1. Poisons and Poisoning Dr Ian Wilkinson Clinical Pharmacology Unit

2. Accidental?

3. Deliberate?

4. Suicides in the UK ~6,300 suicides pa –20% of deaths in young people ~140,000 attempted suicides (parasuicides) –Most common 15-19 year old females –Most common method is poisoning 50% paracetamol

6. General Comments Try and get as much history as possible including witnesses People truly wanting to commit suicide often lie Remember the ABCs: –AirwayClear mouth & throat, gag reflex –BreathingO 2 saturation, ABGs –CirculationVenous access, IV fluids if shocked Assess GCS Examination

7. History When, what, how much ? Why? Circumstances PMHx, Drug history Psychiatric history Assess mental status and capacity

8. Care with names! Distalgesic Anadin

9. Investigations Always check blood glucose. Send blood & urine for toxicology screening. ALWAYS measure paracetamol & salicylate levels –Failure to diagnose & treat is negligent. U&Es, LFTs, glucose, ABG, clotting, bicarbonate ECG, CXR Specific blood levels

10. Management Supportive –Correct hypoxia, hypotension, dehydration, hypo- hyperthermia, and acidosis –Control seizures Monitor –TPR, BP, ECG, Oxygenation, GCS General –  Absorption –  Elimination –Specific antidotes

11.  Absorption NEVER Ipecacuanha Gastric lavage –Only if within 1 hour & life-threatening amount –Never for corrosives –If  LOC intubate Activated charcoal –50 g single or repeated dose (  elimination) –Doesn’t bind heavy metals, ethanol, acids

12.  Elimination Multiple dose activated charcoal –Quinine, phenobarbitone Charcoal haemoperfusion –Barbiturates, theophylline Diuresis Urinary alkalinization Dialysis

13. Paracetamol Overdose Most common drug taken in overdose Few symptoms or early signs As little as 12g can be fatal Hepatic and renal toxin –Centrolobular necrosis More toxic if liver enzymes induced or reduced ability to conjugate toxin

14. Paracetamol Metabolism

15. Management General measures including –U&Es, LFTs, glucose, clotting ABG, bicarbonate, paracetamol and salicylate levels –Activated charcoal <8 hours –Take level after four hours –Start N-aceylcysteine if above treatment line –Patients are usually declared fit for discharge from medical care on completion of its administration. However, check INR, creatinine and ALT before discharge. Patients should be advised to return to hospital if vomiting or abdominal pain develop or recur

16. Management 2 >8 hours –Urgent action required because the efficacy of NAC declines progressively from 8 hours after the overdose –Therefore, if > 150mg/kg or > 12g (whichever is the smaller) has been ingested, start NAC immediately, without waiting for the result of the plasma paracetamol concentration >24 hours –Still benefit from starting NAC

17. Treatment Graph

18. N-acetylcysteine Supplies glutathione Dosage for NAC infusion - ADULT –(1) 150mg/kg IV infusion in 200ml 5% dextrose over 15 minutes, then –(2) 50mg/kg IV infusion in 500ml 5% dextrose over 4 hours, then –(3) 100mg/kg IV infusion in 1000ml 5% dextrose over 16 hours Side-effects –Flushing, hypotension, wheezing, anaphylactoid reaction Alternative is methionine PO (<12 hours)

19. Aspirin Overdose Early features –hyperventilation, sweating, tremor, tinnitus, nausea / vomiting, or hyperpyrexia Metabolic features –Hypo- or hyper-glycaemia, hypokalaemia, respiratory alkalosis, metabolic acidosis Others –renal failure, pulmonary oedema, seizures, coma, death

20. Management General measures Bloods –Salicylate (paracetamol) level >2 hours, and after 2hrs –>700 potentially lethal –>500 moderate-severe poisoning –U&Es, glucose, ABG, bicarbonate Activated charcoal Rehydrate, monitor glucose, correct acidosis and K+ If levels >500mg/L alkalanize urine (HCO 3 - ) Levels > 700 mg/L before rehydration, renal failure or pulmonary oedema consider haemodialysis

21. TCAs -Introduction Potentially fatal (2.5 to 3.5g of amitriptyline) Neurological and cardiac problems common –Toxicity due to anticholinergic actions, and direct quinidine-like effect on the myocardium Serious toxicity results from:- –Ventricular dysrhythmias –Seizures –Hypotension –Respiratory depression Initial symptoms at presentation may be trivial, and most major problems occur within 6hrs

22. TCAs-Features of poisoning Peripheral –Sinus tachycardia, hot dry skin, dry mouth, urinary retention, hypotension and hypothermia may occur CNS –Dilated pupils, ataxia, nystagmus, squint,  LOC, coma, seizures, respiratory depression,  tone,   reflexes,  plantars ECG –prolonged PR and QRS interval,  QT –ventricular dysrhythmias

23. TCAs -Management GCS and QRS, best indicators of toxicity Supportive –do not use flumazenil if benzo taken Check airway, maintain ventilation, correct hypoxia –Check ABG, if  CO 2 requires ventilation Correct hypotension (crystalloids) Gastric lavage if within 1 hr, and activated charcoal Rx fits and agitation with diazepam Rewarm slowly if hypothermic Close monitoring for 24hrs

24. TCAs- Dysrhythmias Carful ECG monitoring is required –QRS interval is a guide to cardiac toxicity (>100ms) Avoid antidysrhythmic drugs. They may make matters worse Correct hypoxia and acidosis. Aim for a pH of 7.45-7.50 (no higher) –use iv boluses of sodium bicarbonate Sodium loading may also help Prolonged CPR may be of use

25. Tricyclic OD – Initial ECG

26. Tricyclic OD – Recovery ECG

27. Benzodiazepine Overdose Deaths from poisoning with benzodiazepines alone are rare, but may be lethal in combination with other CNS depressants Treatment is supportive and aimed at maintaining adequate ventilation whilst supporting cardiovascular depression Flumazenil (specific benzodiazepine antidote) is not licensed (in the UK) for routine use in benzodiazepine overdoses Flumazenil may induce seizures; particularly dangerous where tricyclic antidepressants have been taken Flumazenil, may however, be used in the differential diagnosis of unclear cases of multiple overdoses but expert advice is ESSENTIAL.

28. Other agents OpiatesNaloxone IronDesferrioxamine LeadSodium EDTA DigoxinFAB Calcium blockersCalcium Ethylene glycolEthanol LithiumDialysis