Toxicology

Drugs of Abuse

Synthetic Cannabinoids (Spice, K2)

  • Symptoms: anxiety, paranoia, tachycardia
  • Unique symptoms compared to traditional cannabinoids: psychosis, seizure, diaphoresis

Hallucinogenic amphetamines (ecstasy, MDMA)

  • Increased serotonergic activity
  • Management: supportive care (IVF, cooling for hyperthermia), benzodiazepines

Gamma-hydroxybutyrate (GHB)

  • Symptoms: euphoria, hypersexuality, rapid onset/clearance
  • Signs: bradycardia, bradypnea, coma with rapid awakening
  • Management: intubation for depressed GCS
  • Withdrawal: symptoms and treatment identical to ethanol withdrawal, consider baclofen

Cathinone (bath salts)

  • Symptoms: hallucinations
  • Signs: tachycardia, hypertension, tremor, mydriasis, diaphoresis, hyperthermia, bruxism
  • Management: benzodiazepines, consider paralysis, avoid beta-blockers

Cocaine

  • MOA: increase catecholamines, Na-channel blockade
  • Toxicity: HTN, tachycardia, hyperthermia, rhabdomyolysis, MI, seizure, VT
  • Management: benzodiazepines, cooling, anti-hypertensives (nitrate, CCB, not B-blocker)

Amphetamine

  • Toxicity: HTN, tachycardia, hyperthermia, rhabdomyolysis, intracranial hemorrhage
  • Management: same as cocaine

Benzodiazepines

  • Toxicity: sedation, respiratory depression
  • Management: consider flumazenil 0.2mg IV q1min x1-5

Toxic Alcohols

  • Overview
    • Toxic metabolites produced by alcohol dehydrogenase which can be inhibited by ethanol or fomepizole
    • Fomepizole: 15mg/kg loading dose, 10mg/kg q12h x4 doses then 15mg/kg q12h (stimulates own metabolism); if dialysis, q4h
  • Diagnosis: osmolar gap (>14), 2Na + Glu/18 + BUN/2.8 + EtOH/4.6
  • Treatment
    • ADH inhibition
    • HCO3
    • Hemodialysis
    • Supportive care
    • Hypoglycemia: dextrose

Methanol

  • Component of antifreeze, windshield washer fluid
  • Metabolite formic acid which causes acidosis and blindness
  • Can give folate

Ethylene glycol

  • Component of antifreeze, automobile coolants, de-icing agents
  • Metabolite oxalic acid which precipitates calcium oxalate crystals and causes acute renal failure
  • Can give thiamine (100mg q6h), pyridoxine (500mg q6h), Mg

Isopropanol

  • Component of rubbing alcohol
  • Metabolite acetone which does not cause acidosis

Analgesics

Acetaminophen

  • Metabolism: glucoronidation, CYP450
    • CYP450 pathway produces toxic metabolite when glucoronidation overwhelmed
    • In pediatrics, sulfation process protective
  • Toxic dose: >150mg/kg, >3g/day
  • Injury: liver (centrilobular necrosis), renal, pancreatic
  • Increased risk: induced CYP450 (chronic EtOH, rifampin, anti-epileptics)
  • Nomogram: applicable to single ingestion at 4-hours
  • Labs: PT/INR, LFT, lipase, chemistry
  • Management: NAC
    • PO: 140mg/kg, 70mg/kg q4h
    • IV: 150mg/kg, 50mg/kg over 4h, 100mg/kg over 16h

NSAID

  • Symptoms
    • Acute: GI upset, low risk UGIB
    • Acute massive: acidosis, coma, seizures
    • Chronic: UGIB, nephropathy, agranulocytosis

Aspirin

  • Signs: tachycardia, hyperthermia, tachypnea/hyperpnea
  • Severe: cerebral and pulmonary edema, CNS hypoglycemia
  • Labs: primary respiratory alkalosis with metabolic acidosis
  • Management
    • Hypoglycemia (CNS) treatment
    • Bicarbonate infusion (urine pH > 8)
    • Hemodialysis for pulmonary edema, cerebral edema, renal failure, acidemia, level >100mg/dL (acute) or > 60mg/dL (chronic)

