Transcript Document

Amy Gutman MD
[email protected]
EMS Medical Director
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Impossible to cover all
tox emergencies in 90
minutes!
Review pharmacology,
assessment &
management
“Major players” of illicit &
prescribed medications
commonly causing toxicity
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Social History
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• Group vs individual
• Drugs, Alcohol, Smoking
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Allergies
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Medications
• Prescribed & Illicit
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PMH
• ODs, SI, HI, medical Hx
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Last Oral Intake
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Events
• WWWWW H
Who:
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What:
• What & how much?
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Where:
• Is the scene safe?
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Why:
• SI vs accidental
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How:
• Route of exposure
• Ingestion, Inhalation,
Absorbtion
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Vitals are Vital
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Physical exam clues help with identifying toxin
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In most cases, it’s not immediately important what toxin is,
rather treating effects of the exposure
Always “assume” patient is lying
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Focus on supportive therapy rather than toxin identification as
it is often complicated by a poor or “creative” historian
1. IV / O2 / Monitor
2. Airway management
3. Altered mental status (AMS) protocol including glucose check
4. Symptomatic management of nausea, vomiting, seizures
5. Early & effective decontamination

For all toxins above steps are part of the general management
 Miosis
• Sympathomimetics
• Cholinergics
• Clonidine
• Nicotine
• PCP
 Mydriasis
• Anticholinergics
• Opiates
• Sympathomimetics
 Decreased
 Increased
• Alcohols
• CO
• Barbituates
• Cyanide
• Benzodiazepines
• Salicylates
• Opiods
 Tachycardia
• Anticholinergics
 Bradycardia
• Alpha, Beta & Calcium
• Antihistamines
• Antidepressants
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• PCP
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• Sympathomimetics
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Channel Blockers
Digoxin
Cholinergics
Cyanide
Nicotine
 Hypertension
• Anticholinergics
• Antihistamines
• Antidepressants
• PCP
• Sympathomimetics
 Hypotension
• CO
• Cyanide / Iron
• Antidepressants
• Opioids
• Sedative-Hypnotics
 Hyperthermia
 Hypothermia
• Anticholinergics
• Beta Blockers
• MAOIs
• CO
• PCP
• Cholinergics
• Salicylates
• Ethanol
• Sympathomimetics
• Hypoglycemics
• Sedative-Hypnotics
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Alcohols
Anticholinergics
Cholinergics
Heavy Metals
Beta Blockers
CO
Antidepressants
Lithium
Opiods
PCP
Antipsychotic
Salicylates
Sedative-Hypnotics
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Based upon neurotransmitter
stimulated or receptor triggered
by a chemical reaction
Symptoms result from having
“too much” or “too little” of a
neurotransmitter or chemical
Most symptoms secondary to
nervous system effects
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Acetylcholine
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Dopamine
Serotonin
Norepinephrine
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Primary neurotransmitter in brain “reward pathways”
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“Dopaminergic” drugs produce euphoria
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Over time neurons require more & more dopamine
stimulation to produce euphoria, or “tolerance”
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Dopamine stimulant fools neurons into releasing dopamine to
send a “pleasure” message
• Also stimulates serotonin & norepinephrine
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Highly addictive, causing intense pleasurable rush followed by
a euphoric high lasting for 12+ hours
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User experiences severe depression as euphoria dissipates
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Powder or clear chunky crystal from an odorless, bitter-tasting,
crystalline powder that is ingested, snorted, injected or inhaled
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#2 illicit drug worldwide, #1
illicit drug in US
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20%-30% labs discovered
after a fire or explosion
• Police & EMS most often
injured during explosions
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Previously prescribed to
treat obesity, sexual
dysfunction, narcolepsy &
ADHD
Asian factories supply
workers with meth to
maintain productivity in
tedious & repetitive tasks
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12.3 million (5% Americans)
have tried meth
• 1.5 million daily users
• 10% high school have tried meth
• In CA, 60% of those arrested test
positive for meth
• 50x more likely to abuse other
drugs
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Use associated with:
• Men having sex with other men
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& use drugs
Young adults attending “raves"
Homeless youth
Sex workers
Occupations demanding long
hours, mental alertness &
physical endurance
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Euphoria, alertness or wakefulness
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Feelings of increased strength, energy,
confidence & sexual desire
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Hallucinations / Formication
