1. OVERDOSE & TOXIC INGESTIONS

2. What is an Overdose? Exposure to excessive amounts of a substance normally intended for consumption. Poisoning is the development of harmful effects following exposure to chemicals. Pharmaceuticals are responsible for 41% of poisonings and 75% of fatal poisonings.

3. Treatment Overview Supportive Care Prevention of toxin absorption Enhancement of drug elimination Administration of antidote

4. Initial Measures Airway Airway –Establish patent airway by positioning and suctioning. –Intubate if obtunded, comatose, no gag reflex. Breathing Breathing –Assess depth and rate. –Pulse ox in all. –ABG if suspicious.

5. Initial Measures Circulation –Treat with NS or pressors if hypotensive –Assess for arrhythmias -D-Drugs (give all three) -D-Drugs (give all three) Dextrose 50%, Dextrose 50%, Thiamine 100mg. Thiamine 100mg. Naloxone0.4 to 2mg & Naloxone0.4 to 2mg & consider Flumazenil consider Flumazenil (do not give flumazenil in TCA overdose, BZD dependency and seizure disorder)

6. Prevention of Toxin Absorption Emesis: -Now not performed. Replaced by lavage/charcoal -Contraindicated in corrosive poisonings/aspiration risk. Gastric Lavage: Indications: Indications: - Removal of gastric contents (within the first hour). Examination of gastric contents. Facilitate charcoal. Contraindications: Contraindications: - Do not do if patient comatose unless intubated. Also do not use if corrosives are ingested. (controversial) Technique: Technique: - Place patient in left lateral head down position if not intubated. Insert a soft lubricated tube through mouth or nose into stomach. Aspirate and save contents and then lavage repeatedly with 50-100ml of fluid until returns are clear.Use luke warm water or saline.

7. Prevention of Toxin Absorption Activated Charcoal –Adsorbs almost all drugs and poisons. Poorly adsorbed substances are Lithium, Potassium, alcohol, iron, cyanide. Indications: All poisonings. All poisonings.Contraindications: Comatose or obtunded unless given by gastric tube or intubated as drinking charcoal can cause emesis.Comatose or obtunded unless given by gastric tube or intubated as drinking charcoal can cause emesis. Ileus or intestinal obstruction. (delays expulsion of charcoal) Ileus or intestinal obstruction. (delays expulsion of charcoal) Corrosive poisonings where endoscopy is planned. Corrosive poisonings where endoscopy is planned.Technique: 60-100grams orally or via gastric tube.Repeat doses 20-30mg every 3-4 hours may be used to hasten the elimination of some drugs (digoxin, theophylline and phenobarbitol) by adsorbing drug excreted into the gut lumen (entero hepatic circulation). 60-100grams orally or via gastric tube.Repeat doses 20-30mg every 3-4 hours may be used to hasten the elimination of some drugs (digoxin, theophylline and phenobarbitol) by adsorbing drug excreted into the gut lumen (entero hepatic circulation).

8. Prevention of Toxin Absorption Whole Bowel Irrigation: Cleanses the GI tract Indications: -Used for “body stuffers/packers” (People who swallow packets of drugs for smuggling.) -Used for “body stuffers/packers” (People who swallow packets of drugs for smuggling.) - Massive iron ingestion - Massive iron ingestionTechnique: 2 Liters/hour of go-lytely electrolyte soln. Given via gastric tube at rate of 1- 2L/hour until rectal effluent is clear. Patient must be able to sit to pass contents. 2 Liters/hour of go-lytely electrolyte soln. Given via gastric tube at rate of 1- 2L/hour until rectal effluent is clear. Patient must be able to sit to pass contents.

9. Increased drug removal  Urinary manipulation Alkalization of urine: Salicylates, Phenobarbitol. Alkalization of urine: Salicylates, Phenobarbitol. Forced diuresis: No longer recommended as it causes electrolyte imbalances. Forced diuresis: No longer recommended as it causes electrolyte imbalances.  Dialysis  Known dialyzable drugs.  Severe states :coma, refractory hypotension, hypothermia for quick effect  Hepatic or renal failure where excretion of the drug may be compromised.