Opioids

  • Symptoms: respiratory depression, miosis
  • Management: naloxone 0.04mg, 0.4mg, 2mg
  • Withdrawal: nausea/vomiting, diarrhea, abdominal pain, piloerection
    • Neonates: seizure, death
  • Complications with specific agents:
    • Meperidine, tramadol: seizures
    • Methadone: QT prolongation

Anesthetics

Lidocaine

  • Mechanism: Na-channel blockade
  • Types:
    • Ester (one “i”): cocaine, procaine, benzocaine
    • Amide (two “i”): lidocaine, bupivacaine
  • Toxicity
    • Dose: 4mg/kg, 7mg/kg with epinephrine
    • CNS: perioral numbness, slurred speech, seizure
    • CV: VT, VF, AV block
    • Methemoglobinemia: methylene blue
  • Treatment
    • Seizure management
    • Bicarbonate for dysrhythmia
    • Intralipid

Anti-cholinergics

Sympathetic Parasympathetic
Mydriasis Miosis
Bronchodilation Bronchospasm/bronchorrhea
Tachycardia Bradycardia
Urinary retention Urinary incontinence
Hyperglycemia Salivation/lacrimation
Diaphoresis Increased GI motility
  • Examples
    • Atropine
    • Anti-histamine
    • TCA
    • Phenothiazines
    • Jimson weed
  • Symptoms
    • Peripheral: mydriasis, anhidrosis, flushing, hyperthermia, ileus, dry mucous membranes, AUR
    • Central: agitation (passive), delirium, coma, seizure
  • Treatment
    • Supportive
    • Benzodiazepines
    • Theoretically physostigmine
      • Avoid in seizure, QRS-widening, reactive airway disease
      • Possible diagnostic use

Drugs causing miosis (COPS)

  • C: cholinergics
  • O: opioids
  • P: phenothiazines
  • S: sedatives

Drugs causing QT-prolongation

  • Examples:
    • Phenothiazines
    • Anti-arrhythmics
    • Butyrophenones (ex. haloperidol)
    • Macrolides
    • Fluoroquinolones
    • Methadone
    • Ondansetron
    • Atypical antipsychotics
  • Treatment
    • Magnesium sulfate 2g IV over 1min
    • Overdrive pacing (transcutaneous, transvenous if not captured)
    • Consider isoproterenol (pharmacologic overdrive)

Serotonin syndrome

  • Cause: exposure to serotonergic agent(s)
  • Symptoms: agitation, mydriasis, tremor/clonus in lower extremities, tachycardia, hyperthermia
  • Management
    • Supportive care (IVF, vasopressors)
    • Cooling measures and paralysis for hyperthermia
    • Benzodiazepines
    • Cyproheptadine 12mg PO/NG
    • Dexmedetomidine infusion

Anti-emetics

Phenothiazines

  • Examples: compazine (prochlorperazine), phenergan (promethazine)
  • MOA: DA-antagonist
  • AE: sedation, dystonia, parkinsonism
  • Toxicity: seizure, VT, hypotension (TCA-like)

5-HT3 antagonists

  • Examples: zofran (ondansetron), granisetron
  • Toxicity: QT-prolongation

Anti-hypertensives

Calcium channel blockers

  • Toxicity: hypotension, bradycardia, AV blockade, hyperglycemia
  • Management
    • Atropine: 0.5mg IV q2-3min
    • Glucagon: 5mg IV q10min x2 (with anti-emetic)
    • IVF, vasopressors (norepinephrine, epinephrine)
    • Calcium: 3g gluconate, 1-3g chloride
    • High-dose insulin: 1 unit/kg, monitor hypoglycemia/hypokalemia
    • Intralipid: 1.5mL/kg bolus then 0.25mL/kg/minute
    • GI decontamination
    • Pacing, IABP, ECMO

Beta blockers

  • Toxicity: similar to CCB, hypoglycemia
  • Management: similar to CCB, calcium ineffective

Digoxin (foxglove, oleander)