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Physiological changes:
• Tachycardia, arrhythmia, HTN, SOB,
hyperthermia, seizures, MI
• Anxious, irritable, paranoid
• Unpredictable & dangerous behavior when
startled or confronted
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Post High:
• Irritability, insomnia, confusion, extreme
paranoia, amnesia, fatigue, hallucinations,
severe depression
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Haz Mat situation with exposure to
volatiles, spills, fires & explosions
• Household & agricultural chemicals, gas, ephedrine, pseudoephedrine
• Inhalation, ingestion & skin absorption leading to respiratory & eye
irritation, HA, dizziness, N/V/D & SOB
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1 lb of meth produces 5 lbs of toxic, flammable waste
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Scene safety #1, then identify immediate threats to life
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If suspected user reports chest pain &/or has symptoms of an MI,
treat as per standard protocols
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Treat any medical or traumatic illness as per your local protocols
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Children at >25% of labs
• Sustain physical, developmental & psychological hazards
• 3x greater likelihood of physical & / or sexual abuse
• Likely to imitate parents' behaviors
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Hazard Exposure:
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Weapons / Explosives
Rodent & insect infestation
Rotten food & garbage
Inoperative heater, air conditioner, toilets & running water
Drug paraphernalia
Dangerous animals
You are a mandatory reporter, required to file a 51A
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ACh is an excitability, arousal & reward
neurotransmitter with effects on learning & memory
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Cholinergics produce mimic, or release acetylcholine
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Think “Organophosphate Insecticides”
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Bethanacol
Edrophonium
Physostigmine
Pilocarpine
Nicotine
Toxicologic hallmark is DUMBELS / SLUDGE
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Defecation / Diarrhea
Urination
Miosis
Bronchorrhea/ Bradycardia
Emesis / GI Distress
Lacrimation
Salivation
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Prehospital Management:
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Airway Management
Seizure Management
Gastric decontamination
Atropine & Pralidoxime (2-PAM) - Mark I Kit
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Substances that block or decrease ACh
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Antihistamines
Antipsychotics / Antidepressants
Belladonna / Mushrooms
Muscle Relaxants & Antispasmodics
Mydriatics
Atropine
Classified according to receptors affected:
• Antimuscarinics & Antinicotinics
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Considered least "fun" recreational drug
• Lack of euphoria
• Low risk of dependence
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“Hot as a Hare”
• Fever
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“Dry as a Bone”
• Dry Skin / Xerostomia / Ileus / Urinary Retention
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“Red as a Beet”
• Flushed skin
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“Mad as a Hatter”
• Psychosis / Hallucinations / Delirium / Agitation / Amnesia
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Other
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Tachycardia
Increased Intraocular Pressure / Mydriasis / Diplopia
Ataxia / Choreoathetosis / Seizures / Coma
Respiratory depression
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Chief inhibitory neurotransmitter
Disrupted GABA signal causes
neuro & psychiatric pathologies
including movement & anxiety
disorders, epilepsy, schizophrenia
& addiction
Drugs affecting GABA receptors:
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Alcohol
Barbiturates
Benzodiazepines
Baclofen
Anti-epileptics
Gamma-Hydroxybutyric acid (GHB)
Propofol
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GABA stimulating
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Widespread legal & illicit use
• Anxiety, depression, pain
• Date rape drug
• Toxicity worsened if used with
alcohol or other sedatives
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SSX:
• AMS, amnesia, hallucinations
• Dizziness, ataxia, weakness,
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slurred speech
Drowsiness, paradoxical
agitation
Blurred vision, nystagmus
Respiratory depression
Hypotension
Coma / Death
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Management
• Charcoal w/ little prehospital
utility & contraindicated if
somnolent
• AMS Protocol & aggressive
airway support
• Hypotension rare
 Search for another cause
• Never use benzodiazepine
antagonist flumazenil
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GABAenergic drugs
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“Anesthesia plus Amnesia”
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Drugs:
• Ketamine, Rohypnol, GHB
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SSX:
• Sedation, slurred speech,
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coma
Confusion, delirium,
hallucinations
Paresthesias, dysesthesias
Diplopia, blurred vision,
nystagmus
Ataxia
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Disassociative amnestic / anesthetic
structurally resembling PCP
• CNS depressant, rapid-acting
general anesthetic, sedativehypnotic, analgesic & hallucinogenic
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Symptoms
• Impaired motor function
• Pulmonary edema
• Delirium, hallucinations, out of body
