1/11/2019 Objectives ◼ Drugs of abuse ◼ Lithium ◼ Benzodiazepines ◼ Heavy metals ◼ Barbiturates ◼ Cyanide/Hydrogen sulfate ◼ Hallucinogens Toxicology Review ◼ Organophosphates ◼ Cocaine ◼ ◼ Amphetamines Local anesthetics ◼ Narcotics ◼ Mushrooms David Donaldson, D.O. ◼ Rave drugs ◼ Plants Emergency Medicine ◼ Isoniazid William Beaumont Hospital ◼ Hypoglycemics ◼ Inhalation toxins ◼ Biologic hazards 1 2 Benzodiazepines ◼ Stimulation of the benzodiazepine receptor ◼ Increases the sensitivity of the GABA receptor complex ◼ Leads to inhibitory effects ◼ Lipid soluble 3 4 Clinical Features Treatment ◼ CNS ◼ Activated charcoal ◼ Drowsiness ◼ Elimination enhancement ◼ Dizziness ◼ Not effective ◼ Slurred speech ◼ Respiratory support ◼ Confusion ◼ Ataxia ◼ Paradoxical reactions ◼ Respiratory depression 5 6 1 1/11/2019 Flumazenil ◼ Selective antagonist ◼ 0.2mg IV q minute (total of 3mg) ◼ Seizure Activity ◼ Co-ingestions ◼ Physically dependent on Benzodiazepines ◼ History of seizures 7 8 Barbiturates Barbiturates ◼ Lipid soluble ◼ Pharmacology ◼ Mimics ETOH intoxication ◼ Enhances the action of GABA receptors ◼ Lack of coordination ◼ Inhibits noradrenergic excitation at neuronal junctions ◼ Slurred speech ◼ Impaired thinking ◼ Skin bullae ◼ 6% 9 10 Barbiturates Treatment ◼ Mortality ◼ Airway ◼ Early ◼ Activated charcoal ◼ Cardiovascular ◼ Multi-dose ◼ Late ◼ Fluid support ◼ Pulmonary ◼ Alkalinization of urine ◼ Increases the excretion rate (5 to 10 fold) ◼ Hemodialysis ◼ 6 to 9 times more effective than alkalinization 11 12 2 1/11/2019 Hallucinogens ◼ PCP ◼ Dissociative anesthetic with brainstem preservation ◼ Nystagmus, agitation, ataxia ◼ Muscle rigidity, seizure, coma, rhabdo, hyperpyrexia ◼ LSD ◼ Affects serotonergic and dopaminergic pathways ◼ Paranoia, anxiety, psychosis ◼ Marijuana ◼ Mushrooms ◼ Psilocybin ◼ LSD-like ◼ Mescaline ◼ Similar to amphetamines 13 14 Cocaine ◼ Onset ◼ 30 sec to 2 minutes ◼ Peak Effect ◼ 30 minutes ◼ Duration ◼ 1 to 3 hours 15 16 Cocaine (Pathophysiology) Clinical Features ◼ Local Anesthetic ◼ Cardiac ◼ Inhibits conduction of nerve impulses by sodium channel blockade ◼ Arrhythmias ◼ CNS Stimulant ◼ Myocarditis ◼ Blocks presynaptic reuptake of norepinephrine, dopamine, and serotonin ◼ Cardiomyopathy ◼ Cardiac ◼ Aortic dissection ◼ Sodium channel blockade ◼ Coronary artery dissection ◼ QRS widening ◼ Accelerated atherosclerosis ◼ QT prolongation 17 18 3 1/11/2019 Clinical Features Clinical Features ◼ CNS ◼ Pulmonary ◼ Hemorrhage ◼ Seizures ◼ Edema ◼ Intracranial infarction and hemorrhages ◼ Pneumomediastinum and pneumothorax ◼ Renal ◼ GI ◼ Body stuffers ◼ Rhabdomyolysis ◼ Body packers ◼ Obstetrics ◼ Uteroplacental blood flow decreased 19 20 Treatment ◼ Sedation ◼ Benzodiazepines ◼ Fluid resuscitation ◼ Cooling ◼ Whole bowel lavage ◼ Wide complex tachyarrhythmia ◼ Sodium bicarb ◼ Beta-blockers (contraindicated) ◼ Unopposed alpha-adrenergic receptor stimulation 21 22 Amphetamines Treatment ◼ Competitively inhibit the reuptake of ◼ Cardiac monitoring neurotransmitters ◼ Benzodiazepines ◼ Inhibit monoamine oxidase ◼ Avoid beta-blockers ◼ Inhibit the breakdown of catecholamines 23 24 4 1/11/2019 Narcotics ◼ Overdose ◼ Pinpoint