10. Diagnosis of Overdose History: Dependent upon history obtained and reliability of history. Paramedics/Police will usually bring in pill bottles: Calculate the amount taken, and always assume the worst case scenario.

11. Diagnosis of Overdose Physical examination 5P’s :Pressure, Pulse rate, perspiration, pupils peristalsis. Based on above three syndromes: Sympathomimetic syndrome : Amphetamines, cocaine, ephedrine, psuedoephidrine, PCP (pupils may be small) Amphetamines, cocaine, ephedrine, psuedoephidrine, PCP (pupils may be small) Sympatholytic syndrome: Benzo, Barbiturates, other sedative hypnotics, opioids, clonidine. Benzo, Barbiturates, other sedative hypnotics, opioids, clonidine.Cholinergic: Nicotine, organophosphates, physostigmine. Nicotine, organophosphates, physostigmine.

12. Initial Laboratory Evaluation EKG Basic Chemistry –Calculate anion gap ABGABG Drug Screen Serum Osmolality (calculate osmolar gap) Quantitative Drug Levels

13. Acetaminophen Pathophysiology Acetaminophen is metabolized by the cytochrome P450 pathway to a toxic intermediate that is detoxified by glutathione. With acute acetaminophen overdose hepatocellular glutathione is depleted allowing the toxic intermediate to attack cell proteins and cause cell necrosis. Patients with enhanced cytochrome P450 activity like alcoholics and anticonvulsant users are at greater risk of hepatotoxicity. Acetaminophen is metabolized by the cytochrome P450 pathway to a toxic intermediate that is detoxified by glutathione. With acute acetaminophen overdose hepatocellular glutathione is depleted allowing the toxic intermediate to attack cell proteins and cause cell necrosis. Patients with enhanced cytochrome P450 activity like alcoholics and anticonvulsant users are at greater risk of hepatotoxicity.

14. Acetaminophen Dose: Acute ingestion: >7.5 grams/24 hours is toxic – just a guideline! Chronic ingestion: >4 grams a day. Symptoms: 1 st 24 hours to 48 hours-Asymptomatic. 1 st 24 hours to 48 hours-Asymptomatic. 24-48 hours – Rise of aminotransfersases, jaundice, encephalopathy. 24-48 hours – Rise of aminotransfersases, jaundice, encephalopathy.Treatment: Lavage & Activated Charcoal indicated. Rumack-Matthew Nomogram utilized to decide whether treatment with N-acetylcysteine is required.

16. Acetaminophen N-Acetylcysteine increases the availability of glutathione, decreasing hepatic toxicity. If patient has a toxic level, give the full course (usually 17 doses). 140mg/kg orally followed by 70mg/kg. May be helpful even up to 36 hours after ingestion If uncertain about the timing of ingestion and at high risk patients (alcoholics, CytP450 inducing drug takers, liver disease) use lower line. Remember: Nomogram not useful for chronic overdoses and for overdoses that may be associated with ingestion of another drug that delays GI motility.

17. The Alcohols Methanol Found in windshield wipers.Methanol is metabolized to formaldehyde and formic acid which acts as toxin. Symptoms may not appear for 12-18 hours because toxins must accumulate, may be longer if ingested with ethanol because EtOH inhibits metabolism Symptoms: CNS depression, visual changes with blurring/blindness, abdominal pain, N/V Labs: Wide anion gap metabolic acidosis with osmolar gap >10

18. The Alcohols Ethylene Glycol Found in antifreeze. 3 distinct clinical phases due to the toxic metabolites glycolate, glyoxalate, and oxalate –First 12 hours: CNS effects appears intoxicated –12-24 hours: Cardiopulmonary effects Increased HR, RR and BP CHF, respiratory distress syndrome, circulatory collapse –24-72 hours: Renal effects ATN with ARF Wide anion gap metabolic acidosis with osmolar gap >10 Metabolized to oxalic acid. Calcium oxalate crystals seen in urine 33% of the time