  • MOA: inhibits Na/K ATPase, increases intracellular calcium (inotropic)
  • Toxicity
    • CV: bradycardia, hypotension
    • ECG: bidirectional VT, PVC, scooped ST-segment
    • CNS: agitation, psychosis
    • Visual: yellow-green vision, halo
    • Metabolic: hyperkalemia (acute), hypokalemia, hypomagnesemia
  • Treatment
    • GI decontamination
    • Atropine
    • Transcutaneous pacing (avoid transvenous, irritable myocardium)
    • Digibind
    • Avoid calcium

Clonidine

  • Toxicity: bradycardia, hypotension, opioid mimic (miosis, lethargy, respiratory depression)
  • Management: supportive care, stimulation for respiratory depression, atropine

Sodium-channel blockers

  • Drugs
    • TCA
    • Diphenhydramine
    • Procainamide
    • Carbamazepine
  • ECG
    • QRS prolongation
    • Prominent “R” in aVR
    • RAD
  • Treatment
    • Sodium bicarbonate

Anti-hyperglycemics

Sulfonylurea

  • Symptoms: recurrent severe hypoglycemia
  • Management: octreotide 50-75mcg SQ/IM q6h

Other agents that cause hypoglycemia

  • EtOH
  • B-blocker
  • Quinine
  • Salicylate

Environmental

Carbon monoxide

  • Source: combustion (gas heater, indoor barbeque)
  • Toxicity
    • General: influenza-like, multiple proximate affected individuals
    • GI: abdominal pain, nausea
    • CNS: headache, dizziness, confusion, ataxia, seizure
    • CV: palpitations, arrhythmia, hypotension, MI
  • Treatment
    • T½: RA 6h, NRB 1h, 3atm 0.5h
    • Hyperbaric: neuro deficit, syncope, pregnancy, CV toxicity

Cyanide

  • Mechanism: inhibits oxidative phosphorylation
  • Source: structural fire (wool, silk)
  • Symptoms: syncope, seizure, coma, cardiovascular collapse
  • Detection: severe lactic acidosis, “arterialization” of venous blood, “bitter almond” odor
  • Treatment
    • Hydroxycobalamin (Cyanokit): 5g IV, may repeat x1
    • Sodium thiosulfate 12.5g IV

Methemoglobinemia

  • Mechanism: Fe2+ converted to Fe3+, “functional anemia”
  • Source: nitrite (food), topical/local anesthetics, pyridium, dapsone, reglan
  • Detection: normal PaO2, SpO2 85% unresponsive to supplemental oxygen, ABG with co-oximetry
  • Management: methylene blue 1-2mg/kg IV if symptomatic or MetHb >25%
    • Contraindicated in G6PD deficiency, treat with exchange transfusion or HBO

Hydrogen Sulfide

  • Source: industrial, sulfur spring, sewer
  • Detection: “rotten egg” odor
  • Management: remove from source, supportive care

Hydrocarbon

  • Source: huffing canisters
  • Toxicity: VT/VF from myocardial sensitization
  • Management: beta-blockade
  • Complications: harmless if ingested, aspiration leads to ARDS

Hydrofluoric acid

  • Source: rust remover, wheel cleaner, glass etching
  • Symptoms: pain-out-of-proportion, delayed onset
  • Toxicity: Hypocalcemia (QTc prolongation, VT/VF/TdP), hyperkalemia, hypomagnesemia
  • Management: analgesia, topical calcium gluconate gel, intravenous calcium for large BSA involvement

Alkaline ingestion

  • Symptoms: esophageal perforation, delayed stricture

Acid ingestion

  • Symptoms: gastric perforation (rare), delayed gastric outlet obstruction
  • Findings: metabolic acidosis

Botulism

  • Sources
    • Adult: ingested preformed toxin
    • Infants: ingested spores (achlorhydric), in vivo toxin production
    • Wound: black tar heroin
  • Symptoms: dysphagia, ptosis, diplopia, respiratory failure, descending paralysis
    • Infants: constipation, floppy
  • Management: supportive care, intubation
    • Adults: Anti-toxin from CDC or local Department of Health
    • Infants: 100mg/kg IV x 1 dose (BabyBIG)