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experiences, vivid Dreams
Seizures, dystonia
Vomiting
Arrhythmias, cardiac arrest
Coma
Treatment:
• Benadryl for dystonia
• Benzodiazepines for sedation
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Anticholinergic
• Dry skin, miosis
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Dopaminergic / Norepinephrine
• Agitation, delusions
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Opiate
• Altered pain perception
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Serotonin
• Altered perceptions
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GABA Inhibition:
• Excitation
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Same treatment guidelines as
ketamine
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GABAenergic anesthetic / sedative often used as a bodybuilding aid
Clear liquid, white powder, tablet or capsule often carried in a
water bottle or eye dropper
Used in combination with alcohol to increase effect
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“Amnesia +
suggestiveness”
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• Sudden airway collapse &
aspiration
• Avoid respiratory
depressants
• Hypothermia, lethargy,
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somnolence
Dizziness, AMS
Euphoria
Vomiting
Bradycardia
Respiratory depression,
coma
Seizures, myoclonic
jerking
Avoid positional asphyxia
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Unpredictable clinical
course with rapid changes
in mental & respiratory
status
Presentation & treatment
mimic ETOH intoxication
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Benzodiazepine, sedative-hypnotic,
respiratory depressant, amnestic
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Date rape drug often placed in
alcoholic drinks for ingestion
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Odorless, tasteless, dissolves easily
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Clonazepam often used as a roofie
“alternative”
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SSX:
• Sedation, amnesia, suggestiveness
Treatment:
• Supportive
• Often will not seek care until
effects of drug wear off
• Suspected ingestions treated as
criminal cases
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Stress hormone & catecholamine synthesized from dopamine
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Fight-or-flight response increases HR, triggering release of
glucose & increasing blood flow to muscle
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Increasing BP triggers compensatory baroreceptor reflex
resulting in paradoxical bradycardia
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Typical Sympathomimetics
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Cocaine
MDMA (Ecstasy)
Phencyclidine (PCP)
Amphetamine / Methamphetamine
Ephedrine / 2-agonists
Caffeine
Nicotine
Dextromethorphan (DMX)
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Tachycardia, arrhythmias
HTN, aortic dissection, ICH
Hyperthermia
Agitation, delirium, seizures
Myocardial infarction, angina
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Sympathomimetic Toxidrome
“HITTER”
Hallucinations
Insomnia
Tremor
Tachycardia
Excessive Speech & Motor
Activity
• Restlessness
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Arrhythmia management
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Reduce temperature
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Restrain to prevent harm
• Chemical > physical restraints
• Benzodiazepines, haloperidol
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Avoid beta blockers
• Leaves unopposed adrenergic stimulation
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Tachycardia / Arrhythmias
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HTN
• Occasionally hypotensive with
reflexive bradycardia
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CNS stimulation
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Treatment:
• Sedation
• Treat hyperthermia
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“Feel Good Drug” suppresses need to eat, sleep or drink
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Similarities to hallucinogens & amphetamines
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Ingested, inhaled, injected
• Often mixed with PCP
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Blocks reuptake & release of serotonin & dopamine
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Effects within 15 mins include euphoric & energy “rush”
followed by a 2-3 hour plateau then fatigue
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Malignant Hyperthermia
DIC
AMS, stroke
Seizures, tremors
Tachycardia, HTN, CHF
Jaw Clenching, bruxism
Nystagmus, mydriasis
Hallucinations, panic attacks
Syncope, vertigo
Dehydration
Secondary Hyponatremia
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Treatment
• Calm environment
• Active cooling if indicated
• Chemical / physical restraints
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Mu-opiod receptor stimulation
• Narcotics
• Some sedative anesthetics
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SSX:
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Pinpoint pupils
Respiratory depression
Bradycardia hypotension
Hypothermia
Pulmonary edema
Seizures
,
Treatment
• Naloxone / Narcan
• Airway management
• Symptomatic
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Cough suppression via opiate agonist
activity
• Effects related to ketamine, PCP, opiates
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OTC Robitussin Maximum Strength (not DM)
cough syrup
Disassociative anesthetic with a 2-4 hr
duration
Effects at low dosage similar to alcohol
• Carefree clumsiness / vertigo
• Vivid hallucinations (auditory, visual,
tactile)
• AMS, violent outbursts, seizures, coma
