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Pesticide Dr. Suda Vannaprasaht Department of Pharmacology Faculty of Medicine Khon 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 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 U M B E L S = Defecation = Urination = Miosis = Bradycardia = Emesis = Lacrimation = 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 Advantages Better reflection of synaptic inh Easier to assay, decline faster Site CNS gray matter, RBC, Motor endplate CNS 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 Use Acute exposure, response to treatment Acute exposure False depression Pernicious, hemoglobinopathies, antimalaria treatment, oxalate blood tube Cirrhosis, malnutrition, hypersensitivity reaction, drugs(succinylcholine, codeine, morphine), genetic deficiency Management 1. Basic life support Airway Breathing Circulation 2. Early mangement Prevent absorption: gastric lavage activated charcoal skin decontamination 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 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 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 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, selfcontained breathing apparatus - Skin protection: chemical-protective clothing and butyl rubber gloves 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 Triage for nerve agent casualties 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 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 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 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 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 HC Cyclodienes Lindane** Aldrin Endrin Chlordane Chlordecone Toxaphene *** *** ** 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 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 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 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 Paraquat Herbicides Diquat 2,4dichlorophenoxyacetic acid Color : Blue-green emetic agent . O2 Paraquat GSH GSSG O2 Lung Type I and II pneumocyte cell death & alveolitis Lung fibrosis . OH Lipid peroxidation . O2 Low FiO2 GSH O2 C D Lung B Paraquat A Fuller’s earth, GI decontamination, HD Paraquat Ab G Type I and II pneumocyte cell death & alveolitis H Lung fibrosis E GSSG . Fe 2+ F OH Lipid peroxidation การดูแลผู้ป่วยทีไ่ ด้ รับพิษจาก paraquat 1. Basic life support 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 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 “ ขอบคุณค่ ะ ”