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Pesticide

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  1. Pesticide Dr. Suda Vannaprasaht Department of Pharmacology Faculty of Medicine Khon Kaen University, Thailand e-mail: sudvan@kku.ac.th

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

  3. Organophosphate Insecticide • Parathion • Malathion • Fenthion • Dimethoate • Monocrotophos • Metamidophos

  4. Carbamate Insecticide • Carbaryl • Carbofuran • Propanocarb • Thiodicarb

  5. 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

  6. Organophosphate Chemical warfare • Nerve agents • Tabun • Sarin • Soman • VX

  7. Sarin Gas Attack in Japan • June 1994, Matsumoto (614) • March 1995, Tokyo subway (5510)

  8. 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

  9. Mechanism of Intoxication

  10. Muscarinic Receptor • = Defecation • = Urination • = Miosis • = Bradycardia • = Emesis • = Lacrimation • = Secretion D U M B E L S

  11. JAMA 2003;290:661

  12. Relationship between pupil size and AChE activity in patient exposed to sarin vapor Intensive Care Med 1997;23:1006

  13. Intensive Care Med 1997;23:1006

  14. Investigation True Cholinesterase (RBC) Cholinesterase level Plasma Cholinesterase

  15. Comparison between RBC and plasma AchE

  16. Management 1. Basic life support • Airway • Breathing • Circulation

  17. 2. Early mangement • Prevent absorption: gastric lavage activated charcoal skin decontamination • Enhance Elimination

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. Emergency Department Management • Critical Care area - ABC reminder - GI decontamination – gastric lavage, activated charcoal - Antidotes - Laboratory test: RBC cholinesterase activity

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. Triage for nerve agent casualties

  33. 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

  34. 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

  35. Prehospital Management • ABC reminder • Antidotes • Additional decontamintion • Transport to medical facility

  36. 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

  37. 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

  38. 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

  39. 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

  40. Emergency Department Management • - Follow up • - severe exposure: CNS sequelae • Report

  41. Organochlorine poisoning

  42. Organochlorine DDT Benzene HC Cyclodienes Toxaphene Lindane** Aldrin*** Endrin*** Chlordane** Chlordecone** Inhalation Ingestion Dermal

  43. Clinical Manifestation • Acute toxicity • Seizure threshold & CNS stimulant • Respiratory failure • 1-2 hr. postingestion

  44. Ca2+- ATPase neuronal membrane • Increase Na+ Channel opening time tremor paresthesia myoclonus ocular movement weakness

  45. 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

  46. Management • Basic life support • Early management • Prevent absorption: gastric lavage activated Charcoal skin decontamination • Support treatment: seizure

  47. 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

  48. 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