module eight: neurotoxicology - acmtmodule eight - neurotoxicology 41 serotonergic hallucinogens •...
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Chemical Agents of Opportunity for Terrorism: TICs & TIMs
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Module Eight: Neurotoxicology
Lewis Nelson, MD, FACMT
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2Module Eight - Neurotoxicology
Course Overview1. Introduction / Principles of Medical Toxicology2. Why Toxic Industrial Chemicals as Terrorist Weapons?3. Inhalation of Toxic Industrial Gases4. Agricultural Chemicals of Concern5. Cyanide and Fumigants6. Psychological Consequences of Mass Chemical Exposure7. Risk Communication8. Neurotoxins9. Water, Food & Medication as Vectors10. Delayed-Onset Toxins11. Post-Event Medical Monitoring12. Tabletop Exercise
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3Module Eight - Neurotoxicology
Please help us improve this course by filling out the module evaluation.
You will receive an email with instructions following the conclusion of
this presentation.
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Faculty Disclosure
• Faculty: Lewis Nelson, MD, FACMT– Relationships with commercial interests:– Speakers Bureau/Honoraria: none – Consulting Fees: none– Other: none
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Participant Question:• How many people are in attendance at your site
(including yourself)?
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Central Nervous System• The CNS is immensely
complex– Great target for terrorism
• The CNS is central to both our function and our thinking
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Objectives• Recognize toxic syndromes that affect the
nervous system– Sedation – Convulsions – Hallucinations
• Describe the unique clinical effects of toxins that cause sedation syndromes
• List examples of chemical agents of opportunity for each toxic syndrome
• Describe initial treatment strategy
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Excitation Inhibition
The Balance of the Brain
• The brain is a fine balance of excitatory and inhibitory influences– Slight alterations in either direction are significant
GlutamateCatecholamines
Gamma-aminobutyric acid(GABA)
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Excitation Inhibition
The Balance of the Brain
• In addition, other neurotransmitters influence our mood, our ability to think, remember, etc.
Modulators of Thought ProcessesSerotonin
AcetylcholineGlutamate
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Clinical Syndromes of the CNS
Too much inhibition = Sedation/coma
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Clinical Syndromes of the CNS
Too much stimulation = Convulsions
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Clinical Syndromes of the CNSAltered Modulation of Thoughts and Sensory Input =
Hallucinations
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Clinical Syndrome: Sedation
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Ethanol Intoxication: A Prototype for Sedative
• Dose-Response The more you drink, the drunker you get– 1 beer: buzz– 3 beers: intoxicated– 6 beers: uncoordinated, slurred speech,
• Disinhibited – 18 beers: coma, respiratory arrest
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Case Study: Moscow Theatre Hostage Crisis (2002)
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Case Study: Moscow Theatre Hostage Crisis (2002)
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Case Study: Moscow Theatre Hostage Crisis (2002)
• Russian Federal Security Service pumped unidentified “gas” into building
• Security forces raided building• 128 of 800 (16%) hostages died
– All but one from gas• All 42 separatists died
– 39-41 from gas
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What happened?
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Characteristics of Opioids
Agent Potency (vs. morphine)
Morphine 1Meperidine 0.5Methadone 4Fentanyl 300Sufentanil 4500Alfentanil 75Remifentanil 220Carfentanil 10,000
Wax PM, Becker CE, Curry SC. Ann Emerg Med 2003;41:700-5.
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Inhaled Sedatives• Aerosolized drugs (dispersed liquids)
– GABAergic agents• Benzodiazepine (e.g. diazepam)• Barbiturate (e.g. pentobarbital)
– Opioids– Ketamine
• Volatile agents– Hydrocarbons
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Sedatives• Suspect whenever patients present with
predominant CNS depression– Dose dependent
• Major complication: RESPIRATORY DEPRESSION– Respiratory depressant effect varies by agent
• Seek specific toxic syndrome: – CNS depression, pinpoint pupils, and respiratory
depression = Opioid– CNS depression, normal examination and vital signs =
Benzodiazepine
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Management of Calmative / Sedative Poisoning• Supportive care
– Ventilation• Antidotes for several
are available– Of limited utility
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Rapid Recognition leads to Urgent Intervention
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Antidotal Treatment Strategy
Excitation Inhibition
Antidote:Naloxone (for opioids)
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Participant Question:
What is the most important treatment for respiratory depression?
