Death by pesticides Flashcards
Insecticides
Cholinesterase Inhibitors; OP and Carbamates
Organochlorines; Chlorodecone, Lindane, DDT
Pyrethrins/Pyrethroids; Permethrin, Deltamethrin
Acetylcholine is located where?
Sympathetic and Parasympathetic ganglia Skeletal NMJ Post ganglionic sympathetic nerves Sympathetic sweat glands CNS nerve endings
What is a muscarinic receptor?
G protein linked
What is a nicotinic receptor?
Ligand mediated ion channel
What is the Cholinergic Toxidrome acronym?
DUMBBELS; Muscarinic Diarrhea Urination Miosis Bronchorrea Bradycardia Emesis Lacrimation Salivation
What are organic phosphorous compounds?
Increase ACh concentration in synapse muscarinic and nicotinic
Cholinergic toxidrome
X is the leaving group
Organic phosphorous compounds oxons vs. thions
oxons = direct action on AChE thions = prodrugs; must be converted to active compound by p450 enzymes
What is the mechanism of action for oxons and thions?
Ex of oxons: 2 PAM or praladoxime
binds to hydroxyl group of AChE active site
stable but reversible bond forms
speeds up rate of reactivation of AChE
aging occurs when oximes can’t reactivate AChE (bond becomes permanent)
What do OP’s and Carbamates inhibit?
carboxylic ester hydrolases in the body
Acute toxicity of cholinesterase inhibition presentation?
Awake and alert
anxiety, restlessness, myosis blurred vision, respiratory depression, tremor
altered mental status - confusion - coma
DUMBBELS
How to diagnose cholinesterase inhibition?
measure cholinesterase activity for organophosphate exposure by Red blood cell AChE or ButyrylChE
miosis, muscarinic signs, and SOB
What are carbamates?
Aging does not occur therefore, no permanent bond between carbamate and AChE
What is carbamate acute toxicity?
like OP toxicity
coma and respiratory failure
Shorter duration than OPs b/c reversible
What are delayed syndromes of AChE inhibitors?
NMJ dysfunction aka intermediate syndrome
delayed muscle weakness w/o cholinergic toxidrome
24-96 hours after exposure
muscle weakness leads to respiratory failure
1st sign is muscle weakness
OP cmpd induced delayed neuropathy
Drinking OH w/TOCP ginger jake developed delayed neuropathy
Acute/ Chronic OP exposure causes?
behavioral toxicity;
confusion, psychosis, anxiety, depression, and fatigue
EEG changes for weeks
What causes chronic toxicity of OPs?
occupational exposure
BuChE activity is the sensitive measure of exposure
RBC cholinesterase is like Neuronal cholinesterase
Neuronal Target Esterase Inhibition to look for delayed neuropathy
What is the primary cause of death for AChE inhibition?
What is the general management?
respiratory failure due to bronchorrea
adequate airway/drying up secretions with atropine
benzodiazepines for seizures
Pharmacotherapy for AChE inhibition?
Atropine sulfate for carbamates = competitive anatagonist at central and peripheral muscarinic receptors/crosses BBB
Pralidoxime (2-PAM) for OP’s = targets nicotinic receptors to reverse muscle weakness/reactivates cholinesterase/prevents aging of AChE
Antimuscarinic Therapy
does not reverse nicotinic effects
ex: atropine
What are oximes?
enhances phosphorylated AChE regeneration via hydrolysis
prevents aging and addresses nicotinic and muscarinic effects
Pralidoxime mechanism?
binds on anionic site of AChE by pulling off organophosphate there
What are Benzodiazapines?
given to prevent seizures from cholinergic syndrome
Ex: diazepam
can use for intubation induction
anticholinergic
What is decontamination?
remove all clothing
triple wash skin -water, soap, water and rinse with water
wear. neoprene/nitrile gloves
consider lavage for large acute ingestions
AC but protect airway to prevent vomiting
What are organochlorine compounds?
family of neuroexcitatory toxins; all neurotoxins
eggshell thinning so changed agriculture
Ex: DDT
Can bioaccumulate and potentially cause harm
Illegal in US
DDT eliminated malaria
For organochlorine cmpd toxicity what do you give?
automatically give atropine and 2 PAM & it’s safe in large doses
Hopewell Pesticide Spill?
made Kepone(chlordecone) dumped in James River neurotoxicity Kepone shakes Hepatic injury Testicular dysfunction
What are neurotoxins in Organic Chlorines?
interfere with repolarization and depolarization of neuronal membranes
results in hyperexcitability
Lindane is GABA antagonist
Acute Toxicity of Organic Chlorines?
