ACEM Primary
ED Primary Toxicology
Toxicology
Laboratory:
- ABG
- Electrolytes-> Anion Gap raised
- Organic acid metabolites (methanol/ethylene glycol)
- Lactic acidosis (cyanide, CO, metformin, ibuprofen, salicylates, any drug induced seizures, hypoxia or hypotension)
- Renal function
- CK elevated due to muscle necrosis (seizures) or rigidity
- Serum osmolality
- Normal = 280-290 mosm/L
- Osmol gap = measured – calculated, caused by ethanol/ methanol/ ethylene glycol/ isopropanol
- ECG
- QRS (widened in TCA)
- AV block (digoxin)
- Imaging – AXR, CXR, CT Head
- Iron and potassium tablets radio-opaque
- Aspiration pneumonia
- Head trauma
Decontamination:
- Skin (remove clothing + wash)
- GI tract
- Emesis with ipecac syrup (not used)
- Gastric lavage
- Activated charcoal:
- Adsorbs drugs and poisons
- Ratio of 10:1 charcoal to estimated weight of toxin
- Does not bind iron, potassium, lithium
- Binds cyanide and ethanol poorly
- Cathartics
- Antidotes
- Enhanced elimination via haemodialysis or urinary pH manipulation
| Drug | Pathophysiology | Tx/antidote |
| Paracetamol | >150- 200mg/kg in children and 7g in adults Sx: Initial – nausea, vomiting 24-36 hrs – elevated aminotransferase and hypoprothrombinaemiaSevere – liver failure, hepatic encephalopathy, renal failure, death Level >150-200mg/L at 4 hours post ingestion = risk of liver injury | Acetylcysteine (NAC) = glutathione substitute, binds toxic metabolite NAPQI-> commence within 8 hours of overdose |
| Amphetamines: Methamphetamine MDMA Cocaine Ephedrine | Sx: Euphoria, powerfulness, wakefulness Restlessness, agitation, acute psychosis Tachycardia, HTN, hyperthermia-> ARF, coagulopathy, brain damage, seizures Dilated pupils | Supportive therapy + benzodiazepines |
| Anticholinergic: Drugs Mushrooms | Antimuscarinic effects – “Red as a beet” skin flushed “Hot as a hare” hyperthermia “Dry as a bone” dry mucous membranes, anhidrosis “Blind as a bat” cycloplegia, blurred vision “Mad as a hatter” confusion, delirium Sinus tachycardia, dilated pupils Seizures s/o antihistamine or TCA Urinary retention | Supportive therapy BZP/ haloperidol IDC Physostigmine – useful in agitation, IV 0.5-1mg AE = bradycardia/seizures Avoid in suspected TCA due to cardiotoxicity |
| Antidepressants: TCA Monoamine oxidase inhibitor (MAO-I) | >1g is lethal TCA = Muscarinic antagonist (above) Alpha blockers (vasodilation) – hypotensive Na+ blockers (slow conduction, widened QRS and depressed cardiac contractility-> heart block, VT) Agitation, seizures Severe hypertension Interact with SSRI-> serotonin syndrome, agitation, muscle hyperactivity and hyperthermia | Supportive care May require ETT/ ventilation IVF +/- vasopressors (NE preferred) Sodium bicarbonate – bolus 50-100 mEq/L to increase extracellular sodium. Goal is to achieve serum alkalinization via sodium bicarbonate or hyperventilation/ avoiding apnoea. Do not use physostigmine – can aggravate cardiac depression |
| Antipsychotics | CNS depression Seizures Hypotension QT prolongation Dopamine blockers – parkinsonian movement disorders Neuroleptic malignant syndrome – lead pipe rigidity, hyperthermia, autonomic instability | |
| Aspirin (Salicylate) | >200mg/kg Causes uncoupling of oxidative phosphorylation and disruption of normal cellular metabolism Sx: Initially, hyperventilation = respiratory alkalosis HAGMA due to accumulation of lactate + renal bicarb excretion to compensate for respiratory alkalosis à Mixed respiratory alkalosis + metabolic acidosis HyperthermiaVomiting, dehydrationSeizures, coma, APO, CVS collapse | Supportive care – IVF Mild: Gut decontamination = lavage + charcoal Moderate: IV sodium bicarbonate = alkalinize urine and promote salicylate excretion (traps in ionized form) Severe: Haemodialysis |
| Beta blockers | Inhibit both beta 1 and 2 R at high doses (selectivity is lost) Propranolol is most toxic-> can cause sodium channel blocking effects + lipophilic (can enter CNS) Sx: Bradycardia, hypotension Cardiac conduction block/ seizures with propranolol | IVF Beta agonist Atropine Glucagon (omitted from most guidelines however) High dose insulin therapy ECMO |
| Calcium channel blockers | Depress SA node + slow AV node Reduce CO and BP | If extended release – may require bowel irrigation or charcoal IV calcium 2-10g (useful for depressed contractility). Adrenaline (positive inotrope)/ noradrenaline (vasoconstrictor) Glucagon + high dose insulin (manage hypotension) Lipid emulsion for severe verapamil overdose |
| Carbon Monoxide | Binds to Hb thus reducing oxygen delivery to tissues Sx: Headache, dizziness, vomiting, seizures, coma | 100% oxygen Consider hyperbaric oxygen |