pupils ◼ Midrange/dilated if CNS hypoxia ◼ Hypoventilation ◼ Pulmonary edema 25 26 Narcotics Narcotics ◼ Heroin ◼ Acute Intoxication ◼ 20 to 200:1 ratio of adulteration ◼ Quinine ◼ Drowsiness ◼ Lactose ◼ Euphoria ◼ Sucrose ◼ Heroin ◼ Talc ◼ Methadone ◼ Miosis ◼ Mannitol ◼ Baking soda ◼ Morphine ◼ Slowed respirations ◼ Codeine ◼ Nausea and vomiting ◼ Meperidine ◼ Pruritus ◼ Hydromorphone ◼ Oxycodone 27 28 Narcotics Narcotic Withdrawal ◼ Withdrawal ◼ Heroin ◼ 12-14 hours after last dose ◼ Piloerection ◼ Sweating ◼ Methadone ◼ Lacrimation ◼ Myalgia ◼ 24-36 hours after last dose ◼ Yawning ◼ Abdominal cramping ◼ Not life threatening ◼ Methadone ◼ Rhinorrhea and vomiting ◼ Clonidine ◼ Irritable and confused ◼ Inhibiting adrenergic activity at alpha-2 adrenergic receptors 29 30 5 1/11/2019 Treatment ◼ Naloxone ◼ Antagonizes opiate receptor sites in the CNS ◼ Serum half-life is one hour (duration 2-3 hours) ◼ 2.0mg in adults ◼ 0.01mg/kg in children ◼ May be given: ◼ Subcutaneously ◼ Intratracheally ◼ Intramuscular ◼ Intravenously 31 32 GHB CNS Effects ◼ Gamma-hydroxybutyric acid ◼ Binds to GABA-B receptors in the brain ◼ Similar in structure to GABA ◼ Inhibits noradrenaline release in the ◼ Maximal plasma concentration hypothalamus ◼ 20-30 minutes ◼ Mediates release of an opiate-like substance in ◼ Half-life 27 minutes the brain 33 34 GHB Treatment ◼ Oral Dose ◼ Airway support ◼ 10mg/kg ◼ Cardiac monitoring ◼ Amnesia and hypotonia ◼ Reversal of GHB ◼ 20-30mg/kg ◼ Physostigmine ◼ Drowsiness and sleep ◼ Reverse sedation in clinical trials ◼ 50-70mg/kg ◼ Risks ◼ Deep coma ◼ Bradycardia ◼ Usually lasts 3-6 hours ◼ Asystole ◼ Accompanied by myoclonic jerks and agitation ◼ Seizures 35 36 6 1/11/2019 MDMA (Ecstasy) Treatment ◼ Amphetamine derivative ◼ Supportive care ◼ Catecholamine release from presynaptic vesicles ◼ Cooling ◼ Sympathomimetic effects ◼ Seizures ◼ Massive release of serotonin ◼ Benzodiazepines 37 38 Ketamine ◼ Structurally similar to PCP ◼ Dissociative anesthetic with brainstem preservation ◼ Nystagmus, agitation, ataxia ◼ Muscle rigidity, seizure, coma, rhabdo, hyperpyrexia ◼ Used as a dissociative anesthetic ◼ “Special K” 39 40 Pathophysiology Clinical Effects ◼ Competes with other similar-molecular-weight ◼ GI symptoms ◼ Cardiovascular ions resulting in displacement ◼ Prolonged QT ◼ Bradycardia ◼ Sodium ◼ Renal ◼ Potassium ◼ polyuria ◼ CNS ◼ Magnesium ◼ Tremor ◼ Memory loss ◼ Calcium ◼ Weakness ◼ ◼ Ataxia Decreases in intracellular cAMP ◼ Seizures ◼ Interferes with the release and reuptake of ◼ Serum levels do not predict CNS levels norepinphrine 41 42 7 1/11/2019 Treatment ◼ Activated charcoal is ineffective ◼ Whole-bowel irrigation ◼ Aggressive hydration ◼ Hemodialysis ◼ Levels > 3.5 mEq/L (>4.0 in an acute ingestion) ◼ Coma, seizures, CV collapse, renal failure ◼ Little or no change in levels after 6 hours of hydration ◼ Levels > 1.0 after 36 hours of treatment 43 44 Lead Lead ◼ CNS ◼ Combination of abdominal or neurologic ◼ Damage to the microvascular system dysfunction with hemolytic anemia=lead toxicity ◼ Disruption of the blood-brain barrier ◼ Anemia and basophilic stippling ◼ Cerebral edema ◼ Seizures ◼ PbB level > 10 microgram/dL ◼ Kidney ◼ X-ray ◼ Affects the proximal tubule ◼ Toxic hepatitis ◼ Treatment ◼ Whole bowel irrigation ◼ Clinical features ◼ Chelation therapy BAL ◼ Encephalopathy, seizures, parathesias, abdominal pain, EDTA peripheral neuropathy (“classic”=wrist drop) DMSA 45 46 Arsenic Iron ◼ Severe gastroenteritis, muscle twitches, delirium, ◼ Toxic dose 30-40 mg (elemental)/kg hepatic/renal failure ◼ 0-6 hours Gastro, dehydration ◼ 6-48 hours quiescent phase ◼ Diagnosis: 24 hour urine ◼ 12-48 hours acidosis, coma, hepatic ◼ Treatment: chelation (BAL) ◼ 2-6 weeks recovery, scaring ◼ Serum Fe level (TIBC not reliable) ◼ Charcoal doesn’t bind ◼ X-ray ◼ Treatment = whole-bowel irrigation and chelating agent (deferoxamine) 47 48 8 1/11/2019 Mercury ◼ Interferes with enzyme activity ◼ CNS, GI, renal toxicity ◼ Metallic mercury: benign if ingested but very dangerous is inhaled or injected ◼ Diagnosis: 24 hour urine ◼ Treatment: lavage and chelation (BAL) 49 50 Cyanide Hydrogen Sulfate ◼ Binds intracellular cytochrome oxidase = anoxia ◼ Inhalation ◼ Jewelers, labs, smoke inhalation ◼ Local irritant effects ◼ Abdominal pain, nausea, coma, bradycardia, acidosis, CV collapse ◼ Arrest of cellular respiration = aerobic ◼ Bitter almond odor ◼ Treatment metabolism (similar to cyanide) ◼ Amyl nitrite (inhaled) ◼ Sodium nitrite IV ◼ Rotten egg odor ◼ Sodium thiosulfate IV ◼ ◼ Goal is to create a controlled state GI, CNS, CV collapse of methHb to compete for cyanide ◼ Treatment: amyl nitrite, sodium nitrite, ? Hyperbaric oxygen therapy 51 52 Organophosphates ◼ Pesticides/insecticides ◼ Rapidly absorbed ◼ Garlic odor ◼ Muscarinic/cholinergic (SLUDGE): pinpoint pupils, salivation, lacrimation, defecation ◼ Irreversibly binds acetylcholinesterase ◼ Treatment: atropine (high dose- until secretions dry) and 2-PAM (pralidoxime) 53 54 9 1/11/2019 Local Anesthetics ◼ Amides ◼ Lidocaine ◼ Bupivacaine ◼ Much less allergenic ◼ methylparaben ◼ Esters ◼ Tetracaine ◼ Procaine ◼ Side effects: CNS (seizures), CV ◼ Maximum lidocaine dosing ◼ Plain 4mg/kg ◼ with epi 7mg/kg 55 56 GI Symptoms ◼ Onset < 2 hours ◼ Onset 6-24 hours ◼ Chlorophyllum ◼ Gyromitra ◼ Amanita ◼ Amanita ◼ Cantharellus ◼ Activated charcoal ◼ High dose pcn ◼ Treatment ◼ Follow LFT’s ◼ Hydration ◼ Antiemetics 57 58 Muscarinic CNS Excitement ◼ Onset < 30 minutes ◼ Species ◼ Species ◼ Amanita ◼ Inocybe ◼ Symptoms ◼ Clitocybe ◼ Intoxication ◼ Ataxia ◼ Anticholinergic effects ◼ Symptoms ◼ SLUDGE ◼ Treatment ◼ Supportive sedation ◼ Treatment (benzo’s or phenobarb) ◼ Atropine 59 60 10 1/11/2019 Hallucinations Disulfiram ◼ Onset < 30 minutes ◼ Onset 2-72 hours after mushroom ◼ Species ◼ < 30 minutes after ETOH ◼ Psilocybe ◼ Species ◼ Gymnopilus ◼ Coprinus ◼ Treatment ◼ Symptoms ◼ Headache, flushing, ◼ Supportive sedation tachycardia, DIB ◼ Treatment ◼ Supportive 61 62 Highly Poisonous ◼ Castor bean & Jequirity ◼ Poison Hemlock bean ◼ Nicotine effects ◼ Toxalbumin that inhibits ◼ Severe cases: protein synthesis ◼ rhabdomyolysis ◼ Cytotoxic effects on multiple systems ◼ Water Hemlock ◼ GABA antagonist ◼ Oleander & Foxglove & Lily of the Valley ◼ Yew ◼ Digitalis effect ◼ cardiotoxin 63 64 Common Plant Exposures Toxicodendron Species