Pesticide Dr. Suda Vannaprasaht Department of Pharmacology

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Pesticide

• Dr. Suda Vannaprasaht
• Department of Pharmacology
• Faculty of Medicine
• Khon Kaen University, Thailand
• e-mail sudvan_at_kku.ac.th

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Pesticides

• Insecticide organophosphates, carbamates,
  organochlorines, pyrethrins
• Rodenticide coumarin, thallium, zinc phosphine
• Herbicide paraquat, glyphosate

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Organophosphate
Insecticide

• Parathion
• Malathion
• Fenthion
• Dimethoate
• Monocrotophos
• Metamidophos

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Carbamate
Insecticide

• Carbaryl
• Carbofuran
• Propanocarb
• Thiodicarb

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Route of exposure

• Inhalation unlikely at ordinary temperatures,
  low volatility
• sprays or dusts
• hydrocarbon solvent (toluene or xylene)
• Skin/eye contact not irritate skin or eye
• rapidly absorbed through intact skin and
  eyes, contributing to systemic toxicity
• Ingestion acute toxicity and rapidly fatal
  systemic poisoning

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Organophosphate
Chemical warfare

• Nerve agents
• Tabun
• Sarin
• Soman
• VX

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Sarin Gas Attack in Japan

• June 1994, Matsumoto (614)
• March 1995, Tokyo subway (5510)

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Sarin toxicology

• Isopropyl methylphosphonofluoridate
• High potency organophosphate ester
• Clear, colorless liquid with a vapor pressure of
  2.1 mm Hg
• Liquid rapidly penetrate skin and clothing
• Vapor rapidly penetrate mucous membranes of the
  eye or inhaled in to the lung

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Mechanism of Intoxication
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Muscarinic Receptor
Defecation Urination Miosis Bradycardia
Emesis Lacrimation Secretion
D U M B E L S
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JAMA 2003290661
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Relationship between pupil size and AChE activity
in patient exposed to sarin vapor
Intensive Care Med 1997231006
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Intensive Care Med 1997231006
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Investigation
True Cholinesterase (RBC)
Cholinesterase level
Plasma Cholinesterase
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Comparison between RBC and plasma AchE
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Management

• 1. Basic life support
• Airway
• Breathing
• Circulation

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• 2. Early mangement
• Prevent absorption
• gastric lavage
• activated charcoal
• skin decontamination
• Enhance Elimination

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Antidote

• 1. Atropine antimuscarinic

Dose 1- 4 mg IV push every 5-15 min
End point HRgt 60/min or lt150/min pupil size
gt 3 mm secretion decrease
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Pralidoxime (2-PAM)
Dose 1-2 gm IV push gt 10 min every 2-4 hr. or
IV continuos drip Max 1/2 gm/ hr.
Clinical response Motor power - tidal
volume - muscle power
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Parathion
Pre-hospital management
Hot zone

• Rescuer Protection Highly toxic systemic poison
• absorbed well by all routes of exposure
• - Respiratory protection Positive pressure,
  self contained breathing apparatus (SCBA)
• - Skin protection Chemical protective clothing
• ABC Reminder
• Victim removal

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Pre-hospital management
Decontamination zone

• Rescuer Protection lower level of protection
  than that worn in Hot Zone
• ABC Reminders
• Basic Decontamination
• - Rapid and thorough decontamination is
  critical, but must proceed concurrently with
  supportive and antidotal measure
• - Quickly remove and double- bag contaminated
  clothing and personal belonging

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Pre-hospital management

• Wash repeatedly with copious amounts of soap and
  water
• Rescuers wear rubber gloves as vinyl groves
• Clean hair, fingernails and skin folds
• Irrigate exposed or irritated eyes with plain
  water or saline for 15 min
• Activated charcoal
• Not induce emesis
• Transfer to support zone

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Pre-hospital management
Support zone

• Support zone team wear disposable aprons or
  gowns and rubber gloves for protection
• ABC reminder
• Additional decontamination
• Advance treatment
• Antidotes
• Transport to medical facility

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Emergency Department Management