| Cholinesterase inhibitors: Organophosphate Carbamate (insecticides) | Sx: Muscarinic + nicotinic effects Muscarinic – abdominal cramps, diarrhoea, sweating, salivation, urinary frequency and bronchial secretions Nicotinic –hypertension, tachy/bradycardia, muscle weakness, respiratory muscle paralysis, agitation/confusion, seizures Pneumonic “DUMBELS” Diarrhoea Urination Miosis, muscle weakness Bronchospasm Excitation Lacrimation Sweating, seizures, salivation Bloods acetylcholinesterase in RBC and butyryl cholinesterase in plasma ~ indirect estimate if synaptic cholinesterase activity | Atropine – muscarinic inhibitor. Doses are doubled every 3-4 minutes to achieve dried secretions and attain cardiac stability. Pralidoxime – 1g IV repeated every 3-4 hours, can restore cholinesterase activity at both M/N sites (used less nowadays) |
| Cyanide: Rodenticides Burning plastic/wool Ingestion of cassava/seeds | Binds to cytochrome oxidase, blocks cellular oxygen use-> hypoxia, lactic acidosis Sx: Headache, vomiting, syncope, seizures, coma Severe HAGMA Venous oxygen content high | Charcoal Supportive care Two antidotes: Nitrites-> induce methemoglobinemia (binds to cyanide) + thiosulfate (hastens conversion of cyanide to less toxic thiocyanate) Concentrated hydroxocobalamin (form vitamin B12) – converts cyanide to cyanocobalamin |
| Digoxin | Overdose or accumulation in setting of RF Sx: Vomiting, hyper/hypokalaemia, cardiac rhythm disturbances = sinus bradycardia, AV block, atrial tachycardia with block, junctional rhythm, PVC, VT | Atropine for bradycardia or AV block Digoxin Ab IV. Correct associated hyperkalaemia Adrenaline/ electrical pacing |
| Ethanol/ sedative- hypnotic drugs: BZP GHB | Euphoric, rowdy, stupor, coma Depression airway reflexes, aspiration Hypothermia | ETT if indicated IVF Flumazenil for BZP (however avoided, can precipitate seizures) |
| Opioids: Morphine Heroin Oxycodone Codeine | Coma, respiratory depression, miosis Strong tolerance and dependence Withdrawal within days – intense dysphoria, vomiting, muscle aches, lacrimation, rhinorrhea, diarrhoea, fever | Naloxone 0.4-2mg IV, 2-3 hour duration of action |
| Ethylene glycol/ methanol | Metabolism to highly toxic organic acids CNS depression, drunken state Severe Ma, renal failure, coma Blurred vision, blindness | Fomepizole – inhibits alcohol dehydrogenase enzyme = inhibits metabolism to toxic products. Ethanol (preferred) – difficult to monitor safe blood level given IV/PO/NG. |
| Rattlesnake envenomation | Venom contains destructive digestive enzymes Local effects around bite site Systemic = vomiting, muscle fasciculations, paraesthesia, metallic taste in mouth, shock, coagulopathy and thrombocytopaenia | Avoid unnecessary motion IV antivenin |
| Theophylline | Cause of activation not fully understood Sinus tachycardia, tremor, vomiting Hypotension, hypokalaemia, hypoglycaemia Cardiac arrhythmias Seizures | Gut decontamination Beta blocker (Esmolol) Phenobarbitone Haemodialysis |
| Cannabinoids: Marijuana (THC) | Euphoria, relaxation Hallucinations, psychosis in high doses Increased appetite | |
| Hallucinogens: LSD – lasts 6-12 hrs | Hallucinations, psychosis Dizziness, nausea Do not induce addiction or dependence Repetitive exposure leads to tolerance LSD – strong uterine contractions | |
| Alcohol | Alters several R functions – GABA A, Kir3/GIRK, adenosine reuptake, glycine, NMDA, 5-HT3 R Withdrawal = tremor, vomiting, sweating, agitation-> hallucination, seizures, delirium tremens | Supportive BZP for withdrawal |
| Psychedelics: Ketamine/PCP | Vivid dreams, hallucinations Hypertension, impaired memory |
Drug Abuse:
- Dependence = physical requirement
- Addiction = compulsive, relapsing drug use despite negative consequences
- Withdrawal = signs apparent after abused drug is no longer available
- Tolerance = escalation of dose to maintain effect
- All addictive drugs activate mesolimbic dopamine system
Chelating Agents
Drugs used to prevent or reverse toxic effects of a heavy metal on an enzyme or cellular target, or to accelerate metabolism
- Forms complex with heavy metal-> renders it unavailable for toxic interactions
- Examples:
- Dimercaprol/ succimer– antidote for arsenic
- Reverses arsenic induced inhibition of sulfhydryl containing enzymes
- Edetate calcium disodium
- Prevent depletion of calcium while metal intoxicated
- Unithiol – antidote for mercury and arsenic
- Penicillamine – antidote for copper
- Deferoxamine, Desferrioxamine, Prussian blue – antidote for iron
- Dimercaprol/ succimer– antidote for arsenic
Last Updated on September 24, 2021 by Andrew Crofton
Andrew Crofton
0
Tags :