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Pesticide
Dr. Suda VannaprasahtDepartment of Pharmacology
Faculty of MedicineKhon Kaen University, Thailand
e-mail: [email protected]
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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