NERVE AGENTS

1
NERVE AGENTS
2
DEFINITION

• A substance that causes biological effects by
  inhibiting acetylcholinesterase
• Acetylcholine accumulates
• Effects are due to excess acetylcholine

3
EXAMPLES

• Carbamates
• Physostigmine (Antilirium)
• Neostigmine (Prostigmine)
• Pyridostigmine (Mestinon)
• Sevin (insecticide)
• Organophosphates
• Malathion
• Diazinon
• Nerve Agents

4
NERVE AGENTS

• GA (Tabun)
• GB (Sarin)
• GD (Soman)
• GF
• VX

5
GB
6
VX
7
PHYSICAL PROPERTIES

• Clear, colorless liquids (when fresh), not nerve
  gas
• Tasteless, most are odorless
• Freeze/melt lt0º C
• Boil gt150º C
• Volatility GBgtGDgtGAgtGFgtgtVX
• Penetrate skin, clothing

8
TOXICITY

• LCt50
  LD50
• mg-min/m3
  mg/70kg
• GA 400 1,000
• GB 100 1,700
• GD 70 50
• GF 50 30
• VX 10 10

9
LD50 of VX
10
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

11
NERVE TRANSMISSIONNERVE TO NERVE
12
NERVE TRANSMISSIONNERVE TO SKELETAL MUSCLE
13
NERVE TRANSMISSIONNERVE TO SMOOTH MUSCLE
14
NERVE TRANSMISSIONNERVE TO EXOCRINE GLAND
15
IMPULSE TERMINATIONTHE ROLE OF ACHE
16
PHYSIOLOGY NERVE AGENT

• Enzyme (AChE) is inhibited
• Does not destroy ACh
• Excess ACh continues to stimulate organ
• Organ overstimulation

17
EXPOSURE TO NERVE AGENT
18
EFFECTS ON STRIATED (SKELETAL) MUSCLE
19
EFFECTS ON SMOOTH ANDCARDIAC MUSCLE
20
EFFECTS ON EXOCRINE GLANDS
21
TWO MAJOR TYPES OFCHOLINERGIC RECEPTORS

• Muscarinic
• Smooth muscles
• Exocrine glands
• Cranial nerves (vagus)
• Nicotinic
• Skeletal muscles
• Pre-ganglionic nerves
• Both
• CNS

22
CHOLINERGIC MUSCARINIC EFFECTS

• Muscarinic
• Smooth muscles
• Airways - constrict
• GI tract - constrict
• Pupils - constrict
• Glands
• Eyes, nose, mouth, sweat, airways, GI
• Heart, bradycardia (vagal)

23
CHOLINERGIC NICOTINIC EFFECTS

• Skeletal muscles
• Fasciculations, twitching, fatigue, flaccid
  paralysis
• Pre-ganglionic
• Tachycardia, hypertension

24
ACh at RECEPTORS
Nicotinic
Nicotinic
Preganglionicsynapses in ANS Skeletal muscle
Muscarinic
Muscarinic
Synapses in CNS Smooth muscle Exocrine glands
25
HEART RATE VARIABLE

• Muscarinic (vagal) decreases ( )
• Nicotinic (ganglionic) increases ( )
• Hypoxia decrease oxygen ( )
• May be high, low, normal ( )

26
CENTRAL NERVOUS SYSTEM (CNS)

• Acute, large exposure to nerve agent
• Loss of consciousness
• Seizures
• Apnea
• Death

27
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

28
CNS

• Minor CNS effects
• May last for 3 to 6 weeks
• May follow any exposure
• Not always present
• Very slight, subtle

29
VAPOR

• Small exposure
• Eyes Miosis injection dim, blurred
  vision pain maybe nausea, vomiting
• Nose Rhinorrhea
• Mouth Salivation
• Airways Shortness of breath

30
VAPOR - RESPIRATORY TRACT

• Small exposure
• Tight chest
• Moderate exposure
• Severe breathing difficulty
• Gasping, irregular breathing
• Compounded by excessive secretions

31
VAPOR - GASTROINTESTINAL

• Exposure to a large but not lethal concentration
  may cause
• Nausea, vomiting
• Pain in abdomen
• Diarrhea, involuntary defecation or urination

