1/11/2019

Objectives

◼ Drugs of abuse ◼ ◼ Benzodiazepines ◼ Heavy metals ◼ Barbiturates ◼ Cyanide/Hydrogen sulfate ◼ Hallucinogens Review ◼ Organophosphates ◼ Cocaine ◼ ◼ Amphetamines Local anesthetics ◼ Narcotics ◼ Mushrooms David Donaldson, D.O. ◼ Rave drugs ◼ Plants Emergency Medicine ◼ Isoniazid William Beaumont Hospital ◼ Hypoglycemics ◼ Inhalation ◼ Biologic hazards

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Benzodiazepines

◼ Stimulation of the benzodiazepine receptor ◼ Increases the sensitivity of the GABA receptor complex ◼ Leads to inhibitory effects ◼ Lipid soluble

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Clinical Features Treatment

◼ CNS ◼ Activated charcoal ◼ Drowsiness ◼ Elimination enhancement ◼ Dizziness ◼ Not effective ◼ Slurred speech ◼ Respiratory support ◼ Confusion ◼ Ataxia ◼ Paradoxical reactions ◼ Respiratory depression

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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

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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%

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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) ◼ ◼ 6 to 9 times more effective than alkalinization

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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

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Cocaine

◼ Onset ◼ 30 sec to 2 minutes ◼ Peak Effect ◼ 30 minutes ◼ Duration ◼ 1 to 3 hours

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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

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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

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Treatment

◼ Sedation ◼ Benzodiazepines ◼ Fluid resuscitation ◼ Cooling ◼ Whole bowel lavage ◼ Wide complex tachyarrhythmia ◼ Sodium bicarb ◼ Beta-blockers (contraindicated) ◼ Unopposed alpha-adrenergic receptor stimulation

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Amphetamines Treatment

◼ Competitively inhibit the reuptake of ◼ Cardiac monitoring neurotransmitters ◼ Benzodiazepines ◼ Inhibit monoamine oxidase ◼ Avoid beta-blockers ◼ Inhibit the breakdown of catecholamines

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4 1/11/2019

Narcotics

◼ Overdose ◼ Pinpoint pupils ◼ Midrange/dilated if CNS hypoxia ◼ Hypoventilation ◼ Pulmonary edema

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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 ◼ and ◼ Meperidine ◼ Pruritus ◼ Hydromorphone ◼ Oxycodone

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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

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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

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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

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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

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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

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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”

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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

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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

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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 ◼ BAL ◼ Encephalopathy, seizures, parathesias, abdominal pain, EDTA peripheral neuropathy (“classic”=wrist drop) DMSA

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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)

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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)

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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

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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)

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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

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GI Symptoms

◼ Onset < 2 hours ◼ Onset 6-24 hours ◼ Chlorophyllum ◼ Gyromitra ◼ Amanita ◼ Amanita ◼ Cantharellus ◼ Activated charcoal ◼ High dose pcn

◼ Treatment ◼ Follow LFT’s ◼ Hydration ◼

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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

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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

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Highly Poisonous

◼ Castor bean & Jequirity ◼ 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

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Common Plant Exposures Toxicodendron Species

◼ Fava beans ◼ Poison Ivy ◼ G6PD deficiency ◼ Poison Oak ◼ Hemolytic anemia ◼ Sumac ◼ Jimsonweed & Deadly Nightshade ◼ Hallucinatory properties ◼ Anticholinergic crises

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11 1/11/2019

Holiday Plants

◼ Holly ◼ GI symptoms ◼ Poinsettia ◼ Local irritation ◼ Mistletoe ◼ GI symptoms ◼ Easter Lily ◼ Non-toxic

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Isoniazid (INH)

◼ Overdose ◼ Seizure ◼ Coma ◼ Metabolic acidosis ◼ Consider in pediatric seizures ◼ Unintentional OD ◼ Consider in populations likely to be on INH

◼ ◼ Pyridoxine (Vit B-6)

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Oral Hypoglycemic Agents Insulin Toxicity

◼ Prolonged hypoglycemia ◼ Pathognomonic of exogenous insulin ◼ Long half life ◼ Hypoglycemia ◼ Treatment ◼ High insulin levels ◼ Glucose ◼ Suppressed C-peptide levels ◼ Glucagon ◼ Octreotide ◼ Can be severe in children ◼ Treatment ◼ Supportive care (IV glucose) ◼ Admit for observation ◼ Depends on type of insulin

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12 1/11/2019

Nerve Agents

◼ Developed in WWII ◼ Tabun, Sarin, Soman, GF, VX ◼ VX-most potent ◼ Sarin-most volatile ◼ Powerful inhibitors of acetylcholinesterase ◼ SLUDGE ◼ Paralysis ◼ Death

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Nerve Agents

◼ High risk of secondary contamination ◼ Treatment ◼ Oxygen ◼ Atropine ◼ 2-PAM ◼ Military Mark 1 auto injector kit ◼ 2mg atropine ◼ 600g 2-PAM

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Biologic Hazards Anthrax

◼ “wool sorter's disease” ◼ Microorganisms or biological toxins that ◼ Inhalation of spores produce death or disease ◼ Incubation ◼ 1-6 days ◼ Usually stable, highly infectious, with no ◼ Symptoms effective vaccine ◼ Fever ◼ Cough ◼ Undetectable at time of exposure ◼ Chest pain ◼ Fatigue ◼ Most likely route of transmission is respiratory ◼ Sepsis ◼ Death (within 24 hours) ◼ Treatment ◼ Cipro or doxycycline ◼ Vaccine

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13 1/11/2019

Ricin

◼ Cytotoxin ◼ Inhalation ◼ Symptoms ◼ Airway necrosis ◼ Fever ◼ Cough ◼ Sweating ◼ Hemorrhagic pulmonary edema

◼ Treatment ◼ supportive

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Random Pearls Random Pearls

◼ Drug causes of non-cardiogenic pulmonary edema ◼ Over 50% of patients with PCP have nystagmus ◼ Opiates ◼ Phenobarb ◼ Salicylates ◼ Heavy metal poisoning usually presents as a systemic, bizarre complex in which an occupational history is important ◼ Cholinergic poisoning syndrome ◼ Causes: organophosphates and insecticides ◼ X-ray is useful for iron and lead toxicity ◼ SLUDGE ◼ Treatment: Atropine and 2-PAM ◼ Disposition of a hypoglycemia induced by an oral hypoglycemic ◼ The presence of hemorrhagic blisters suggests barbiturate toxicity agent is admission

◼ Opiate overdose ◼ The most common mistake in treating insecticide toxicity is ◼ Respiratory depression, pinpoint pupils, and decreased mental status under-atropinization ◼ Treatment: naloxone

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Random Pearls Random Pearls

◼ Cyanide ◼ Body packer vs. Body stuffer ◼ Binds to cytochrome oxidase resulting in cellular asphyxia ◼ Antidote kit: works by inducing methemoglobinemia ◼ Anticholinergic poisoning associated with Jimson Weed

◼ Pyridoxine is the antidote for INH ◼ Cholinesterase is the enzyme inhibited by organophosphates

◼ The best treatment for cocaine toxicity is ◼ Nitroprusside may induce cyanide toxicity benzodiazepines (Beta-blockers are contraindicated) ◼ Arsine gas presents with the triad: abdominal pain, hematuria, ◼ Charcoal is ineffective for cyanide, iron, lithium, and and jaundice alcohols

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