Pesticide

Dr. Suda VannaprasahtDepartment of Pharmacology

Faculty of MedicineKhon Kaen University, Thailand

e-mail: sudvan@kku.ac.th

Pesticides

Insecticide: organophosphates, carbamates,

organochlorines, pyrethrins

Rodenticide: coumarin, thallium, zinc phosphine

Herbicide: paraquat, glyphosate

Organophosphate

Insecticide

• Parathion

• Malathion

• Fenthion

• Dimethoate

• Monocrotophos

• Metamidophos

Carbamate

Insecticide

• Carbaryl

• Carbofuran

• Propanocarb

• Thiodicarb

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

Organophosphate

Chemical warfareNerve agents

• Tabun

• Sarin

• Soman

• VX

Sarin Gas Attack in Japan

• June 1994,

Matsumoto (614)

• March 1995,

Tokyo subway (5510)

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

Mechanism of Intoxication

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

DUMBELS

Muscarinic Receptor

JAMA 2003;290:661

Intensive Care Med 1997;23:1006

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

Intensive Care Med 1997;23:1006

True Cholinesterase (RBC)

Investigation

Cholinesterase level

Plasma Cholinesterase

RBC AchE Plasma AchE

AdvantagesBetter reflection of synaptic

inhEasier to assay, decline

faster

SiteCNS gray matter, RBC,

Motor endplateCNS white matter, plasma,

liver, heart, pancrease

Regeneration 1%/day 25-30% in first 7-10 days

Normalization 5-7 wks 28-42 days

2-PAM response Normalizes Slight increase

UseAcute exposure, response to

treatmentAcute exposure

False depression

Pernicious,hemoglobinopathies,

antimalaria treatment,oxalate blood tube

Cirrhosis, malnutrition,hypersensitivity reaction,

drugs(succinylcholine,codeine, morphine), genetic

deficiency

Comparison between RBC and plasma AchE

Management

1. Basic life support

Airway

Breathing

Circulation

2. Early mangement Prevent absorption:

gastric lavage

activated charcoal

skin

decontamination

Enhance Elimination

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

pupil size > 3 mm

secretion decrease

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

Antidote

1. Atropine antimuscarinic

Clinical response: Motor power

- tidal volume

- muscle power

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

or IV continuos drip

Max: 1/2 gm/ hr.

Pralidoxime (2-PAM)

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

Parathion

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

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

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

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

Emergency Department Management

Critical Care area

- ABC reminder

- GI decontamination – gastric lavage, activated charcoal

- Antidotes

- Laboratory test: RBC cholinesterase activity

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

• 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

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)

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

Nerve agent

Prehospital ManagementHot 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

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

Prehospital Management

Triage for nerve agent casualties

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

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

Prehospital Management

Support zone

Victims must be decontamination properly before entering the Support Zone

Prehospital Management

ABC reminder

Antidotes

Additional decontamintion

Transport to medical facility

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

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

Emergency Department Management

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

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

Emergency Department Management

- Follow up

- severe exposure: CNS sequelae

Report

Organochlorine poisoning

Organochlorine

DDT Benzene HCCyclodienesToxaphene

Lindane** Aldrin***

Endrin***

Chlordane**

Chlordecone**

Inhalation Ingestion Dermal

Clinical Manifestation

Acute toxicity Seizure threshold & CNS stimulant

Respiratory failure

1-2 hr. postingestion

Ca2+- ATPase neuronal membrane

Increase Na+ Channel opening time

tremor paresthesia myoclonus ocular movement weakness

Chronic toxicity

Chlordecone: factory workers who prolong expo

sured

• pseudotumor cerebri

• oligospermia & decrease sperm motility

• wt loss, tremor weakness, ataxia

• metal status change,

• abn liver function test

Carcinogen

Management

Basic life support

Early management

Prevent absorption: gastric lavage

activated Charcoal

skin decontamination

Support treatment: seizure

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

Chlordane

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

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

Pre-hospital management

Support zone

ABC reminder

Additional decontamination

Advance treatment

Cardiac life support

Transport to medical facility

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

Emergency Department Management

Critical Care area

- ABC reminder

- GI decontamination – gastric lavage, activated charcoal

- No antidotes

- Laboratory

Emergency Department Management

Disposition and Follow- up

- history of serious exposure : admit

- Delay effect : pulmonary edema (Vapor)

- Discharge: asymptomatic

Herbicides

Paraquat

Diquat

2,4dichlorophenoxyacetic acid

Color : Blue-greenemetic agent

Paraquat Lung

O2 O2

.OH.

Lipid peroxidation

Type I and II pneumocyte cell death & alveolitis

Lung fibrosis

GSH GSSG

Paraquat Lung

O2 O2

.OH.

Lipid peroxidation

Type I and II pneumocyte cell death & alveolitis

Lung fibrosis

A

C D

B

GSH GSSGE

F

G

Fuller’s earth, GI decontamination,

HD

Paraquat Ab

Low FiO2Fe 2+

H

การดู�แลผู้�ป่�วยที่��ไดูร�บพิ�ษจาก paraquat

2. Prevent absorption

2.1 Gastric lavage

2.2 Fuller’s earth

2.3 MOM 30 ml q 6 hrs

2.4 Skin decontamination

O2

1. Basic life support

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

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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