Drug Overdose

Approach to Acute Poisoning 
  • Resuscitation 
    1. Airway 
    2. Breathing 
    3. Circulation 
    4. Seizure control 
    5. Correct hypoglycemia 
    6. Correct hyperthermia 
    7. Resuscitation antidotes 
    8. Risk assessment 
  • Investigations 
  • Supportive care and monitoring 
  • Decontamination with activated charcoal. It should be given within 1 hour. 
  • Enhanced elimination: 
    • Multiple dose charcoal in quinine, carbamazepine, theophylline and barbiturate poisoning 
    • Whole bowel irrigation with golytely 
    • Urinary alkalinization: Alkaline urinary Ph promotes ionization of acidic drugs, prevents absorption and enhances elimination. Eg: Salicylates, Phenobarbitone. Regularly dipstick urine and aim for urinary pH>7.5. 
    • Hemodialysis for Lithium, Pradaxa, Salicylates, metformin lactic acidosis, phenobarbitone, toxic alcohols and valproic acid. 
    • Exchange transfusion in methemoglobinemia 
Specific Antidotes 
  • Amphetamines -> Benzodiazepines + consider dantrolene 
  • Anticholinergics -> Physostigmine (Cholinesterase inhibitor ) 
  • Benzodiazepines -> Flumazenil 
  • Beta-blockers –> High-dose Insulin Euglycemic Therapy + Adrenaline + ?glucagon 
  • Haloperidol -> Benztropine 
  • Calcium channel blockers -> IV calcium, High-dose Insulin Euglycemic Therapy + ?Glucagon 
  • Cholinergics (Organophosphates) -> Atropine, Pralidoxime 
  • Cyanide -> Hydroxocobalamin + Sodium thiosulphate + Sodium Nitrate 
  • Digoxin -> Digibind (Fab), Mg2+ 
  • Ethylene glycol -> Ethanol, 4-methylpyrazole, Pyridoxine, Thiamine 
  • Heparin -> Protamine 
  • Hypoglycemia -> Dextrose; octreotide (if oral hypoglycemic agent) 
  • Iron -> Desferrioxamine 
  • Isoniazid -> Pyridoxine 
  • Lead -> Dimercaprol, BAL 
  • Malignant hyperthermia -> Dantrolene 
  • Methanol -> Ethanol, 4-methylpyrazole, Folate 
  • Methaemaglobinaemia -> Methylene Blue, Ascorbic Acid 
  • Methotrexate -> Folinic acid 
  • Neuroleptic malignant syndrome -> Bromocriptine, Amantadine, Dantrolene 
  • Opioids -> Naloxone 
  • Paracetamol -> N-acetylcysteine
  • Sodium channel blockers -> NaHCO3 
  • Serotonin syndrome -> Cyproheptadine, Olanzepine, Benzodiazepines 
  • Sympathomimetics -> Adrenegic blockers (avoid beta blockers) 
  • Tricyclic overdose –> NaHCO3 
  • Warfarin -> Vitamin K, FFP, Prothrombin complex 
Acetaminophen Overdose: 
  1. Causes depletion of glutathione levels and causes liver death.  
  2. Treat with activated charcoal in 4 hours and NAC, regardless of drug levels. Adverse effects of NAC include bronchospasm, hypotension and angioedema. 
  3. Drug levels, Ammonia, INR, bilirubin, AST/ALT levels should be monitored closely 
  4. High-risk features mandating admission to a liver transplant centre are: 
    • INR >3.0 at 48 hours or >4.5 at any time 
    • Oliguria or creatinine > 200 micromol/L 
    • Acidosis with pH < 7.3 after resuscitation 
    • Systolic hypotension with BP < 80mmHg 
    • Hypoglycemia 
    • Severe thrombocytopenia 
    • Encephalopathy of any degree 
    • Lactic acidosis? 
Beta-Blocker Overdose 
Two beta-blockers require special consideration: 
  1. propanolol -> causes sodium channel blockade -> QRS widening -> treat with NaHCO3 
  2. Sotalol -> causes potassium efflux blockade -> long QT -> monitor for Torsades 
Can cause bronchospasm, bradycardia, hypotension, AV block, hypoglycemia, hyperkalemia 
Treatment includes pacing/Isoproterenol, vasopressors, NaHCO3, beta agonists and correcting electrolytes. 
Cocaine Toxicity: 
If ACS, give aspirin, nitrates, BZD and calcium channel blockers. Don’t give pure beta blockers due to potential unopposed alpha action. 
Corrosive acids: 
  • Rinse the mouth with water as an immediate first aid measure. 
  • do not induce vomiting 
  • do not administer oral fluids 
  • do not administer activated charcoal 
  • do not attempt pH neutralization 
  • do not perform gastric lavage or insert an nasogastric tube (until endoscopy is performed) 
Digoxin Toxicity: 
  • CVS: sinus bradycardia, AF, atrial flutter, AF with AV block, conduction dysfunction, ventricular ectopic beats, every arrhythmia except sinus tachycardia. 