a)Artificial ventilationb)Chest compressionsc)Naloxoned)Oxygen
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Clinical Syndrome: Convulsions
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Convulsions
• The brain is a fine balance of excitatory and inhibitory influences– Slight alterations in either direction are significant
• “Inhibition of inhibition” is the most common cause of drug induced seizure
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Inhibition of inhibition
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MMWR 2003;52:199-201
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33Module Eight - Neurotoxicology
Tetramine
• Du-shu-quiang (“very strong poison”)• Used as a rodenticide in China
– Banned in 1984• Like many substances used as rodenticides,
tetramine is highly toxic to humans
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Li et al. BMC Public Health 2014, 14:842
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Some Chemical Causes of Convulsions
• Organophosphate & Carbamate Insecticides• Nicotine• Hydrazines• Camphor• Organochlorines• Strychnine
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Convulsions: Management
• Benzodiazepines• Barbiturates, propofol• Pyridoxine
– Empiric dose, 5 gms (70 mg/kg)
Excitation Inhibition
Antidote:Benzodiazepine
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Participant Question:
Convulsions from chemical toxins are typically due to which one of the following?
a)Hypoglycemiab)Over-stimulation of the brainc)Tetramined)Under-inhibition of the brain
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“Playing with Our Mind”
www.squidy.150m.com
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Hallucinogens
• Alter modulation of thought processes– Serotonergic – Sympathomimetic– Anticholinergic– Anesthetic (PCP and ketamine)
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Serotonergic Hallucinogens• LSD• Tryptamines (DMT, 5-
MeO-DMT, psilocybin)• Ololiuqui (morning glory
seeds)
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Serotonergic Hallucinogens• 1968 - The Yippies (Youth
International Party) • Threatened to “space-out” or
“turn on” the delegates to the Democratic National Convention in Chicago, and everyone else in Chicago as well, by dumping LSD into Lake Michigan.
Maybe just delete this slide?
Abbie Hoffman
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Military Considerations
• Video
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Anticholinergic HallucinogensAtropine, Scopolamine and Hyoscyamine
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Clinical Effects• Mad as a hatter• Red as a beet• Dry as a bone • Hot as Hare• Blind as a bat• Full as a flask(Also decreased GI motility)
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“Modern” History• 1676: a group of men led by Captain John Smith
were sent to Jamestown, Virginia to quell the Bacon rebellion.
• Gathered the plant now known as “Jamestown weed” (or Jimsonweed), Datura stramonium, for a salad.
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1676, Bacon Rebellion:
The soldiers presented a “very pleasant comedy, for they turned natural fools upon it for several days: one would blow a feather in the air; another would dart straws at it with much fury; and another, stark naked, was sitting up in a corner like a monkey, grinning and making mows at them.…. A thousand such simple tricks they played, and after 11 days returned themselves again, not remembering anything that had passed.”
Robert Beverly, The History and Present State of Virginia (1705)
Bacon Rebellion
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July 1995Bosniaks fleeing Srebrenica during the war in Bosnia and Hercegovina.
“Survivors gave consistent descriptions of mortar shells that produced a ‘strange smoke’ of various colors which did not rise but spread out slowly. Following these attacks, some of the marchers - the numbers are unclear - began to hallucinate and behave in an irrational manner, with some even killing their friends or themselves. . . .”
Human Rights Watch
Hay A. Surviving the impossible: the long march from Srebrenica. An investigation of the possible use of chemical warfare agents. Med Confl Surviv 1998;14:120-55.
BZ: 3-Quinuclidinyl benzilate (QNB)
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Anticholinergic Hallucinogens
• Qualitatively similar
Atropine Scopolamine BZ
Dose (70 kg) 8-14 mg 2 mg 0.5 mg
Duration 4-8 h 2-4 h 48-72 h
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Chemical Agents of Opportunity for Terrorism: TICs & TIMs
49Module Eight - Neurotoxicology
Treatment strategy
Antidote:Benzodiazepine
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Chemical Agents of Opportunity for Terrorism: TICs & TIMs
50Module Eight - Neurotoxicology
Participant Question:
Which best describes the clinical effects of hallucinogenic toxins used as terrorist weapons?
a)Incapacitatingb)Lethalc)Sedatingd)Unconcerning
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Chemical Agents of Opportunity for Terrorism: TICs & TIMs
51Module Eight - Neurotoxicology
Concluding Thoughts
• The CNS is a unique target organ for terrorism• Limited number of acute clinical consequences• Management is generally symptomatic although
“antidotes” may be available for certain agents.
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Chemical Agents of Opportunity for Terrorism: TICs & TIMs
52Module Eight - Neurotoxicology
Questions?