PDP 406 CLINICAL TOXICOLOGY
Pharm.D
Fourth Year
Pesticide
Mr.D.Raju.M.Pharm.,
Lecturer
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 warfare
Nerve 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
Muscarinic Receptor
D = Defecation
U = Urination
M = Miosis
B = Bradycardia
E = Emesis
L = Lacrimation
S = Secretion
JAMA 2003;290:661
Relationship between pupil size and AChE
activity in patient exposed to sarin vapor
Intensive Care Med 1997;23:1006
Intensive Care Med 1997;23:1006
Investigation
True Cholinesterase (RBC)
Cholinesterase level
Plasma Cholinesterase
Comparison between RBC and plasma AchE
RBC AchE Plasma AchE
Better reflection of synaptic Easier to assay, decline
Advantages
inh faster
CNS gray matter, RBC, CNS white matter, plasma,
Site
Motor endplate 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
Acute exposure, response to
Use Acute exposure
treatment
Cirrhosis, malnutrition,
Pernicious,
hypersensitivity reaction,
hemoglobinopathies,
False depression drugs(succinylcholine,
antimalaria treatment,
codeine, morphine), genetic
oxalate blood tube
deficiency
Management
. Basic life support
Airway
Breathing
Circulation
2. Early mangement
J Prevent absorption:
gastric lavage
activated charcoal
skin decontamination
J Enhance Elimination
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)
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
Parathion
Pre-hospital management
Hot zone
¾ 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
¾ ABC Reminder
¾ Victim removal
Pre-hospital management
Decontamination zone
¾ Rescuer Protection: lower level of protection than that
worn in Hot Zone
¾ ABC Reminders
¾ 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
¾ Wash repeatedly with copious amounts of soap and water
¾ Rescuers wear rubber gloves as vinyl groves
¾ Clean hair, fingernails and skin folds
¾ Irrigate exposed or irritated eyes with plain water or
saline for 15 min
¾ Activated charcoal
¾ Not induce emesis
¾ Transfer to support zone
Pre-hospital management
Support zone
¾ Support zone team wear disposable aprons or
gowns and rubber gloves for protection
¾ ABC reminder
¾ Additional decontamination
¾ Advance treatment
¾ Antidotes
¾ Transport to medical facility
Emergency Department Management
¾ 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
¾ Critical Care area
- ABC reminder
- GI decontamination – gastric lavage, activated
charcoal
- Antidotes
- Laboratory test: RBC cholinesterase activity
Emergency Department Management
¾ 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)
G After 2- 4 wks after acute poisoning
G 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 Management
Hot zone
¾ 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
Prehospital Management
¾ ABC reminders
¾ There are 4 triage categories
¾ Antidote: difficult to achieve in Hot Zone
¾Victim removal: decontamination zone
Decontamination zone
¾ Rapid decontamination is critical to prevent further
absorption
¾ Rescuer protection: wear the same level of
protection as required in the Hot Zone
Triage for nerve agent casualties
Prehospital Management
¾ ABC reminder
¾ Antidotes
¾ 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
¾ Transfer to support zone
Support zone
¾ Victims must be decontamination properly
before entering the Support Zone
Prehospital Management
¾ ABC reminder
¾ Antidotes
¾ Additional decontamintion
¾ Transport to medical facility
Emergency Department Management
¾ 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
Emergency Department Management
¾ 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
- 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
¾ 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
¾ Report
Organochlorine poisoning
Organochlorine
DDT Benzene HCCyclodienes Toxaphene
Lindane** Aldrin ***
Endrin ***
Chlordane
**
Chlordeco
ne **
Inhalation Ingestion Dermal
Clinical Manifestation
Acute toxicity
Seizure threshold CNS stimulant
Respiratory failure
1-2 hr. postingestion
Ca +- ATPase neuronal
membrane
Increase Na+ Channel
opening time
tremor paresthesia myoclonus ocular movement weakness
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
Management
Basic life support
Early management
Prevent absorption: gastric lavage
activated Charcoal
skin decontamination
Support treatment: seizure
Chlordane
Pre-hospital management
Hot zone
¾ 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
¾ ABC Reminder
¾ Victim removal
Pre-hospital management
Decontamination zone
¾ Rescuer Protection: lower level of protection than that
worn in Hot Zone
¾ ABC Reminders
¾ Basic Decontamination:
- Quickly remove and double- bag contaminated
clothing and personal belonging
Pre-hospital management
¾ Flush with water 20 min then wash with soap twice
¾ Do not scrub
¾Irrigate exposed or irritated eyes with water or saline for
20 min
¾ Activated charcoal
¾ Not induce emesis
¾ Transfer to support zone
Pre-hospital management
Support zone
¾ABC reminder
¾ Additional decontamination
¾ Advance treatment
¾ Cardiac life support
¾ Transport to medical facility
Emergency Department Management
¾ 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
¾ Critical Care area
- ABC reminder
- GI decontamination – gastric lavage, activated
charcoal
- No antidotes
- Laboratory
Emergency Department Management
¾ Disposition and Follow- up
- history of serious exposure : admit
- Delay effect : pulmonary edema (Vapor)
- Discharge: asymptomatic
Paraquat
Herbicides
Diquat
2,4dichlorophenoxyacetic acid
Color : Blue-green
emetic agent
GSH GSSG
. .
O2 O2 OH
Paraquat Lung Lipid
peroxidation
Type I and II pneumocyte cell death & alveolitis
Lung fibrosis
GSH GSSG
. E .
O2 O2 2+
OH
Low FiO2 Fe F
C D
Paraquat Lung Lipid
A B peroxidation
Fuller’s earth, GI
Paraquat Ab
decontamination, HD
Type I and II pneumocyte
G cell death & alveolitis
H Lung fibrosis
การดูแลผูปวยที่ไดรับพิษจาก
paraquat
1. Basic life support
2. Prevent absorption
2.1 Gastric lavage
O2
2.2 Fuller’s earth
2.3 MOM 30 ml q 6 hrs
2.4 Skin decontamination
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