  • GI: anorexia, nausea, vomiting, diarrhea, abdominal pain 
  • CNS: lethargy, confusion, weakness, headache, delirium, psychosis, photophobia, blurred vision,  coloured halo’s around lights 
  • Metabolic: hyperkalemia 
Opiate Overdose: 
  • Naloxone: titrated doses until reversal of respiratory depression -> may require an infusion. Opiate levels don’t correlate with the required naloxone dose. 
  • dose: 0.4-2mg IV/IM/SC -> 1-10mcg/kg/hr 
Opiate withdrawal: 
Can manifest as restlessness, lacrimation, sweating and diarrhea. Treat with clonidine and methadone 
Tricyclic Antidepressant Toxicity 
  1. profound alpha-adrenergic blockade 
  2. Anticholinergic effects ( M block) 
  3. inhibition of catecholamine reuptake (initial increase in sympathetic tone -> prolonged decrease) 
  4. sodium channel blockade -> cardiotoxicity and CNS effects 
Can manifest as dry mucous membranes, tachycardia, hypertension, nystagmus, dizziness, unconscious/coma, seizures, increase in tone, hyperreflexia, pupillary dilation, blurred vision, dry mouth, ileus, metabolic acidosis, and urinary retention.  
Treatment is with NaHCO3 and hyperventilation to keep Ph>7.5. Increasing the serum pH with bicarbonate -> increases the proportion of non-ionised drug which will increase the drug distribution throughout rest of body and away from heart. 
Neuroleptic Malignant syndrome: 
Due to dopamine receptor blockade and Caused by drugs such as Haldol, Risperidone, Phenothiazines like chlorpromazine, olanzapine, metoclopramide and abrupt ceasing of parkinson’s drugs. It develops over 24-72 hrs to weeks and manifests as hyperthermia, lead pipe rigidity, dysarthria, parkinsonism, chorea, trismus, hyporeflexia, stupor / mutism, GTC seizures, coma, tachycardia, high BP, autonomic dysfunction, rhabdomyolysis, AKI, tachypnea, and agitation. Other findings include elevated CPK, leukocytosis, and mild elevation of LDH.  (It doesn’t cause hyperreflexia, clonus, sudden onset, agitation and diarrhea, which differentiates it from serotonin toxicity).   
Differential diagnoses include Serotonin syndrome, malignant hyperthermia, Anticholinergic toxicity (normal tone and reflexes), acute Baclofen withdrawal (raised temperature, autonomic instability and muscle spasms and rigidity with raised CPK), sedative-hypnotic withdrawal and sympathomimetic toxicity. 
Treatment is mainly supportive and includes cardiopulmonary stabilization, cooling blankets, IVF, BZD for agitation, Bromocriptine( dopamine agonist is used to restore lost dopaminergic tone) and Amantadine ( dopaminergic and anticholinergic), Dantrolene ( skeletal muscle relaxant) for rigidity, and Non depolarizing neuromuscular blockers for extreme rigidity.
Serotonin Syndrome: 
Onset is within 24 hours and caused by SSRI, TCA like amitryptiline and MAO inhibitors. Eg: Citalopram, Opiates like fentanyl and tramadol, Ecstasy, MDMA, LSA, amphetamines, lithium, and linezolid. 
Serotonin syndrome results from drug-induced over-stimulation of serotonin receptors in the CNS and is characterized by a triad of CNS dysfunction, autonomic disturbance and neuromuscular hyperactivity.  
Clinical manifestations include fever, rigidity, hyperreflexia, either spontaneous or inducible myoclonus, ocular clonus, bilateral babinski sign, incoordination, ataxia, dilated pupils, confusion, seizures, coma, agitation, restlessness, tachypnea, tachycardia, QT prolongation, hypotension/hypertension, flushing, renal failure and DIC.  
Treatment includes seizure control, intubation if needed for airway protection, cardiopulmonary support, BZD as first choice medications and antidotes includes 5-HT antagonists like cyproheptadine or olanzapine. Usually resolves in 24 hours unless long acting SSRI is used. 
Malignant hyperthermia: 
Caused by exposure certain inhaled anesthetics like halothane, resulting in excess Ca2+ release during muscle contraction. This will lead to prolonged and intensified interaction between actin and myosin, resulting in increased muscle metabolism + heat production, enhanced aerobic metabolism with CO2 production and lactic acidosis. 
Clinical findings include fever, rigidity, decreased reflexes, agitation, tachypnea, tachycardia, hypertension, autonomic instability, hyperkalemia, myoglobinuria and increased ETCo2 which doesn’t normalize with increased ventilation. 
Treatment includes supportive care, Dantrolene for rigidity, HCO3 for severe acidosis and muscle relaxation with non depolarizing neuromuscular blockers. 

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