Transcript No Slide Title

NERVE AGENTS
DEFINITION
 A substance that causes biological effects
by inhibiting acetylcholinesterase
 Acetylcholine accumulates
 Effects are due to excess acetylcholine
EXAMPLES
 Carbamates
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Physostigmine (Antilirium)
Neostigmine (Prostigmine)
Pyridostigmine (Mestinon)
Sevin (insecticide)
 Organophosphates
 Malathion
 Diazinon
 “Nerve Agents”
NERVE AGENTS





GA (Tabun)
GB (Sarin)
GD (Soman)
GF
VX
GB
CH3
O
CH3
P
F
O
CH
CH3
VX
CH3
O
P
CH3CH2O
CH(CH3)2
S
CH2CH2
N
CH(CH3)2
PHYSICAL PROPERTIES
 Clear, colorless liquids (when fresh), not
“nerve gas”
 Tasteless, most are odorless
 Freeze/melt <0º C
 Boil >150º C
 Volatility GB>GD>GA>GF>>VX
 Penetrate skin, clothing
TOXICITY
GA
GB
GD
GF
VX
LCt50
LD50
mg-min/m3
mg/70kg
400
100
70
50
10
1,000
1,700
50
30
10
LD50 of VX
PHYSIOLOGY: NORMAL
 Electrical impulse goes down nerve
 Impulse causes release of neurotransmitter,
acetylcholine (Ach)
 ACh stimulates receptor site on organ
 Causes organ to act
 ACh is destroyed by AChE
(Acetylcholinesterase)
 No more organ activity
NERVE TRANSMISSION:
NERVE TO NERVE
NERVE TRANSMISSION:
NERVE TO SKELETAL MUSCLE
NERVE TRANSMISSION:
NERVE TO SMOOTH MUSCLE
NERVE TRANSMISSION:
NERVE TO EXOCRINE GLAND
IMPULSE TERMINATION:
THE ROLE OF ACHE
PHYSIOLOGY: NERVE AGENT


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
Enzyme (AChE) is inhibited
Does not destroy ACh
Excess ACh continues to stimulate organ
Organ overstimulation
EXPOSURE TO NERVE AGENT
EFFECTS ON STRIATED (SKELETAL)
MUSCLE
EFFECTS ON SMOOTH AND
CARDIAC MUSCLE
EFFECTS ON EXOCRINE GLANDS
TWO MAJOR TYPES OF
CHOLINERGIC RECEPTORS
 Muscarinic
 Smooth muscles
 Exocrine glands
 Cranial nerves (vagus)
 Nicotinic
 Skeletal muscles
 Pre-ganglionic nerves
 Both
 CNS
CHOLINERGIC MUSCARINIC EFFECTS
 Muscarinic
 Smooth muscles
 Airways - constrict
 GI tract - constrict
 Pupils - constrict
 Glands
 Eyes, nose, mouth, sweat, airways, GI
 Heart, bradycardia (vagal)
CHOLINERGIC NICOTINIC EFFECTS
 Skeletal muscles
 Fasciculations, twitching, fatigue, flaccid
paralysis
 Pre-ganglionic
 Tachycardia, hypertension
ACh at RECEPTORS
Nicotinic
Nicotinic
Preganglionic
synapses in ANS
ACh
ACh
Skeletal muscle
Muscarinic
Muscarinic
Synapses in CNS
ACh
Smooth muscle
Exocrine glands
ACh
HEART RATE VARIABLE
 Muscarinic (vagal) decreases (
)
 Nicotinic (ganglionic) increases (
 Hypoxia: decrease oxygen (
 May be high, low, normal (
)
)
)
CENTRAL NERVOUS SYSTEM (CNS)
 Acute, large exposure to nerve agent
 Loss of consciousness
 Seizures
 Apnea
 Death
CNS
 Acute, small exposure to nerve agent
 Minor CNS effects
 Slowness in thinking and decision making
 Sleep disturbances
 Poor concentration
 Emotional problems
 Other minor problems
CNS
 Minor CNS effects
 May last for 3 to 6 weeks
 May follow any exposure
 Not always present
 Very slight, subtle
VAPOR
 Small exposure
 Eyes: Miosis; injection; dim,
blurred vision; pain;
maybe nausea, vomiting
 Nose: Rhinorrhea
 Mouth: Salivation
 Airways: Shortness of breath
VAPOR - RESPIRATORY TRACT
 Small exposure
 Tight chest
 Moderate exposure
 Severe breathing
difficulty
 Gasping, irregular
breathing
 Compounded by
excessive
secretions
VAPOR - GASTROINTESTINAL
 Exposure to a large
but not lethal
concentration may
cause:
 Nausea, vomiting
 Pain in abdomen
 Diarrhea,
involuntary
defecation or
urination
VAPOR
 Large exposure
 Previously listed effects plus...
 Loss of consciousness
 Seizures
 Apnea
 Flaccid paralysis
 Death
VAPOR
 Onset of effects: seconds to minutes
 After removal from vapor
 Effects do not worsen
 May improve
 No late-onset effects
LIQUID ON SKIN
 Small droplet: local effects
 Sweating, fasciculations
 Medium droplet: systemic effects
 GI
 Large droplet: pulmonary and CNS
 Respiratory distress, apnea, death
 Loss of consciousness, seizures, apnea,
flaccid paralysis, death
LIQUID ON SKIN
 Onset of effects
 Small, medium drop
 As long as 18 hours
 Large, lethal drop
 Usually <30 minutes
LIQUID ON SKIN
 Effects may occur despite initial
decontamination
 Effects may worsen
MIOSIS
 Almost always after vapor
 After liquid on skin:
 Small: no
 Moderate: maybe
 Severe: yes
PHOTO OF NORMAL PUPIL RESPONSE
PHOTO OF PINPOINT PUPIL
Days after exposure
NERVE AGENT EFFECTS - EYES
3
6
13
20
41
62
MANAGEMENT
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ABCs
Drugs (nerve agent antidotes)
Decontamination
Supportive
Anticonvulsant therapy