• Hyperthermia, HTN, tachycardia
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Long Term ~ Olney's Lesions
• Brain vacuoles cause impaired memory
& schizophrenia-like syndrome
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Coricidin Cough & Cold Caps:
• 30 mg DXM + 4 mgs of
Chlorphineramine maleate
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Respiratory depression occurs at
twice recommended dose
Treatment for suspected ingestion
• Benadryl for dystonic reactions
• Be wary of acute agitation, violent
outbursts & psychotic outbursts
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Even a single tablet of a beta
blocker, calcium channel
blocker, hypoglycemic agent or
mood stabilizer can be fatal to a
child
Although most of these
medications are “dose
dependant”, they can have fatal
effects with a single dose
Many ODs are “AMS +”… deadly
“prescribed” polypharmacy
Don’t forget OTCs & herbs….
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Prescribed for
• HTN, Angina, Hyperthyroid, Migraine,
Glaucoma, SVT
MOI
• 1 Cardiac & 2 peripheral influence
• Selective & non-selective agents
Toxic Dose is 2-3 x therapeutic dose
• May still have “symptoms” at nontoxic dosages
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Bradyarrhythmia
Hypotension
AMS
Respiratory depression
Seizure (pediatrics > adults)
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Prehospital Management
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Atropine
Glucagon
Transcutaneous Pacemaker
Fluid resuscitation & vasopressors
 Dopamine
 Epinephrine
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Treatment for:
• Angina, HTN, Migraine, SVT, ICH
• Nicardipine for intracranial processes
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Blocks calcium entrance into cardiac & smooth muscle cells
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Negative inotrope, chronotrope, dromotrope
• Decreased automaticity at SA & AV nodes
• Decreased PVR
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Hypotension
Bradycardia
Arrythmias
Respiratory depression
Seizures
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Prehospital
Management
• Atropine
• Glucagon
• Transcutaneous
Pacemaker
• Fluid resuscitation &
vasopressors
 Dopamine
 Epinephrine
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Prescribed for HTN, withdrawal, migraine, ADHD, Tourette’s
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 adrenergic agonist
• Toxic effects mimic barbiturate / opiate OD
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Cardiovascular: bradycardia, arrhythmias, hypotension w/ refractory
hypertension post abrupt withdrawal
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Neurological effects: miosis, respiratory depression, seizures, coma
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Treatment
• Atropine
• Narcan
• Glucose
• Transcutaneous Pacemaker
• Fluid resuscitation & vasopressors
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Cardiac glycoside
• Looks like “regular” atrial
fibtillation
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Prescribed for:
• CHF (Improves cardiac
output), A-fib
(antiarrythmic)
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Mechanism of Action
• Increased intracellular
calcium & increases
myocardial contractility
• Narrow therapeutic window
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SSX:
• Nausea/vomiting
• Mental status changes
• Cardiovascular symptoms
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Arrhythmias ~ Any!
• PVC / PAC, AF, PAT w/block,
bradycardia, VF, VT
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Hypotension
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Hyperkalemia
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CNS
• Delirium, lethargy, agitation,
ocular disturbances (blue-green
halos)
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Gastric decontamination
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Never give calcium due to
underlying hyperkalemia
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Atropine & transcutaneous
Pacemaker
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Arrhythmia management
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Digibind:
• Life-threatening CV toxicity
• K+ >5.5 mEq/L
• Level >10 ng/mL or ingested >10 mg
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1 million ODs annually,
400 fatalities
Increases norepinephrine
& serotonin, histamine &
acetylcholine
Most Common
Prescribed
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Amitriptyline (Elavil)
Clomipramine (Anafranil)
Desipramine (Norpramin)
Doxepin (Sinequan)
Imipramine (Tofranil)
Nortryptyline (Pamelor)
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Onset 90 mins – 4 hours post ingestion
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Anticholinergic
– Hyperthermia, blurred vision, flushed skin, hallucinations,
tachycardia, seizures
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Quinidine-like
– Negative inotrope, long QT, ventricular arrhythmias (torsades)
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-Adrenergic blockade
– Hypotension
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CNS
– Drowsiness, AMS, hallucinations, coma, seizures, mydriasis
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Torsades
• Magnesium, overdrive pacing
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Arrythmias
• Standard protocols & meds
• Sodium bicarbonate, lidocaine,
bretylium
• Procainamide & amiodarone
contraindicated
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Seizures
• Benzodiazepines
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Hypotension
• Fluid resuscitation & vasopressors
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Modulates anger, temp,
aggression, mood, sleep,
sexuality, appetite,