Heavy Metals

Iron

  • Dose
    • Ferrous sulfate: 20% elemental iron
    • Toxic: >20mg/kg
    • Lethal: >60mg/kg (1 tablet 325mg ferrous sulfate per kilogram)
  • Toxicity: corrosive, anti-coagulant, hepatotoxic
  • Course
    • Stage I: GI effects, emesis with hematemesis
    • Stage II: Quiescent
    • Stage III: Systemic, multi-organ system dysfunction
    • Stage IV: Resolution, gastric scarring and outlet obstruction
  • Workup
    • CBC/BMP
    • LFT
    • Lactate
    • Fe level
    • KUB (if positive consider WBI)
  • Treatment
    • Decontamination: no activated charcoal, consider WBI
    • Deferoxamine: 15mg/kg/hr

Lead

  • Source: paint, batteries
  • Toxicity
    • Acute: headache, encephalopathy, seizure
    • Chronic: malaise, weight loss, arthralgia, anemia (basophilic stippling)
  • Diagnosis: lead level, wrist drop
  • Management: chelation (BAL, EDTA, DMSA) for level >50ug/dL or asymptomatic >70ug/dL

Lithium

  • Source: iatrogenic, drug-drug interaction
  • Symptoms
    • GI: nausea/vomiting, diarrhea
    • CNS: tremor, coma
    • CV: TWI, QT-prolongation
  • Management
    • IVF, encourage renal elimination
    • Hemodialysis

Other Drugs

Disulfuram

  • MOA: aldehyde dehydrogenase inhibitor
  • Symptoms: increased acetaldehyde leads to flushing, headache, nausea/vomiting, tachycardia, hypotension
  • Management: antihistamine, IVF, vasopressors
  • Other agents causing disulfuram-like reaction: metronidazole, INH, sulfonylurea

Isoniazid

  • Toxicity: seizure
  • Management: pyridoxine 5g IV, repeat x1

Theophyline

  • Toxicity: seizure
  • Management
    • Decontamination: AC
    • Seizures: benzodiazepines
    • Tachyarrhythmia (commonly MAT): beta-blockade
    • Hemodialysis: acute > 100mg/L, chronic >30mg/L

Monoamine oxidase inhibitors

  • Toxicity: food/drug interaction
  • Symptoms: tachycardia, hypertension, hyperthermia, agitation
  • Management: cooling, IVF, management of hyper/hypotension

Phenytoin

  • Oral: cerebellar dysfunction (ataxia), CNS depression
  • IV: hypotension (suspension contains propylene glycol)

Nutritional Supplements

  • Fat-soluble vitamins
    • A: benign intracranial hypertension
    • D: hypercalcemia

Envenomations

Snake

  • Crotalid (rattle), elapidae (coral)
  • Symptoms
    • Local reaction: edema, hemorrhagic bullae
    • Systemic: perioral numbness, fasciculations
    • Severe: thrombocytopenia, decreased fibrinogen
  • Management: Crofab 5 vials

Spider

  • Black widow
    • Identification: hourglass on abdomen
    • Symptoms: painful bite, target-appearance, rarely “acute abdomen”
    • Management: analgesia, anti-venom, tetanus
  • Brown recluse
    • Identification: violin shape on head
    • Geography: Southeast, Midwest
    • Symptoms: painless bite, local reaction, delayed healing with eschar
    • Rare: hemolysis, DIC, shock
    • Management: supportive care, antibiotics if superinfected, consider dapsone, tetanus

Scorpion (Centruroides)

  • Geography: Arizona
  • Symptoms
    • Autonomic: HTN, tachycardia, diaphoresis
    • CNS: opsoclonus, slurred speech, dysphagia
  • Management: anti-venom, supportive care, analgesia, tetanus

Marine

  • Ciguatera
    • Source: toxin bioconcentrated in fish
    • Symptoms: gastroenteritis, hot/cold-reversal, “loose teeth” sensation
    • Management: mannitol
  • Scombroid
    • Source: poorly-refrigerated fish, histamine-like
    • Symptoms: flushing trunk/face (distinguish from allergic reaction), gastroenteritis
    • Management: supportive care, IVF, anti-histamine, bronchodilators if indicated
  • Paralytic shellfish poisoning
    • Source: bivalve
    • Symptoms: gastroenteritis, paralysis
    • Management: supportive, intubation
  • Jellyfish and Cnidaria
    • Source: nematocyst
    • Symptoms: burning pain, pruritus
    • Severe: Irakundji syndrome (HTN, pulmonary edema)
    • Management: supportive, analgesia, box jellyfish antidote, consider vinegar
  • Stingray
    • Source: heat-labile toxin
    • Management: affected area in warm water, tetanus, ciprofloxacin (Vibrio)

