Poisons and Poisoning

Dr Ian Wilkinson Clinical Pharmacology Unit

Accidental?

Deliberate?

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

General Comments
Try and get as much history as possible including witnesses People truly wanting to commit suicide often lie Remember the ABCs: Airway Clear mouth & throat, gag reflex O2 saturation, ABGs Breathing Circulation Venous access, IV fluids if shocked

Assess GCS Examination

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

Care with names!

Distalgesic Anadin

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

Management
Supportive
Correct hypoxia, hypotension, dehydration, hypohyperthermia, and acidosis Control seizures

Monitor
TPR, BP, ECG, Oxygenation, GCS

General
Absorption Elimination Specific antidotes

 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) Doesnt bind heavy metals, ethanol, acids

 Elimination
Multiple dose activated charcoal
Quinine, phenobarbitone

Charcoal haemoperfusion
Barbiturates, theophylline

Diuresis Urinary alkalinization Dialysis

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

Paracetamol Metabolism

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

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

Treatment Graph

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)

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

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 (HCO3-) Levels > 700 mg/L before rehydration, renal failure or pulmonary oedema consider haemodialysis

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

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

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 CO2 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

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

Tricyclic OD Initial ECG

Tricyclic OD Recovery ECG

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.

Other agents
Opiates Iron Lead Digoxin Calcium blockers Ethylene glycol Lithium Naloxone Desferrioxamine Sodium EDTA FAB Calcium Ethanol Dialysis