Toxicology 4: Pathophysiology & Treatment of Poisoning Pathophysiology • Only limited no. of specific treatments & for poisoning of Poisoning • Understanding pathophysiology may lead to sensible treatment approaches Most Poisonings • Removal of available unabsorbed drug Managed by: • Enhancing elimination of from body • Supportive therapy to maintain vital body functions Treatment of Resuscitation & • Airway • Seizure control/prophylaxis Poisoning Supportive Care • Breathing • Metabolic stability Measures • Circulation • Fluids & electrolytes • Sedation • Renal function Limit Toxicity • Decrease absorption • Reverse toxic effects on cells & • Enhance elimination organs • Prevent • Prevent permanent cellular dmg biotransformation to more toxic substances First Aid • Most important aspect in acute poisoning is to provide appropriate first aid • Delivery of immediate resuscitation & first aid is crucial to prevent/reduce harm • ALWAYS TAKE PRIORITY in measures to support patient’s airways, breathing & circulation • NEVERE TAKE PRIORITY in attempts at decontamination (skin/GI) Action Plan Danger Send for Help Breathing Defibrillation Response Airway CPR Basic First Aid Oral Ingestion • Do NOT induce for Poisonings • In case of caustics/irritants, give small amount of water slowly to reduce severity of burns to mouth, throat & esophagus Contact with • Remove contaminated clothing Skin • Wash affected area thoroughly with cold/tepid water • Do not apply lotions/ointments/creams unless instructed to do so by Info Centre/after appropriate evaluation (if mild) Contact with • Irrigate eyes with gently running water/saline for 15 min OR 30 Eyes min for known corrosive agents • Do not instill drops/apply ointment • Seek medical advice Inhalation of • Remove person from exposure & place them in fresh air Poisons • Remove any obstruction to breathing • Perform CPR if necessary • Take care not to inhale expired air, which may be contaminated with toxic material (e.g. corrosives, cyanide) LIMIT TOXICITY Gastrointestinal Decontamination • To limit absorption of toxic substances from GI tract Induced • Rational: Empty stomach prevent absorption of toxins Emesis • NEVER give concentrated salt solution as it can be fatal • No Longer Recommended Routinely Serum of • Extract from ipecacuanha root Ipecac • Induces vomiting via central & peripheral routes Problems • Cause prolonged severe vomiting • Varying amount of toxin removed (Not very effective) • Must be given immediately (negligible amounts removed if given >1hr after ingestion) • More difficult administration of oral meds/ decontaminants (e.g. activated charcoal) • Result in pulmonary aspiration of vomit • Distract from resuscitation/supportive care priorities • Physical injuries secondary to vomiting (gastric perforation) CONTRAINDICATIONS • Seizures/↓Level of Consciousness (as risk of pulmonary aspiration) • Corrosive Ingestion (Risk of additional tissue dmg when irritant material is vomited) o E.g. Battery acid, drain cleaners, oven cleaners, automatic dishwasher tabs, HCl • Hydrocarbon ingestion (Major complication is aspiration (inhalation into lungs) that results in severe pulmonary toxicity o E.g. Kerosene, petrol, oil Gastric • Tube inserted into stomach via nose, where stomach is washed with Lavage harmless solvent (water/isotonic saline) • Should be done within 1 hr of ingestion • Unreliable removal of toxin • No proven benefit & not routine standard of care • Risk of pulmonary aspiration & mechanical injury to GI tract • Distraction from resuscitation & supportive care priorities Activated • Produced by super-heating distilled wood pulp = Results in fine porous Charcoal particles with enormous surface area • Network of tiny pores capable of trapping toxins (MW: 100-1000 g/mol) • Adsorbs most ingested toxins from GIT when admin. orally within 1hr • Give by oral/nasogastric tube as slurry (1 g/kg): Best given within 1 hr • Activated charcoal tablets available from pharmacy for flatulence (e.g. CharcoTabs) are NOT Effective & SHOULDN’T be USED • Most very small/highly charged molecules are poorly adsorbed to activated charcoal Agents Hydrocarbon • Ethanol • Ethylene glycol Poorly & • Isopropyl alcohol • Bound to • Lithium • Lead Activated Metals • Iron • Arsenic Charcoal • Potassium • Mercury Corrosives • Acids • Alkalis CONTRAINDICATIONS • If Initial Resuscitation is Incomplete • ↓Level of Consciousness/Delirium/Poor Cooperation (Risk of charcoal pulmonary aspiration) • Corrosive ingestion Whole • Aggressive & labor-intensive Bowel • Admin. large vol. of osmotically balanced polyethylene glycol Irrigation electrolyte sol. via nasogastric tube (2L/hr until clear effluent, up to 6 hrs). Rarely used but: Potentially useful for: • Iron overdose > 60 mg/kg • Slow release KCl ingestion >2.5 mmol/kg • Lead ingestion • Slow-release verapamil/diltiazem • Body packers Enhance Elimination • ↑Agent Removal Rate to ↓Duration & Severity of clinical intoxication Multiple-Dose • Repeated administration of oral activated charcoal progressively Activated fills entire gut lumen = ↑Drug Elimination Charcoal (MDAC) Achieves this by: • Interruption of entero-hepatic circulation o Effective if drug undergoes enterohepatic circulation & has small Vd) • GI Dialysis (Drug passes across gut mucosa from relatively high conc. in blood to low conc. in gut) o Only effective if drug is small, lipid-soluble, has small Vd & low protein binding • Can be used >1hr after ingestion • Adult: 50g/2hr or Child: 1 g/kg/2hr Useful • Coma from Carbamazepine/Phenobarbitone For: • Overdose from Dapsone/Quinine/Theophylline Urinary • Production of alkaline urine pH promotes ionization of acidic Alkalinisation drugs = Prevents absorption across renal tubular epithelium & promotes excretion in urine • Effective if drug filtered at glomerulus, has small Vd & is weak acid Potentially Salicylate • Weak acid Useful For Overdose • Treat with IV sodium bicarb (NOT 1st Line): Phenobarbitone • Weak acid Poisoning • Treat with IV sodium bicarb • Weak base Amphetamines • Treat with IV ammonium chloride Extracorporeal Hemodialysis • Process of removing toxins directly from blood Techniques using diffusion across semi-permeable membrane (“Artificial kidney”) • Toxin Properties: Small molecule, small Vd, high water solubility, low protein binding, rapid redistribution from tissue, slow endogenous elimination Useful • Toxic alcohol poisoning (methanol, For: ethylene glycol) • Poisoning from Theophylline/Salicylate • Lithium intoxication • Potassium salt overdose with life- threatening hyperkalemia • Metformin-induced lactic acidosis • Overdose from Valproate/Carbamazepine • Coma from Phenobarbitone Hemoperfusion • Rarely used • Process of removing toxins by crossing blood across bed of adsorbent material (e.g. activated charcoal) • Toxin Properties same as hemodialysis except protein binding • Carbamazepine, phenobarbital, phenytoin, theophylline Plasmapheresis Exchange Transfusion