Pesticides brc12 barry
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Pesticides brc12 barry

ACMT Board Review CourseJ. Dave BarryNaval Medical Center PortsmouthPortsmouth, VA

Disclosure Views expressed are solely those of the speaker and in noway reflect the official policy, position or doctrine of the USARMY, US NAVY, DOD or the US Government. The contents of this presentation are not endorsed in anyway by the US ARMY, US NAVY, DOD, or the USGovernment.

Pesticides Insecticides Fungicides Rodenticides Fumigants Herbicides Others

Insecticides Cholinesterase Inhibitors Organophosphates Carbamates Organochlorines Pyrethrins/Pyrethroids Newer Insecticides

InsecticidesCholinesterase Inhibitors Carbamates Ordeal (Calabar) BeanR-O(or S)OC NCarbamatesR 1R 2 Organophosphates SynthesizedR2OP(or S)R1XOrganophosphates

InsecticidesCholinesterase InhibitorsGoldfrank’s Toxicologic Emergencies – 8 th Ed (2006)

sympatheticAutonomic Nervous SystemparasympatheticMCNMneNTneNLSNMN

SympatheticParasympathetic (cholinergic)agitsecMCNMSzmiorrneNTsechrvasoconstrneNLsechrSNMmotsecNFasicparalymict

InsecticidesOrganophosphatesDelayed Syndromes Intermediate Syndrome Weakness 1-4d after exposure peripheral NMJ dysfunction ineffective AChE reactivation OPIDN Neuropathy target esterase (NTE) Lysophospholipase (lysoPLA) TOCP (tri-ortho cresyl phosphate) Jamaican ginger paralysis (1930’s) Cooking oils (1950’s)

RBC Cholinesterase Better reflection ofsynaptic inhibition Regenerates moreslowly than neuronalAchE Wide variationsInsecticidesOrganophosphatesin RBC disordersDiagnosis Butyrylcholinesterase(pseudocholinesterase) Falls first Recovers rapidly (few days) Wide daily variationin other disorders Liver dysfunction Malnutrition Drugs Pregnancy Genetic deficiency

InsecticidesCholinesterase Inhibitor Decontamination Protect Providers Glove BagTreatment Skin Triple wash – soap/water Shave scalp? GI Gastric? AC?

InsecticidesCholinesterase Inhibitor DecontaminationTreatment Antimuscarinic Agents Atropine Infusion 0.02 – 0.08 mg/kg/hr Bolus 2mg q 2-15 min / double dose Glycopyrrolate Scopolamine

InsecticidesCholinesterase InhibitorTreatment Decontamination Antimuscarinic Agents Benzodiazepine Diazepam

InsecticidesCholinesterase InhibitorTreatment Decontamination Antimuscarinic Agents Benzodiazepine(Organophosphates) Oximes Pralidoxime Obidoxime, HI-6 ?carbaryl?Bolus: 600mg q ?4hrInfusion: 1-2g load f/b500mg/hr

Aging & OximesInsecticidesOrganophosphatesR“Aging”Goldfrank’s Toxicologic Emergencies 8 th Ed.

InsecticidesOrganochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Hexachlorocyclohexane (lindane) Mirex and chlordecone

InsecticidesOrganochlorines Large family of neuroexcitatory toxins DDT and analogues Most banned fromindustrialized countries Na Ch Blockade Neuroexcitation

InsecticidesOrganochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Most banned fromindustrialized countries GABA Antagonists neuroexcitationGoldfrank’s ToxicologicEmergencies 8 th Ed.

InsecticidesOrganochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Hexachlorocyclohexane (lindane) Scabicide GABA Antagonist Seizures, neuroexcitationGoldfrank’s ToxicologicEmergencies 8 th Ed.

InsecticidesOrganochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Hexachlorocyclohexane (lindane) Mirex and chlordecone Hopewell Epidemic (1974) “Kepone Shakes”Goldfrank’s ToxicologicEmergencies 8 th Ed.

InsecticidesPyrethrins/Pyrethroids Pyrethrins Naturally occuring NaCh openers Rapidly decompose Pyrethroids Synthetic derivatives More persistent, potent Piperonyl butoxide P450 inhibitor

InsecticidesPyrethrins/Pyrethroids Toxicity Pyrethrins Allergic Pyrethroids Type 1 Non-CN “T” Syndrome Tremor Low tox in humans Type II -CN More potent “CS” Syndrome Choreoathetosis, salivation GI (saliv, n/v/d), pulmonaryneuroexcitation

InsecticidesPyrethrins/Pyrethroids Treatment Supportive Decontamination Skin GI - AC

InsecticidesOthers Boric Acid Ant/cockroach killer Mechanism unclear Symptoms GI (blue-green emesis/diarrhea) Kidney CNS/Neuro Derm (boiled lobster rash)

InsecticidesOthers Amitraz 2-agonism Fipronil GABA antagonist Insect:Human 1000:1 Imidacloprid Nicotinic Treatment supportive Avermectins (abamectin, ivermectin) Fermentation of Streptomyces avermitilis


RodenticidesCompound 1080/1081 Sodium Monofluoroacetate (SMFA) Compound 1080 Flouroacetamide Compound 1081 Inhibit aconitase in Krebs cycle “lethal synthesis”

Compound 1080/1081

RodenticidesCompound 1080/1081 Symptoms apprehension dysrhythmias, seizures,coma, ↓ Ca Not flouride toxicity Treatment Unknown Ethanol, Glycerolmonoacetate,

