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Pesticide. Dr. Suda Vannaprasaht Department of Pharmacology Faculty of Medicine Khon Kaen University, Thailand e-mail: sudvan@kku.ac.th. Pesticides. Insecticide: organophosphates, carbamates, organochlorines, pyrethrins Rodenticide: coumarin, thallium, zinc phosphine

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pesticide

Pesticide

Dr. Suda Vannaprasaht

Department of Pharmacology

Faculty of Medicine

Khon Kaen University, Thailand

e-mail: sudvan@kku.ac.th

pesticides
Pesticides
  • Insecticide: organophosphates, carbamates, organochlorines, pyrethrins
  • Rodenticide: coumarin, thallium, zinc phosphine
  • Herbicide: paraquat, glyphosate
slide3

Organophosphate

Insecticide

  • Parathion
  • Malathion
  • Fenthion
  • Dimethoate
  • Monocrotophos
  • Metamidophos
slide4

Carbamate

Insecticide

  • Carbaryl
  • Carbofuran
  • Propanocarb
  • Thiodicarb
slide5

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
slide6

Organophosphate

Chemical warfare

  • Nerve agents
  • Tabun
  • Sarin
  • Soman
  • VX
slide7

Sarin Gas Attack in Japan

  • June 1994, Matsumoto (614)
  • March 1995, Tokyo subway (5510)
slide8

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
slide11

Muscarinic Receptor

  • = Defecation
  • = Urination
  • = Miosis
  • = Bradycardia
  • = Emesis
  • = Lacrimation
  • = Secretion

D

U

M

B

E

L

S

slide13

Relationship between pupil size and AChE activity in patient exposed to sarin vapor

Intensive Care Med 1997;23:1006

slide15

Investigation

True Cholinesterase (RBC)

Cholinesterase level

Plasma Cholinesterase

management
Management

1. Basic life support

  • Airway
  • Breathing
  • Circulation
slide18

2. Early mangement

    • Prevent absorption:

gastric lavage

activated charcoal

skin decontamination

    • Enhance Elimination
antidote
Antidote

1. Atropine antimuscarinic

Dose: 1- 4 mg IV push every 5-15 min

End point: HR> 60/min or <150/min

pupil size > 3 mm

secretion decrease

pralidoxime 2 pam
Pralidoxime (2-PAM)

Dose: 1-2 gm IV push > 10 min every 2-4 hr.

or IV continuos drip

Max: 1/2 gm/ hr.

Clinical response: Motor power

- tidal volume

- muscle power

slide21

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
slide22

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

slide23

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
slide24

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
slide25

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

slide26

Emergency Department Management

  • Critical Care area

- ABC reminder

- GI decontamination – gastric lavage, activated charcoal

- Antidotes

- Laboratory test: RBC cholinesterase activity

slide27

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

intermediate syndrome
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
slide29

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

organophosphate induce delayed neuropathy opidn
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
slide31

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

slide32

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
slide34

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 Fuller’s earth

slide35

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
slide36

Prehospital Management

  • ABC reminder
  • Antidotes
  • Additional decontamintion
  • Transport to medical facility
slide37

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

slide38

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

slide39

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

slide40

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

slide41

Emergency Department Management

  • - Follow up
  • - severe exposure: CNS sequelae
  • Report
slide44

Organochlorine

DDT

Benzene HC

Cyclodienes

Toxaphene

Lindane**

Aldrin***

Endrin***

Chlordane**

Chlordecone**

Inhalation

Ingestion

Dermal

clinical manifestation
Clinical Manifestation
  • Acute toxicity
    • Seizure threshold & CNS stimulant
  • Respiratory failure
  • 1-2 hr. postingestion
slide46
Ca2+- ATPase neuronal membrane
  • Increase Na+ Channel opening time

tremor

paresthesia

myoclonus

ocular movement

weakness

slide47
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
management1
Management
  • Basic life support
  • Early management
    • Prevent absorption: gastric lavage

activated Charcoal

skin decontamination

  • Support treatment: seizure
slide49

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
slide50

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

slide51

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
slide52

Pre-hospital management

Support zone

  • ABC reminder
  • Additional decontamination
  • Advance treatment
  • Cardiac life support
  • Transport to medical facility
slide53

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

slide54

Emergency Department Management

  • Critical Care area

- ABC reminder

- GI decontamination – gastric lavage, activated charcoal

- No antidotes

- Laboratory

slide55

Emergency Department Management

  • Disposition and Follow- up

- history of serious exposure : admit

- Delay effect : pulmonary edema (Vapor)

- Discharge: asymptomatic

slide57

Paraquat

Herbicides

Diquat

2,4dichlorophenoxyacetic acid

Color : Blue-green

emetic agent

slide58

GSH

GSSG

.

.

O2

O2

OH

Paraquat

Lipid

peroxidation

Lung

Type I and II pneumocyte cell death & alveolitis

Lung fibrosis

slide59

GSH

GSSG

.

.

E

O2

O2

OH

Fe 2+

Low FiO2

F

C

D

Paraquat

Lipid

peroxidation

Lung

A

B

Fuller’s earth, GI decontamination, HD

Paraquat Ab

Type I and II pneumocyte cell death & alveolitis

G

H

Lung fibrosis

paraquat
การดูแลผู้ป่วยที่ได้รับพิษจาก paraquat

O2

2. Prevent absorption

2.1 Gastric lavage

2.2 Fuller’s earth

2.3 MOM 30 ml q 6 hrs

2.4 Skin decontamination

1. Basic life support

slide61
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

slide62
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