metabolism & stimulates
vomiting
Drugs targeting serotonin
used to treat psychiatric
disorders
Confusing name ~
Selective Serotonin Reuptake
Inhibitors increase serotonin
(“serotonergic”)
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Most common prescribed
anti-depressants
Decrease serotonin (5HT)
reuptake to increase
serotonin levels
SSX of OD:
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N/V
Lethargy / Sedation
Arrythmias
AMS / Decreased LOC
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Ingestions of multiple serotonergic agents
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Mortality 10-20% from CV & neurovascular collapse
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Triad of AMS, autonomic hyperactivity &
neuromuscular abnormalities w/i 2 hrs of ingestion
• Neurobehavioral:
 AMS, agitation, seizures, hyperactivity
• Autonomic:
 Hyperthermia, diaphoresis, diarrhea, tachycardia, HTN,
salivation
• Neuromuscular:
 Myoclonus, hyperreflexia, tremor, muscle rigidity
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18 yo student admitted to the
hospital with fever of 103.5,
agitation, AMS, “jerking
motions”
Taking phenelzine (MAOI
antidepressant), heroin & THC
Given meperidine / demerol in
the hospital for agitation, which
increased agitation eventually
leading to physical restraints
6 hrs later at a temp of 107 she
arrested & died
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Ms. Zion seen only by an intern & 2nd
year resident with responsibility for 40
pts in their 36 hour shift
Instead of recognizing SSX of
serotonin syndrome, treated pt for
“drug-related agitation & psychosis”
Zion’s father (a reporter for the NY
Times) reported his daughter’s death
in the NY Times, Newsweek,
Washington Post & 60 Minutes
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In 1989 NY adopted an 80 hr resident
work week w/ supervision guidelines
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All residencies adopt guidelines by
2004
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Respiratory support
Fever control
Sedatives
Muscle relaxants
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Serotonin Syndrome:
• Benzodiazepines,
hydration, cooling
• Neuromuscular blockade
• Dantrolene (+/- as
usually rx for neuroleptic
malignant syndrome)
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Serotoninergic stimulation
Hallucinations
Sweating
Tachycardia
Mydriasis
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No true withdrawal state
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Effects last <12 hours
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Treatment
• Supportive
• Reduce stimuli
• Benzos for agitation
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Hallmark SSX: “Visions & Nightmares”
Affects all neurotransmitters:
Dopamine, Adrenergic, Serotonin,
Nicotinic, Histamine
Hallucinogenic properties discovered
when chemist Albert Hofmann
accidentally absorbed LSD through skin
Used for mental disorders such as alcoholism, bipolar,
schizophrenia in 1950’s & 60’s
CIA & MI6 experimented with LSD as mind-control agent
(Project MK-ULTRA)
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Colorless, odorless & mildly bitter
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Supplied in “hits” or “tabs”on blotter
paper , gelatin, or sugar cubes
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Peak effect 4-7 hrs with gradual
decline in effect for next 3-4 hrs
Altered awareness, sense, emotion,
& memories
• Hallucinations of geometric
patterns, trails behind moving
objects & brilliant colors
• Synesthesia: Correspondence
between color, sound & taste; users
“taste” sights & “hear” smells
SSX
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Uterine contractions
Hyperthermia
Erythrema & Goose Bumps
Hyperglycemia
Dry mouth or Salivation
Tachycardia
HTN
Tachypnea
Jaw clenching
Nausea/Vomiting
Diaphoresis
Mydriasis
Sleeplessness
Tremors
TREATMENT
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“Bad trips" most common
adverse reaction
“Flashbacks” also common
with effects lasting long
after drug consumed &
worn off
Episodes may occur weeks,
months or even years
afterward
Treat agitation w/ benzos
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Toxic ingestion 140 uM/L
• >4 grams / 24 hrs
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No specific early symptoms or
signs
Treatment
• Gastric decontamination
• N-acetylcysteine (N-AC)
• Liver transplant
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2% (acute) & 25% (chronic) mortality
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Hallmark symptoms is a mixed acid-base disturbance
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• GI:
N/V, abdominal pain
Reye’s Syndrome (peds)
• CNS:
Tinnitus, lethargy,
seizures, Cerebral
Edema, Irritability
• Pulmonary:
Pulmonary edema (MCC death)
• Heme:
Bleeding abnormalities
Treatment:
• IVF
• Hemodialysis
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GI:
• N/V/D
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Neuro:
• Tremor, seizures
• Vertigo, Coma
• Dysarthria, ataxia,
choreoathetosis
• Hyperreflexia
• Confusion
• Opisthotonis
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Treatment
• Gastric lavage
• Urinary alkalinization & Hemodialysis
• Aminophylline
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Seroquel
Antipsychotics
Alcohol
Heroin
Barbituates
Combinations
Thyroid medications
Inhalants
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Tramadol
Antibiotics
Birth Control Pills
Coumadin & Blood
Thinners
Marijuana
Sleeping pills
Ritalin
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Most common poisoning death
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Vague symptoms related to exposure / dose:
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•