CNS stimulation - seizure - respiratory failure - death
Chronic Toxicity of Organic Chlorines?
ex: hopewell epidemic
body tremor
AMS, Ataxia, weakness
DDT linked to breast cancer
Treatment for organic chlorines?
supportive care
lavage for recent ingestion
AC cannot bind so not likely
benzodiazepines for seizures and for greater strength can use barbiturates or propofol
Pyrethrins
extracts from Chysanthemum flower
lipohilic
sodium channel opening causing insect paralysis
Pyrethroids
synthetic derivative
limited human toxicity and no bioaccumulation so more common
Pyrethroid types?
Type I - simple ester bond, no cyano group
ex: permethrin
Type II - have a cyano group and more toxic
pyrethrins and pyrethroids mechanism?
prolong activation of voltage gated Na channel
binds to open channel and keeps open
paralyzes insect
Clinical effects of pyrethrin and pyrethroids?
most are allergic rxns
pyrethroid type 1 clinical effects?
type 1 - tremors and twitching
human tox rare
selective to insects
pyrethroid type 2 clinical effects?
more potent/toxic
acute lung injury
CS syndrome= choreoathetosis and salivation
paresthesias, salivation, nausea, vomitng, AMS, seizures
pyrethrins and pyrethroids treatment?
supportive care skin decontamination by washing AC for ingestion BZD for seizures Vitamin E oil for cutaneous paresthesias
herbicides?
regulates plant growth
mainly weed killer
most widely sold pesticide in world
Bipyridyl compounds
paraquat and diquat
nonselective contact herbicides
paraquat = most toxic pesticide (100% death for intentional poisoning)
Diquat still fatal but less toxic
Paraquat and Diquat mechanism?
both highly irritating and corrosive - direct injury
generate Reactive Oxygen Species - damages lipid membranes
Redox Cycling =
clinical manifestation of paraquat and diquat?
GI symptoms nausea and vomiting oral and throat pain b/c corrosive necrosis of mucous membranes respiratory symptoms mainly w/ paraquat AKI MSOF and death
paraquat and diquat treatment?
supportive care resuscitate giving O2 makes injury worse b/c redox cycling decontamination fullers earth or AC
chlorphenoxy herbicides?
dioxin
agent orange is nerve agent
carcinogenic
chloracne
agent orange
chlorphenoxy herbicide defoliant
has dioxin
plant growth hormone analogue
cancer and birth defects
what are other herbicides?
glyphosate anilide derivatives: propanil, acetochlor cause methemoglobinemia treat with methylene blue
what is glyphosate?
kills weed which compete with crops
used around world b/c no sever effect like paraquat
doesn’t inhibit ACh
glyphosate Toxicity?
inhibits 5-e-3-p synthase interferes with amino acids human toxicity mech not understood technically an OP but does not inhibit ACh surfactant coformulation = more toxic
clinical effects of glyphosate?
stomach pain, nausea, vomiting, diarrhea
MSOF
treatment: supportive care
fumigants
nonspecific pesticides so can kill rodents, nematodes, insects, weeds, fungi
most common exposure = inhalation
heavier than air so sinks down does not dissipate
list of fumigants?
phosphides/phosphine
methyl bromide
sulfuryl fluoride (vikane) - sucks up calcium in body
phosphides and phosphine fumigant?
metal phosphides
cheap and effective
seed viability unaffected
mixed with grain/food storage
mixed with moisture releases phosphine gas(PH3)
smells like mown hay and no immediate effect
epidemiology of phosphides and phosphine?
increased incidence of poisoning
high rate of mortality
suicide attempts
physical properties of phosphides and phosphine
aluminum phosphide: greenish gray tablets, garlic odor
zinc phosphide: dark gray powder, rotten fish odor
gaseous PH3: colorless, decaying fish or garlic odor
heavier than air
phosphides and phosphine mechanism of action?
non competive inhibition of cytochrome c oxidase (mitochondria electron transport chain)
blocks oxidative phosphorylation
phosphide and phosphine clinical effects
tachycardia, SOB, tachypnea,
smell of garlic or rotting fish on breath
phosphides and phosphine treatment
remove from source give O2 use PPE remove clothes decontaminate with water AC in 1 hour supportive care
methyl bromide
fumigation poisoning colorless odorless gas heavier than air exposure by inhalation dermal and oral apsorption rapid distribution to tissue
methyl bromide fumigant mechanism?
cytotoxic - directly damages cells and dna
alkylating
inhibits microsomal metabolism and protein synthesis in animal models
methy bromide fumigant clinical effects
ARDS leads to respiratory failure and death
skin and mucous membrane irritant
CNS effects
methyl bromide fumigant treatment
ppe for provider protection remove from source remove clothing decontaminate with water or saline supportive care
fungicides
dithiocarbamates
metabolized to carbon disulfide
causes neuropathy
disulfiram like rxns (asian flush from impairment of OH metabolism)
molluscicides
kills gastropod pests like snails and slugs includes: carbamates metal metaldehyde
Rodenticides
BRATS PANIC
anticoagulant rodenticides most common in US
clinical effects: bleeding, bruising
Testing: elevation of coagulation parameters
