Plants & herbal remedies (Selected mushrooms)

32. Clinical Features of Anticholinergic Syndrome Central Peripheral Agitated delirium characterised by: Mydriasis Fluctuating mental status Tachycardia Confusion Dry mouth Restlessness Dry skin Fidgeting Flushing Visual hallucinations Hyperthermia Picking at objects in the air Sparse or absent bowel sounds Mumbling slurred speech Urinary retention Disruptive behaviour Tremor Myoclonus Coma Seizures (rare)

33. Remember the saying!!! Hyperthermia (HOT as a hare) Flushed (RED as a beet) Dry Skin (DRY as a bone) Dilated pupils (Blind as a bat) Delirium, hallucinations (Mad as a hatter) Tachycardia Urinary Retention

34. Management Good Supportive Care IV fluids IDC Diazepam to control agitation Avoid drugs with anticholinergic effects Antidote: Physostigimine Reverse anticholinergic delirium in selected patients that don’t respond to benzo’s

35. Serotonin Syndrome Clinical diagnosis based on history of ingestion of one or more serotonergic agents, the presence of characteristic symptoms, & high index of suspicion Clinical features fall into 3 categories CNS Autonomic Neuromuscular

36. Clinical features of serotonin syndrome CNS Autonomic Neuromuscular Apprehension Flushing Tremor * Agitation, psychomotor delirium* Mydriasis* Clumsiness Hallucinations Sweating * Hyperreflexia * Seizures* Tachycardia * Clonus * Coma Hyperthermia * Myoclonus * Hypertension * Increased limb tone (lower limbs > upper limbs Hypotension Rigidity Clonus & Hyperreflexia are highly diagnostic of serotonin syndrome Diarrhoea *

37. Life threatening serotonin syndrome Characterised by: Generalised rigidity Autonomic instability Delirium Coma Hyperthermia Secondary multiple-organ failure

38. Agents implicated in serotonin syndrome SSRIs ( fluoxetine, setraline, paroxetine ) SNRIs ( venlafaxine, citalopram, bupropion ) TCAs ( amitriptyline, dothiep ) MAOIs ( phenelzine, moclobemide ) Lithium Analgesic ( pethidine, tramadol, dextromethorphan ) Antiemetics ( metaclopramide, ondansetron ) Anticonvulsants ( valproic acid ) Drugs of abuse ( amphetamine, MDMA )

39. Managing Serotonin Syndrome RRSIDEAD Check BSL Check temp >38.5 continuous core monitoring, temp > 39.5 paralysis and intubate Give benzo’s to achieve gentle sedation HT & tachycardia generally respond to benzo’s, if refractory trial of GTN infusion Antidote: Cyproheptadine, given orally or via NG

40. The Tox Bible

41. THE END!!