• Decontamination area
• - Butyl rubber aprons and butyl rubber gloves
• - Two layers of latex gloves and waterproof
  apron or chemical resistant jumpsuit
• - Wash hand
• - ABC reminder
• - Basic decontamination

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Emergency Department Management

• Critical Care area
• - ABC reminder
• - GI decontamination gastric lavage, activated
  charcoal
• - Antidotes
• - Laboratory test RBC cholinesterase activity

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Emergency Department Management

• Disposition and Follow- up
• - Life threatening illness, serious exposure and
  symptomatic
• - Delay effect skin absorption
• aspiration of chemical (hydrocarbon) ?
  chemical pneumonitis
• Chronic neurologic symptoms

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Intermediate Syndrome

• 1- 4 days after acute poisoning
• Sign cranial nerve palsy
• paralysis of proximal limb muscle, neck muscle
  respiratory
• Fenthion, monocrotophos, dimethoate,
  methamidophos etc.
• DDx redistribution of organophosphate
• Treatment supportive

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Emergency Department Management
- Patient release asymptomatic for 4-6 hours
after exposure - Follow up primary care
physician persistant CNS sequelae and
delayed peripheral neuropathy - Report
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Organophosphate induce delayed neuropathy (OPIDN)

• After 2- 4 wks after acute poisoning
• Delay neuropathy cramping muscle pain
• distal numbness paresthesia
• progressive leg weakness and gait disturbance
• depressed deep tendon reflexes
• lower then upper extremeties

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Nerve agent
Prehospital Management
Hot zone

• Rescuer Protection rapidly absorbed by
  inhalation and ocular contact
• rapid local and systemic effect
• liquid is readily absorbed thorough skin
  (delay for minutes to up to 18 hours)
• - Respiratory protection Pressure demand,
  self-contained breathing apparatus
• - Skin protection chemical-protective clothing
  and butyl rubber gloves

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Prehospital Management

• ABC reminders
• There are 4 triage categories
• Antidote difficult to achieve in Hot Zone
• Victim removal decontamination zone

Decontamination zone

• Rapid decontamination is critical to prevent
  further absorption
• Rescuer protection wear the same level of
  protection as required in the Hot Zone

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Triage for nerve agent casualties
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Prehospital Management

• ABC reminder
• Antidotes
• Basic decontamination
• Liquid - eyes decontamination within minutes of
  exposure
• - flush eyes with water for 5-10 minutes
• - remove all clothing and wash skin with soap
  and water
• - 0.5 sodium hypochlorite
• - absorbent powder such as flour, talcum powder
  or Fullers earth

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Prehospital Management

• - Place contaminated clothes and personal
  belonging in a sealed double bag
• Vapor - no need to flush eyes following
  exposure
• Ingestion activated charcoal
• Transfer to support zone

Support zone

• Victims must be decontamination properly before
  entering the Support Zone

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Prehospital Management

• ABC reminder
• Antidotes
• Additional decontamintion
• Transport to medical facility

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Emergency Department Management

• Decontamination Area
• - ABC reminder
• - Personal protection
• - before enter the facility
• - inside the hospital negative air pressure
  and floor drain to contain contamination
• - personal wear the same level of protection
  require in Hot Zone
• - Basic decontamination

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Emergency Department Management

• Treatment area
• - ABC reminder
• - Triage conscious and full muscular control
  need minimal care
• - exposed to liquid observe at least 18 hours
• - only exposure to vapor no sign of exposure
  by the time reach the hospital ? discharge

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Emergency Department Management
- Antidotes Vapor exposure - Miosis and
rhinorrhea need no care a) eye pain or head
pain or nausea and vomiting ? topic
atropine b) rhinorrhea is very severe ? atropin
IM 2 mg
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Emergency Department Management

• - Laboratory test RBC AChE
• Disposition and Follow up
• - Vapor agent miosis and/or mild rhinorrhea ?
  do not need to admit
• - All other patients hospitalized and observed
  closely
• - Delay effect
• - skin exposure 18 hours
• - inhalation 12 hours ( bronchitis, pneumonia,
  pulmonary edema, respiratory failure