RodenticidesPNU (Vacor) n-3-pyridylmethyl-N-p-nitrophenyl urea Interferes with nicotinamideactivity in pancreas, brain, liver Rapid development of Diabetes mellitus (DKA) Orthostatic hypotension CNS toxicity GI perforation

RodenticidesPNU (Vacor) Treatment Aggressive Decontamination Nicotinamide Niacin

RodenticidesPhosphine Rodenticide (Zinc Phosphide) Fumigant (Aluminum Phosphide) Phosphine gas Cellular poison Inhibits cytochrome oxidase and ETC Rotten fish / garlic-like odor

RodenticidesPhosphene Symptoms Low level exposure Pulmonary edema (delayed) High level exposure Multisystem failure N/V, coma, seizures, hypertension,pulmonary edema

RodenticidesPhosphene Treatment Inhalation – supportive Ingestion Intubation lavage/suction diluted HCO3 solution, milk Supportive NAC, Mg

RodenticidesStrychnine Strychnos nux vomica Glycine inhibition Involuntary generalizedmuscular contractions Opisthotonos, trismus,risus sardonicus Treatment Benzodiazepines NM Blockade

RodenticidesATNU α-naphthyl-thiourea Acute pulmonary edema Mechanism unknown

History ‘superwarfarins’ Longer T1/2 100X more potent Same mechanism

WarfarinsVit KQuinoneExogenousVitamin K(phytonadione)Vit Ki (inactive)Vit K 2,3 epoxideVit Ka (active)hydroquinoneFFPFactors II,VII,IX,XFactors Iia,VIIa,Ixa,Xa (active)

Diagnosis & Treatment Child/unintentional none Suicidal/other Labs Vit K 1 (phytonadione) IV, PO, IM FFP

Bromethalin Uncouples oxidative phosphorylation AMS, myoclonus, seizures, coma Norbormide (dicarboximide) Norway rat selective smooth muscle constriction Death from profound vasoconstriction Other rats, rodents, humans don’t have the samereceptor or transporter

Herbicides Bipyridyl herbicides Paraquat Diquat Chlorphenoxy herbicides 2,4-D, 2,4,5-T and Agent Orange Glyphosate Anilide derivatives

Paraquat/Diquat Redox cycling 1 – depletion ofNADPH 2 – superoxideformation 3 – lipid peroxidationcascade 4 – glutathione &NADPH depletionGoldfrank’s Toxicologic Emergencies 8 th Ed.

Paraquat Active transportinto Type I & IIalveolar epithelialcells Surfactantdepletion,destruction ofalveoliGoldfrank’s Toxicologic Emergencies 8 th Ed.

Symptoms Dependant on amount ingested May be delayed, especially with dilute products Caustic (Skin, GI Mucosa) Renal Toxicity/Failure ARDS Paraquat – pulmonary fibrosis CNS (somnolence, coma, sz, etc) Diquat – predilection for pontine hemorrhage?

Treatment Skin Decon Lavage (N/V usually occur though) AC, Fuller’s earth, bentonite, garden clay Hemodialysis, hemoperfusion,hemofiltration ?No O 2 until PaO 2 < 50mm Hg

chemical analogs of auxins (a plant growth hormone) Uncontrolled and lethal growth

Corrosive, cell membrane damage form Acetyl Co-A analogues, uncouple oxid phos? Symptoms Treatment GI supportive N/V, abdominal pain, diarrhea CV hypotension, nonspecific ECG abnormalities CNS coma, hypertonia, hyperreflexia,Ukrainian oppositionpresidential candidateViktor Yushchenko

Plant mechanism – amino acid analogue Human mechanism – unclear, difficult to separate the toxicity of glyphosate fromsurfactants and other additives Symptoms GI/caustic Pulmonary (?aspiration) CV, renal, CNS toxicity Treatment supportive

amidepropanilacetochlor Symptoms methemoglobinemia Treatment Methyleneblue

Fungicides Metallic/organo-metallic Ba, Cu, Cd, Sb, Hg Substituted Aromatics Chlorothalonil, pentachlorophenol,hexachlorobenzene Thiabendazoles Benomyl, terrazole, thiabendazole


Fumigants Phosphene – see rodenticides Methyl bromide Sulfuryl flouride

FumigantsMethyl Bromide Heavier than air Chloropicrin additive Phased out (oxone-depleting agent) Skin irritation, blistering Pulmonary dyspnea, NCPE CNS visual disturbances, tremor, sz, coma Treatment supportive

FumigantsSulfuryl Fluoride (Vikane) Heavier than air Chloropicrin Suspected flouride poisoning mechanism Mucus membranes (skin, GI, resp) irritation, blistering CNS CV paresthesias, tremor, sz, coma Shock, cardiac dysrhythmias Treatment Supportive monitor Ca

PesticidesOthers Moth balls DEET Molluscicides

OthersMoth BallsH2OSaltwaterXR Sx TxCamphor float float luc CNS/Sz supportNapthalene sink floatfaintopmetHbHemolysismethblueParadichloro-benzenesink sink opN/V, HA,CNSsupport

OthersDEET N,N-diethyl-3-methylbenzamide Wide safety margin Primarily CNS toxicity Only after high doses

OthersMolluscicides quaternary ammonium compounds carbamates metals Metaldehyde acetaldehyde? GI – N/V/D, abdominal pain CNS – seizures, coma, hyperthermia

Pesticides Insecticides Fungicides Rodenticides Fumigants Herbicides Others

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