19. The Alcohols Ethylene Glycol Oxalate crystals

20. The Alcohols Treatment of Methanol and Ethylene Glycol Ingestion Rapid Diagnosis –Hx suspicious for use –Wide anion gap with a wide osmolar gap, then order serum level and begin: Ethanol infusion (not used as much) to keep blood alcohol >100. Ethanol infusion (not used as much) to keep blood alcohol >100. –Competitively inhibits metabolism of MeOH and EG by alcohol dehydrogenase, has a 10-20 greater affinity than MeOH and 100 times that of EG –Is continued until measured levels are zero Fomepizole (4-methylpyrazole) – more common Fomepizole (4-methylpyrazole) – more common –A competitive inhibitor of alcohol dehydrogenase –Is an alternative to EtOH infusion. D ialysis for severe cases (serum level > 50mg/dl, refractory acidosis)

21. The Alcohols Isopropyl Alcohol Found in rubbing alcohol and paint thinners CNS effects are twice as potent and twice as long acting as EtOH Symptoms are similar to EtOH intoxication, severe posioning causes early onset coma, respiratory depression, and hypotension Hemorrhagic gastritis is a characteristic finding Ketosis without acidosis –Metabolized to acetone –Ketonemia/ketonuria and osmolol gap with minimal or no acidosis is unique characteristic Treatment is supportive with dialysis if patient continues to deteriorate.

22. Tricyclic Antidepressants Most dangerous of overdoses. (25% of fatalities occur in patients who are awake, alert, and in NSR at time of presentation) Clinical findings & Treatments (1) Anticholinergic: Tachycardia, dry mouth, flushed skin, decreased peristalsis. Tachycardia, dry mouth, flushed skin, decreased peristalsis. (2) Cardiotoxicity: Quinidine like effect. Blocks sodium channels. Therefore widening of the QRS interval, ventricular arrhythmias, AV nodal block. Quinidine like effect. Blocks sodium channels. Therefore widening of the QRS interval, ventricular arrhythmias, AV nodal block.

23. Tricyclic Antidepressants Rx: Rx:  Admit in Telemetry.  Alkalinization either using sodium bicarbonate and hyperventilation if intubated to a pH of 7.45-7.55. The sodium in the NaHCO3 alleviates depression of the sodium channels. Also acidosis impairs sodium channels so alkalinization beneficial.  Manage arrhythmias with lidocaine, magnesium, isoproterenol, and pacing Neurologic: Neurologic: Seizures. ( Note due to absence of sweating and seizures hyperthermia can occur) Seizures. ( Note due to absence of sweating and seizures hyperthermia can occur) Rx: benzodiazepines. Rx: benzodiazepines.

24. Salicylates Aspirin, methyl salicylate (various OTC drugs) Pathophysiology:  Uncouple cellular oxidative phosphorylation and cause anaerobic metabolism (lactic acidosis) and heat production.  Salicylates directly stimulate respiratory centers in the brainstem.  Mixed respiratory alkalosis with metabolic acidosis. (wide anion gap).  Coagulopathy present secondary to platelet dysfunction and decreased synthesis of coagulation factors (salicylate induced hypoprothrombinemia).

25. Salicylates Symptoms: Dose dependant acute ingestion (> 200mg/kg) or chronic excessive dosing. acute ingestion (> 200mg/kg) or chronic excessive dosing. Severe: Agitation, Coma, CV collapse, pulmonary edema, hyperthermia & pulmonary edema, hyperthermia & death. death. Labs: Labs: Suspect in any anion gap metabolic acidosis Suspect in any anion gap metabolic acidosis Salicylate level elevated salicylate level. Salicylate level elevated salicylate level. ABG : Shows mixed Met acidosis & resp alkalosis. ABG : Shows mixed Met acidosis & resp alkalosis.

26. Salicylates Therapy: General: General: Activated charcoal( 10:1 by weight). Activated charcoal( 10:1 by weight). NaHCO3: Critical for therapy as acidosis promotes the entry of salicylic acid into the cells. (keep>7.4). NaHCO3: Critical for therapy as acidosis promotes the entry of salicylic acid into the cells. (keep>7.4).Specific: Urinary alkalization. Hemodialysis ( >1000-2000mg/L after acute overdose or> 60-70mg/dl with sub acute or chronic overdose).