Mushrooms

  • Amanita: centrilobular necrosis, similar to acetaminophen
  • Gyronatum: similar to INH (seizure and treatment), may cause methemoglobinemia
  • Symptoms: muscarinic (SLUDGE)
    • Early onset generally benign, delayed onset (>6h) suggests more serious course
  • Management: atropine, glycopyrrolate, IVF

Pesticides

  • Organophosphate: irreversible
  • Carbamate: reversible
  • Symptoms: muscarinic (SLUDGE)
  • Treatment: atropine 2-6mg IV double q5min to control secretions, pralidoxime (for organophosphates)

Strychnine

  • Source: rodenticide
  • Symptoms: myoclonus, opisthotonus, agitation
  • Management: benzodiazepines, airway protection, paralysis

Atypical Antipsychotic Overdose

History & Physical

38M, unknown medical history, brought in after being found unresponsive next to an empty bottle of Seroquel. Presenting vital signs notable for blood pressure of 96/43, heart rate 103. Examination reveals tentatively protected airway (GCS E2 M5 V3, SpO2 100%, RR 14), normal pupil diameter and reactivity, dry mucous membranes with thick vomitus in oral cavity.

Laboratory evaluation was unremarkable, and there was no evidence of aspiration on chest radiography. ECG showed sinus tachycardia without QT prolongation. Blood pressure increased to normal range with fluid resuscitation. The patient’s mental status progressively improved and he was discharged after six hours of uneventful continuous cardiac monitoring.

Toxidrome Summary1

Class Vital Signs Mental Status Pupils Skin Other Examples
Anti-cholinergic T
HR
BP
Delirium
Agitation
Coma
Mydriasis Dry Urinary retention
BS
Anti-histamines
Anti-parkinson
Anti-psychotic
Anti-depressant
Sympathomimetic T
HR
BP
Agitation
Hallucination
Paranoia
Mydriasis Diaphoresis Tremor
Hyperreflexia
Cocaine
Amphetamine
Ephedrine
Opioid/Sedative HR
RR
BP
CNS depression
Coma
Miosis   Hyporeflexia
Needle marks
Opioids
Benzo
Barbiturates

Evaluation1,2

  • POC Glucose
  • ECG (QT interval)
  • Serum acetaminophen, salicylate, EtOH level
  • Serum drug levels if known (anti-epileptics)
  • Urine toxicology screen
  • Chemistry (metabolic acidosis, electrolytes, renal function)
  • LFT (hepatotoxicity)
  • CK (rhabdomyolysis)
  • Serum osmolarity (osmolar gap)
  • UA with microscopy (crystals in ethylene glycol poisoning)
  • ABG (carboxyhemoglobin, methemoglobin)

Pharmacology, Toxicity and Management of Second Generation Antipsychotic (SGA) Overdose3

Pharmacology, Toxicity and Management of Second Generation Antipsychotic (SGA) Overdose

References

  1. Kulig, K. (2013). General Approach to the Poisoned Patient. In Rosen’s Emergency Medicine – Concepts and Clinical Practice (8th ed., Vol. 1, pp. 1954-1959). Elsevier Health Sciences.
  2. Wittler, M., & Lavonas, E. (2013). Antipsychotics. In Rosen’s Emergency Medicine – Concepts and Clinical Practice (8th ed., Vol. 1, pp. 2047-2051). Elsevier Health Sciences.
  3. Levine M, Ruha A-M. Overdose of atypical antipsychotics: clinical presentation, mechanisms of toxicity and management. CNS Drugs. 2012;26(7):601–611.
  4. WikEM: Antipsychotic toxicity

“Gastosin” Ingestion

Jalapa, NicaraguaCC:

“Gastosin” ingestion

HPI:

29F BIB family after patient was found down at home, near opened bottle of Gastosin in presumed suicide attempt. On arrival to ED, patient was awake, but unresponsive, groaning and clutching stomach. GCS  was E3-V2-M5, HR 110, BP 60/palp, RR 24.