Not necessarily in this order!
MANAGEMENT
 MOST IMPORTANT
 Protect self
 Protective gear
 Decontaminate casualty
 Protect medical facility
 Decontaminate casualty
SKIN DECONTAMINATION
 Early is best, within 1 to 2 minutes
 Little benefit after 30 minutes
 Physical removal is best
 Forceful flush with water
 Stick, dirt, cloth, M291
 Solutions (hypochlorite, etc.)
 Detoxify after many minutes
VENTILATION
 Possibly less need after pyridostigmine
 None forward of Battalion Aid Station
 Very high airway resistance until atropine is
given
ANTIDOTES
 Too much acetylcholine
 Block excess acetylcholine
 Enzyme inhibited
 Reactivate enzyme
ATROPINE
 A cholinergic blocking drug
 An anticholinergic
 Blocks excess acetylcholine
 Clinical effects at muscarinic sites
 Dries secretions
 Reduces smooth muscle constriction
ATROPINE at RECEPTORS
ACH AND ATROPINE at RECEPTORS
ATROPINE
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Side effects in unexposed
Starting dose 2 mg or 6 mg
More, 2 mg every 5 to 10 minutes
Until
 Secretions drying
 Ventilation improved
 Usual dose: (severe casualty) 15 to 20 mg
 1000s of mgs in insecticide
ATROPINE
 Not for
 Skeletal muscle effects
 Miosis, unless used topically
 Use will cause blurred vision for 24
hours
ACTION OF ATROPINE ON
SMOOTH MUSCLE
EFFECTS ON EXOCRINE GLANDS
STOPPING ATROPINE
 Endpoints
 Reduction in secretions (muscarinic effects)
 Reduction in chest tightness (muscarinic effects)
 Patient able to breathe comfortably on his/her own
 Do not titrate to
 Heart rate (variable; not an indicator of severity of
exposure)
 Miosis (may persist for up to 6 weeks despite
atropine)
 Twitching or fasciculations (nicotinic effects)
OXIMES
 Effects at nicotinic sites
 Increase skeletal muscle strength
 No clinical effects at muscarinic sites
ACTION OF PRALIDOXIME CHLORIDE
(2-PAM Cl)
OXIMES
 Remove agent from enzyme, unless aging has
occurred
 Aging: agent-enzyme complex changes
 Oximes cannot reactivate enzyme
 Aging times: GD 2 min
GB 3 to 4 hours
Others longer
AGING OF THE NERVE AGENTACHE COMPLEX
OXIMES
 Other countries have different ones
 England: P2S
 Some European countries: obidoxime
 Israel: TMB4
 Japan: 2-PAMI
2-PAM Cl DOSE
 NAAK (MARK I): contains 600 mg
 One or three Combopens; repeat in one hour
 IV: One gram slowly (20 to 30 min)
 Repeat in one hour
SEIZURES
 Without pyridostigmine
 Not prolonged
 Anticonvulsant seldom necessary
 Prolonged after pyridostigmine
 Possible brain damage from prolonged
seizures
 Anticonvulsant needed (diazepam)
 Give diazepam to any severe casualty
RECOVERY
 Severe casualty:
 Without complications, conscious,
breathing, in 2 to 3 hours
RETURN TO DUTY
 Dose-dependent, need dependent
 Could be hours with minor exposure, great
need
 Many days after severe exposure
 Consider:
 Vision
 Minor, subtle mental effects
MARK I AUTO-INJECTOR
MILD VAPOR EXPOSURE
 Miosis, rhinorrhea
 Rx: Probably none unless rhinorrhea is
severe
 Atropine IM will not help miosis
MODERATE VAPOR EXPOSURE
 Miosis, rhinorrhea, moderate or severe
dyspnea
 Walking and talking
 Rx: 1 MARK I
(if dyspnea is quite severe: 2 MARK Is)
SEVERE VAPOR EXPOSURE
 Unconscious, or
 Seizing or post-ictal, or
 Clinical effects in two or more systems
(airway, GI, muscular, CNS)
SEVERE VAPOR EXPOSURE
 Rx: 3 MARK Is and diazepam ASAP
 Ventilation
 Rx even after cardiac arrest
MILD LIQUID EXPOSURE
 Localized twitching, sweating
 Rx: 1 MARK I (agent has been absorbed)
MODERATE SKIN EXPOSURE
 GI effects: vomiting, diarrhea, cramps
 Rx: 1 MARK I
 Watch carefully for 18 hours
SEVERE SKIN EXPOSURE
 Unconscious, or
 Seizing or post-ictal, or
 Clinical effects in two or more systems
(airway, GI, muscular, CNS)
SEVERE SKIN EXPOSURE
 Rx: 3 MARK Is and diazepam
 Ventilation
 Rx after cardiac arrest
NERVE AGENTS: SUMMARY
 Highly toxic, rapid acting
 Convert acetylcholine into a poison; create
cholinergic crisis
 Treatable with specific therapy
 Therapy must be timely (FAST!) and may be
life-saving