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Emergency Department Management

• - Follow up
• - severe exposure CNS sequelae
• Report

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Organochlorine poisoning
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Organochlorine
DDT
Benzene HC
Cyclodienes
Toxaphene
Lindane
Aldrin Endrin Chlordane Chlordecone
Inhalation
Ingestion
Dermal
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Clinical Manifestation

• Acute toxicity
• Seizure threshold CNS stimulant

• Respiratory failure
• 1-2 hr. postingestion

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• Ca2- ATPase neuronal membrane
• Increase Na Channel opening time

tremor
paresthesia
myoclonus
ocular movement
weakness
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• Chronic toxicity
• Chlordecone factory workers who prolong
  exposured
• pseudotumor cerebri
• oligospermia decrease sperm motility
• wt loss, tremor weakness, ataxia
• metal status change,
• abn liver function test
• Carcinogen

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Management

• Basic life support
• Early management
• Prevent absorption gastric lavage
• activated Charcoal
• skin decontamination
• Support treatment seizure

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Chlordane
Pre-hospital management
Hot zone

• Rescuer Protection Moderate toxic systemic
  poison
• absorbed well by all routes of exposure
• - Respiratory protection Positive pressure,
  self contained breathing apparatus (SCBA)
• - Skin protection Chemical protective clothing
• ABC Reminder
• Victim removal

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Pre-hospital management
Decontamination zone

• Rescuer Protection lower level of protection
  than that worn in Hot Zone
• ABC Reminders
• Basic Decontamination
• - Quickly remove and double- bag contaminated
  clothing and personal belonging

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Pre-hospital management

• Flush with water 20 min then wash with soap
  twice
• Do not scrub
• Irrigate exposed or irritated eyes with water or
  saline for 20 min
• Activated charcoal
• Not induce emesis
• Transfer to support zone

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Pre-hospital management
Support zone

• ABC reminder
• Additional decontamination
• Advance treatment
• Cardiac life support
• Transport to medical facility

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Emergency Department Management

• Decontamination area
• - Telfon gloves and suits before treating
  patient
• - Flush with water 20 min then wash with soap
  twice
• - ABC reminder
• - Basic decontamination

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Emergency Department Management

• Critical Care area
• - ABC reminder
• - GI decontamination gastric lavage, activated
  charcoal
• - No antidotes
• - Laboratory

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Emergency Department Management

• Disposition and Follow- up
• - history of serious exposure admit
• - Delay effect pulmonary edema (Vapor)
• - Discharge asymptomatic

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Paraquat Toxicity
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Paraquat
Herbicides
Diquat
2,4dichlorophenoxyacetic acid
Color Blue-green emetic agent
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GSH
GSSG
.
.
O2
O2
OH
Paraquat
Lipid peroxidation
Lung
Type I and II pneumocyte cell death alveolitis
Lung fibrosis
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GSH
GSSG
.
.
E
O2
O2
OH
Fe 2
F
Low FiO2
C
D
Paraquat
Lipid peroxidation
Lung
A
B
Fullers earth, GI decontamination, HD
Paraquat Ab
Type I and II pneumocyte cell death alveolitis
G
H
Lung fibrosis
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????????????????????????????? paraquat
O2
1. Basic life support

• 2. Prevent absorption
• 2.1 Gastric lavage
• 2.2 Fullers earth
• 2.3 MOM 30 ml q 6 hrs
• 2.4 Skin decontamination

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• 3. Increase elimination
• 3.1 Hemodialysis/ Hemoperfusion
• 4. Modification of tissue toxicities
• 4.1 Modulate inflammatory responses
• - Cyclophosphamide 5mg/kg/day IV divided to
  every 8 hr
• - Dexamethazone 10 mg IV q 8 hr
• - Chlorpheniramine 4 mg 1 tab po qid

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• 4.2 Prevent oxidation
• - Vit C (500mg/amp) 6 g/day IV
• - Vit E (400 i.u./ tab) 2 tabs qid
• - N-acetylcysteine (300mg/amp) 50mg/kg
  every 8 hr

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