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Pesticide Department of Pharmacology Faculty of Medicine

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Presentation on theme: "Pesticide Department of Pharmacology Faculty of Medicine"— Presentation transcript:

1 Pesticide Department of Pharmacology Faculty of Medicine
Dr. Suda Vannaprasaht Department of Pharmacology Faculty of Medicine Khon Kaen University, Thailand

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

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

12 JAMA 2003;290:661

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

14 Intensive Care Med 1997;23:1006

15 True Cholinesterase (RBC) Plasma Cholinesterase
Investigation True Cholinesterase (RBC) Cholinesterase level Plasma Cholinesterase

16 Comparison between RBC and plasma AchE

17 Management 1. Basic life support Airway Breathing Circulation

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

19 1. Atropine antimuscarinic
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

20 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

21 Pre-hospital management
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

22 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

23 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

24 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

25 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

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

27 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

28 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

29 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

30 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

31 Prehospital Management
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

32 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

33 Triage for nerve agent casualties

34 Prehospital Management
ABC reminder Antidotes Basic decontamination: Liquid - eyes decontamination within minutes of exposure - flush eyes with water for 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

35 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

36 Prehospital Management
ABC reminder Antidotes Additional decontamintion Transport to medical facility

37 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

38 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

39 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

40 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

41 Emergency Department Management
- Follow up - severe exposure: CNS sequelae Report

42

43 Organochlorine poisoning

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

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

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

47 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

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

49 Pre-hospital management
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

50 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

51 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

52 Pre-hospital management
Support zone ABC reminder Additional decontamination Advance treatment Cardiac life support Transport to medical facility

53 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

54 Emergency Department Management
Critical Care area - ABC reminder - GI decontamination – gastric lavage, activated charcoal - No antidotes - Laboratory

55 Emergency Department Management
Disposition and Follow- up - history of serious exposure : admit - Delay effect : pulmonary edema (Vapor) - Discharge: asymptomatic

56 Paraquat Toxicity

57 Paraquat Herbicides Diquat
2,4dichlorophenoxyacetic acid Color : Blue-green emetic agent

58 . . O2 O2 OH Lipid peroxidation Lung Lung fibrosis GSH GSSG Paraquat
Type I and II pneumocyte cell death & alveolitis Lung fibrosis

59 Fuller’s earth, GI decontamination, HD
GSH GSSG . . E O2 O2 OH Fe 2+ Low FiO2 F C D Paraquat Lipid peroxidation Lung A B Fuller’s earth, GI decontamination, HD Paraquat Ab Type I and II pneumocyte cell death & alveolitis G H Lung fibrosis

60 การดูแลผู้ป่วยที่ได้รับพิษจาก paraquat
O2 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

61 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

62 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

63 “ ขอบคุณค่ะ ”


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