TOXICOLOGY Poisoning may be: Accidental – cyanide from burning furniture, an accumulation of toxic levels of a prescription drug, accidentally ingested by a child Social drug use Deliberate self harm Attempts to harm others What are the important questions you need to ask when taking a history from a patient with poisoning ? HISTORY What have they taken ? Type of preparation taken ? Any other substances taken ? Route of poisoning ? Time taken ? Previous poisoning attempts Psychiatric history Description of the event Intended results of poisoning SAD PERSONS score Be cynical – don’t presume they are being completely truthful – there may be social, family or mental health issues at play WHAT SHOULD YOU BE LOOKING FOR IN YOUR EXAMINATION ? EXAMINATION Should focus on: Identifying the underlying cause - Opioid overdose – small pupils, ↓ resp rate Identifying any complications from the overdose - GCS - Temp - Cardiovascular compromise - Inadequate respiration WHAT TOXIDROMES CAN YOU LOOK FOR ? TOXIDROMES A toxidrome : describe signs/symptoms that consistently result from particular toxins Groups drugs together according to these signs/symptoms Vital signs and end organ manifestations SYMPATHOMIMETIC TOXIDROME Drugs – caffeine, cocaine, amphetamines, Ritalin, LSD, theophylline, MDMA Mimics fight or flight Characteristics: Tachycardia, dysrhythmias Hypertension Delusions, paranoia Diaphoresis Seizures Hyperthermia Dilated pupils ANTICHLINERGIC TOXIDROME Drugs: Anticholinergics –Atropine, glycopyrrolate Antihistamines Antipsychotics – Chlorpromazine, Clozapine, Olanzapine, Quetiapine Antispasmodics –Oxybutynin Cyclic antidepressants –Amitriptyline, Nortriptyline Mydriatics – Cyclopentolate, Tropicamide Also carbamazepine, class 1A antiarrhythmics, certain plants - belladonna ANTICHLINERGIC TOXIDROME Anticholinergic poisoning commonly occurs but is frequently unrecognized The degree of central and peripheral anticholinergic effects vary depending on the drug or toxin involved There is a marked individual variation in response to the anticholinergic agents Children: particularly sensitive to anticholinergic agents due to receptor sensitivity Children with Down syndrome commonly have a genetically determined hypersensitivity to anticholinergic agents ANTICHLINERGIC TOXIDROME A mnemonic for recalling some of the signs and symptoms of anticholinergic poisoning: – Mad as a hatter –Blind as a bat – very dilated pupils – Dry as a bone - Blockade of cholinergic tone to salivary glands – ↓ salivation, dry mouth, intense thirst and difficulty swallowing – Red as a beetroot – flushing of the skin – Hot as a pistol – hyperthermia, sweat glands are blocked Symphatomimetic Anticholinergic Mydriasis Mydriasis Tachycardia/HTN Tachycardia/HTN Hyperthermia Hyperthermia Disorientation Disorientation Agitation Hallucinations Hallucinations Bowel sounds present Decreased bowel Diaphoresis sounds (unreliable) Dry skin/mucous membranes CHOLINERGIC TOXIDROME DRUGS: ORGANOPHOSPHATES, CERTAIN MUSHROOMS, PESTICIDES Muscarinic efects Nicotinic effects Defecation Tachycardia Urination Hypertension Miosis Muscle fasticulation Bradycardia paralysis Emesis Lacrimation Increased secretions sweating OPIOID TOXIDROME Drugs: morphine, codeine, tramadol, methadone, fentanyl, heroin, oxycodone Pin point pupils Altered mental status Decreased bowel sounds Respiratory depression WHAT OTHER DIAGNOSES DO YOU NEED TO BE WORRIED ABOUT ? SEROTONIN TOXICITY Drugs: MAOIs, SSRIs, SNRIs, cocaine, amphetamines, MDMA, levodopa, tramadol, TCAs, ondansetron, maxalon, lithium, fentanyl, carbamazepine Leads to neuroexcitation spectrum of toxicity The intensity of linical findings reflects the degree of serotonergic activity Abnormalities of: mental state – agitation, restlessness, confusion Motor system – clonus, myoclonus, tremor, hyperreflexia, hypertonia Autonomic nervous system – Diaphoresis / tachycardia / flushing / mydriasis SEROTONIN TOXICITY Majority present within 24 hours and most within six hours of a change in dose or initiation of a drug Intentional O.Ds often develop greater toxicity than accidental cases Clinical diagnosis Neuromuscular findings more pronounced in lower limbs Tachycardia, ↑BP, hyperthermia Complications – ARDS, DIC, rhabdomylosis, metabolic acidosis, AKI HUNTER SEROTONIN TOXICITY CRITERIA WHAT IS YOUR INITIAL MANAGEMENT GOING TO BE ? MANAGEMENT Airway Breathing Circulation Disability – GCS, pupils, neuro E - temperature Supportive measures Measures to reduce absorption Charcoal Whole bowel irrigation – iron, lithium, lead, drug packers, SR preps, ingestion of transdermal patches Antidotes – beware of Short half lifes Consider length of infusion and hospital suppies Can precipitate withdrawal Can be dangerous in themselves Some don’t act against any toxic metabolites already present e.g ethanol Toxbase ANTIDOTES Antidote Toxin Metabolism of action Acetylcysteine Paracetamol By production of cysteine which acts as a glutathione precursor. It also supplys additional thiol groups which bind directly with NAPQI – the reactive metabolite. Atropine Organophosphates Blocks the action of acetylcholine at muscarinic receptors Glucagon Beta blockers Stimulates adenyl cyclase to produce cAMP at a site distant from the beta receptor – produces effects similar to those of beta agonists resulting in ↑ myocardial contractility and heart rate Desferrioxamine Iron Binds free circulating iron in the plasma to form the octahedral iron complex ferrioxamine Dicobalt edetate Cyanide Forms relatively non toxic stable ion complexes (cobaltocyanides, cobalti- cyanides) with cyanide which are then excreted in the urine Digoxin specific Digoxin Has a greater affinity for digoxin than the tissue binding sites. The Fab antibody fragments fragments bind the intravascular free digoxin & then diffuse into the interstitial space binding free digoxin there Ethanol Ethylene glycol & Both metabolised by alcohol dehydrogenase. Ethanol is a competitive methanol antagonist for ADH and possesses a far greater affinity for the enzyme Antidote Toxin Metabolism of action Flumazenil Benzodiazepines A competitive inhibitor of drugs which act via the benzodiazepine receptors, specifically blocking their central effects. Fomepizole Ethylene glycol & A competitive inhibitor of alcohol dehydrogenase methanol Methionine Paracetamol Acts as glutathione precursor and replenishes glutathione stores which have been depleted due to paracetamol poisoning Naloxone Opioids A specific antagonist the acts competively at opioid receptors Penicillamine Heavy metals A chelation agent for certain heavy metals – copper, lead, mercury Pralidoxime Organophosphates Organophosphates inhibit acetylcholinesterase (AC-ase). Pralidoxime restores AC-ase activityby removing the bulky phosphate moiety from the phosphorylated AC-ase Protamine Heparin Has a greater affinity for heparin than AT III and is able to cause a dissociation of the heparin AT III complex in favour of the stable and inactive heparin protamine complex Sodium Thiosulphate Cyanide Acts as a substrate for the enzyme rhodanase which catalyses the conversion of cyanide to the relatively non toxic thiocyante WHAT INVESTIGATIONS SHOULD YOU REQUEST ? HOW USEFUL ARE THE LABORATORY LEVELS ? .