27. Beta Blockers Most toxic is Propranolol Symptoms: Cardiac: Bradycardia, AV blockade, hypotension. Cardiac: Bradycardia, AV blockade, hypotension. Rx: Atropine or Isoproterenol if no Rx: Atropine or Isoproterenol if no response give Glucagon. May need response give Glucagon. May need temporary pacing. temporary pacing. CNS: Delerium, coma, or seizures. CNS: Delerium, coma, or seizures. Rx:Ativan for seizures Rx:Ativan for seizures Electrolyte: Hyperkalemia and hypoglycemia Electrolyte: Hyperkalemia and hypoglycemia

28. Ca Channel Blockers Symptoms include bradycardia, conduction delays, impaired contractility, and hypotension Gastric lavage and activated charcoal –May consider whole bowel irrigation for sustained release preparations May respond to atropine, isoproterenol, or pacing IVF If no response IV calcium chloride or calcium gluconate to treat hypotension and conduction defects. Glucagon is occasionally beneficial in severe toxicity

29. Digitalis Pathophysiology: 2 main effects: Blocks AV node & blocks Na/K ATPase. The blockade of Na/K ATPase increases intracellular Ca and causes delayed after depolarizations (which can cause VPC and VT). Toxic: Therapeutic ratio is very narrow. Acute overdose: GI: Nausea, vomiting. Cardiac: Bradycardia, cardiac arrhythmias mostly ventricular. Cardiac: Bradycardia, cardiac arrhythmias mostly ventricular. Electrolyte: Hyperkalemia. Electrolyte: Hyperkalemia. Chronic: Hypokalemia, hypomagnesemia as patients are on diuretics. Hypokalemia aggravates dig toxicity. Treatment: Bradycardia can be controlled with atropine or temporary pacing Lidocaine for ventricular arrhythmias Digibind (digoxin-specific Fab antibody fragments) is effective in rapidly reversing life- threatening intoxications –Is cleared via renal excretion –40 mg vial neutralizes ~0.6 mg of digoxin

30. Atropine & Anticholinergics Drugs with anticholinergic effects:  Atropine  Antihistamines: Benadryl  Mushrooms  TCA Effects: Symptoms: Dry mouth, thirst, blurring of vision, constipation. Signs: Psychosis, dilated pupils, fever, ileus, urinary retention. Rx: Charcoal (can give late as there is delayed gut emptying) Physostigmine (with ECG monitoring).

31. Cyanide Situations:  Fires-HCN gas is a component of smoke in fires  Apricot pits  Nitroprusside infusion  Acetonitrile (finger nail glue removers) has CN Pathophysiology: Rapidly absorbed by any route (GI, skin, inhalation) Rapidly absorbed by any route (GI, skin, inhalation) Inhibits cytochrome oxidase, cellular respiration. Switches to anaerobic metabolism and therefore lactic acidosis occurs. Inhibits cytochrome oxidase, cellular respiration. Switches to anaerobic metabolism and therefore lactic acidosis occurs.

32. Cyanide Symptoms: Headache, dizzinness, abdominal pain, nausea. Followed quickly by syncope, shock and coma. Headache, dizzinness, abdominal pain, nausea. Followed quickly by syncope, shock and coma.Labs: Unexplained lactic acidosis Unexplained lactic acidosis High Venous O2 sats (>90%) as tissues fail to take up oxygen. High Venous O2 sats (>90%) as tissues fail to take up oxygen.Treatment:  Remove from site of exposure  Charcoal: CN is poorly adsorbed,therefore larger doses.  “Pack” available consists of Amylnitrite, Sodium nitrite and Na thiosulfate.

33. Overview of Antidotes DrugAntidote AcetaminophenN-Acetylcysteine Organophosphates Atropine/Pralidoxim e OpioidsNaloxone BenzodiazepinesFlumazanil Ethylene Glycol Fomepizol MethanolFomepizol