32
VAPOR

• Large exposure
• Previously listed effects plus...
• Loss of consciousness
• Seizures
• Apnea
• Flaccid paralysis
• Death

33
VAPOR

• Onset of effects seconds to minutes
• After removal from vapor
• Effects do not worsen
• May improve
• No late-onset effects

34
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

35
LIQUID ON SKIN

• Onset of effects
• Small, medium drop
• As long as 18 hours
• Large, lethal drop
• Usually lt30 minutes

36
LIQUID ON SKIN

• Effects may occur despite initial decontamination
• Effects may worsen

37
MIOSIS

• Almost always after vapor
• After liquid on skin
• Small no
• Moderate maybe
• Severe yes

38
PHOTO OF NORMAL PUPIL RESPONSE
39
PHOTO OF PINPOINT PUPIL
40
NERVE AGENT EFFECTS - EYES
3 6 13 20 41 62
Days after exposure
41
MANAGEMENT

• ABCs
• Drugs (nerve agent antidotes)
• Decontamination
• Supportive
• Anticonvulsant therapy
• Not necessarily in this order!

42
MANAGEMENT

• MOST IMPORTANT
• Protect self
• Protective gear
• Decontaminate casualty
• Protect medical facility
• Decontaminate casualty

43
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

44
VENTILATION

• Possibly less need after pyridostigmine
• None forward of Battalion Aid Station
• Very high airway resistance until atropine is
  given

45
ANTIDOTES

• Too much acetylcholine
• Block excess acetylcholine
• Enzyme inhibited
• Reactivate enzyme

46
ATROPINE

• A cholinergic blocking drug
• An anticholinergic
• Blocks excess acetylcholine
• Clinical effects at muscarinic sites
• Dries secretions
• Reduces smooth muscle constriction

47
ATROPINE at RECEPTORS
48
ACH AND ATROPINE at RECEPTORS
49
ATROPINE

• 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

50
ATROPINE

• Not for
• Skeletal muscle effects
• Miosis, unless used topically
• Use will cause blurred vision for 24 hours

51
ACTION OF ATROPINE ONSMOOTH MUSCLE
52
EFFECTS ON EXOCRINE GLANDS
53
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)

54
OXIMES

• Effects at nicotinic sites
• Increase skeletal muscle strength
• No clinical effects at muscarinic sites

55
ACTION OF PRALIDOXIME CHLORIDE(2-PAM Cl)
56
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

57
AGING OF THE NERVE AGENT-ACHE COMPLEX
58
OXIMES

• Other countries have different ones
• England P2S
• Some European countries obidoxime
• Israel TMB4
• Japan 2-PAMI

59
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

60
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

61
RECOVERY

• Severe casualty
• Without complications, conscious, breathing, in
  2 to 3 hours

62
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

63
MARK I AUTO-INJECTOR
64
MILD VAPOR EXPOSURE

• Miosis, rhinorrhea
• Rx Probably none unless rhinorrhea is severe
• Atropine IM will not help miosis

65
MODERATE VAPOR EXPOSURE

• Miosis, rhinorrhea, moderate or severe dyspnea
• Walking and talking
• Rx 1 MARK I(if dyspnea is quite severe 2 MARK
  Is)

66
SEVERE VAPOR EXPOSURE

• Unconscious, or
• Seizing or post-ictal, or
• Clinical effects in two or more systems(airway,
  GI, muscular, CNS)

67
SEVERE VAPOR EXPOSURE

• Rx 3 MARK Is and diazepam ASAP
• Ventilation
• Rx even after cardiac arrest

68
MILD LIQUID EXPOSURE

• Localized twitching, sweating
• Rx 1 MARK I (agent has been absorbed)

69
MODERATE SKIN EXPOSURE

• GI effects vomiting, diarrhea, cramps
• Rx 1 MARK I
• Watch carefully for 18 hours

70
SEVERE SKIN EXPOSURE

• Unconscious, or
• Seizing or post-ictal, or
• Clinical effects in two or more systems(airway,
  GI, muscular, CNS)

71
SEVERE SKIN EXPOSURE

• Rx 3 MARK Is and diazepam
• Ventilation
• Rx after cardiac arrest

72
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