HA & flu-like symptoms
Dizziness
N/V
Irritability, seizures, coma
Cardiovascular collapse
Treatment:
•
•
•
•
Remove from affected area
100% O2
Hyberbaric O2
Treat for co-poisonings (i.e. cyanide)

Hydrogen cyanide ion halts
cellular respiration by
inhibiting an mitochondrial
cytochrome c oxidase
• “Histotoxic hypoxia” as cells unable
to use oxygen

Seizures, apnea, pulmonary
edema, cardiac arrest & death
in mins
•

Lower dosages: LOC, general weakness,
giddiness, headaches, vertigo, confusion
Skin color to turn pink from
cyanide-hemoglobin complexes





Inhaled amyl nitrite, IV sodium nitrite,
IV sodium thiosulfate +/- methemoglobin
Hydroxocobalamin / Cyanokit antidote kits
Vitamin B12 binds cyanide to form harmless cyanocobalamin
form of vitamin B12, then eliminated through urine
Administration of sodium thiosulfate improves ability of the
hydroxocobalamin to detoxify cyanide poisoning
Relatively expensive, not universally available, testing takes
days

Airway control, seizure treatment & supportive management
are key to toxicological emergencies

Rely on physical examination rather than history

Often the exact toxin(s) not known for days, if ever

Poison Control (1-800-222-1222) & Medical Control are your
best resources