ED Course:

Upon arrival, placed two large-bore IV w/rapid infusion of 2L NS and given DA 2g IV x2. NG tube placed, initiated lavage of gastric contents with NS. Patient’s mental status continued to deteriorate, became unresponsive.

PMH/PSH:

Unknown

SHx:

History of alcohol abuse and depression per family.

PE:

  • VS: 110bpm, 60/palp, 24 R/min, no temp/O2sat available
  • General: Ill-appearing female, laying on bed in considerable distress, groaning and clutching stomach, diaphoretic
  • HEENT: NC/AT, PERRL (4-3mm), EOMI, MMM no lesions, no tongue lacerations, breath with foul odor, TM’s clear b/l.
  • CV: RRR, normal S1/S2, tachycardia, faint heart sounds, JVP elevated though patient supine
  • Lungs: CTAB, no crackles/wheezes
  • Abdomen: +BS, soft, non-distended, no guarding, no ecchymosis
  • GU: Normal external genitalia, loss of stool noted.
  • Neuro: Patient confused, initially responsive to sternal rub, moving all 4 extremities spontaneously/equally, EOMI without nystagmus, gag reflex present, DTR 2+ and symmetric throughout with toes downgoing.
  • Extremities: Cool, peripheral pulses 0 (radial, PT, DP), 1+ (femoral, brachial, carotid)1, capillary refill 3sec
  • Skin: No visible skin lesions

Assessment & Plan:

29F, unknown PMH, ċ ingestion of unknown amount of “Gastosin”. Patient presenting in likely cardiogenic shock given hypotension with reflex sympathetic activation (evidenced by peripheral vasoconstriction à cool extremities, diaphoresis) and no evidence of hemorrhage. Gastosin is a pesticide used in the storage of maize2, and is well-known locally as a common agent in self-poisonings. Chemically composed of aluminum phosphide, and liberates phosphine gas on exposure to moisture which is rapidly absorbed by inhalation, transdermally or gastrointestinally. Toxicity results from free radical damage and inhibition of enzymes of metabolism (particularly affecting cardiac myocytes). Clinical features include vomiting, resistant hypotension and metabolic acidosis.3

Patient’s symptoms and presentation are consistent with cardiogenic shock secondary to Gastosin ingestion. Management included fluid resuscitation and inotropic support with dopamine, as well as gastric lavage. Resuscitation efforts were unsuccessful and patient remained hypotensive with worsening of mental status, and eventual death.

Differential Diagnosis for Shock:

A System for Shock

A System for the Management of Aluminum Phosphide Poisoning:4,5

Management of Aluminum Phosphide Poisoning

The Glasgow Coma Scale:

  Eye Opening Best Motor Response Best Verbal Response
1 None None None
2 Pain Extension Groans
3 Verbal Flexion Unintelligible
4 Open Withdraws Disoriented
5 Localizes Oriented
6 Obeys commands

References:

  1. Hill RD, Smith RB III. Examination of the Extremities: Pulses, Bruits, and Phlebitis. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 30. Available from: http://www.ncbi.nlm.nih.gov/books/NBK350/
  2. Udoh, J., Ikotun, T., & Cardwell, K. (n.d.). Storage systems for maize (zea mays l.) in nigeria from five agro-ecological zones. Proceedings of the 6th International Working Conference on Stored-product Protection, 2, 960-965.
  3. Bogle, R. G., Theron, P., Brooks, P., Dargan, P. I., & Redhead, J. (2006). Aluminium phosphide poisoning. Emergency medicine journal : EMJ, 23(1), e3. doi:10.1136/emj.2004.015941
  4. Gurjar, M., Baronia, A. K., Azim, A., & Sharma, K. (2011). Managing aluminum phosphide poisonings. Journal of Emergencies, Trauma, and Shock, 4(3), 378–384. doi:10.4103/0974-2700.83868
  5. Jones, A. L., & Volans, G. (1999). Management of self poisoning. BMJ (Clinical research ed.), 319(7222), 1414–1417.