Organochlorines and Organophosphates Flashcards
What is a pesticide?
Chemical (natural or synthetic) and other products used to kill, repel, or control pests
What is the major federal agency regulating pesticides?
U.S environmental protection agency (EPA)
The federal insecticide, fungicide, and rodenticide act governs??
Sale and use of pesticide products within the US
The federal food, drug, and cosmetic act governs ???
The limit of pesticide residues on food or feeds
Who approves uses and conditions of use (safe methods, personal protection, ventilation, storage, and disposal ) of pesticides?
EPA
EPA determines a “safe” level of pesticide residue called a ____________
Tolerance
What are sources of organochlorines?
Natural through biological, physical, and chemical processes
-> bacteria, fungi, plants, marine organisms, insects ect
Synthetic -> chlorination process modifying hydrocarbon
Are organochlorines hydrophilic or lipophilic?
Lipophilic
What makes organochorines so persistent in the environment?
Chlorination of organic compounds reduces reactivity,
Increased size, decreased volatility, increased boiling point
==> stability = environmental persistence
What are the two main groups of organochlorine pesticides??
Dichlorodiphenyltrichloroethane (DDT)
Chlorinated alicyclics
What environmental impacts does DDT have?
Bioaccumulation-> long half life and accumulation infatty tissue -> toxic levels and death
Biomagnification -> organisms higher in food chain eat lower food chain with concentrations of DDT that is magnified
What type activity does DTT have that can lean to egg-shell thinning?
Estrogen like activity
-impairs the shell gland’s ability to excrete calcium carbon to harden the egg shell
______________ was developed to replace DDT, caused acute toxicty, bioaccumulation, and endocrine disruption activity
Methoxychlor
_______________ has been banned by EPA for agricultural use but is still approved by FDA for pharmaceutical treatment of lice and scabies
Lindane
Exposure to organochlorines usually results from??
Not following label directions
Miscalculation of concentrations for sprays to dipping
Unsecured/unlabeled packages/containers
Lack of PPE
How are organochlorines pesticides absorbed?
Dermal -> damaged skin facilitates absorption
Lindane and Endosulfan -well absorbed
DDT, Mirex, dicofol, toxophene -less
T/F: when you suspect organochlorine toxicity, you should give fats or organic solvents to decrease absorption across the GI wall
False
Organochlorines are lipophilic -> fats and organic solvents will increase their absorption
Where are organochlorines distributed and stored in the body?
Stored in fat/lipid fraction of blood and other tissues
T/F: organochlorines are biologically inactive when partitioned and stored in adipose tissue ?
True
What can cause mobilization of organochlorines resulting in toxic levels in the circulation?
Disease, aging, fasting, lactation
What is the MOA of DDT type pesticides ?
Prevents neuronal repolarization by maintaining Na channels open —> continued neurotransmitter release and hyperexcitabilty of the nervous system
What is the MOA of organochlorine pesticides?
Binds but does not activate GABA receptors (antagonist)
GABA is inhibitory in CNS -> reduces neuronal excitability/enhance repolariztion
—> inhibit repolariztion
How are organochlorines metabolized?
Liver enzymes —> most dechlorinated, conjugated, and excreted
Metabolites of organochlorines which means they can be re-absorbed through what route?
Enterohaptic recycling
How are organochlorines excreted?
Milk
Feces
Urine
What is the main clinical sign on organochlorine toxicity?
CNS hyper stimulation
What are the clinical signs caused by organochlorine pesticides ?
Salivation, vomiting, apprehension, weakness, incoordination, and disorientation
Tremors, muscle fasciculation, spastic gait, hyperthermia, abnormal posturing, chewing
Tonic-clonic seizure, opisthotonos, coma, death
How can you diagnose an organochlorine toxicity?
No specific lesions
Chemical analysis -liver brain or blood levels high enough
History of exposure, clinical signs, lack of specific lesions, chemical analysis
PIG
Salivation, vomiting, apprehension, weakness, incoordination, and disorientation
Tremors, muscle fasciculation, spastic gait, hyperthermia, abnormal posturing, chewing
Tonic-clonic seizure, opisthotonos, coma, death
DDx??
Organochlorine toxicity
Dehydration/Na imbalance
pseudorabies
DOG or CAT
Salivation, vomiting, apprehension, weakness, incoordination, and disorientation
Tremors, muscle fasciculation, spastic gait, hyperthermia, abnormal posturing, chewing
Tonic-clonic seizure, opisthotonos, coma, death
DDX?
Organochlorine Strychnine Fluoroacetate Lead OP Metaldehyde Rabies
Cattle
Salivation, vomiting, apprehension, weakness, incoordination, and disorientation
Tremors, muscle fasciculation, spastic gait, hyperthermia, abnormal posturing, chewing
Tonic-clonic seizure, opisthotonos, coma, death
DDX?
Organochlorine OP Lead Urea Polioencephalomalacia Infectious thromboembolic meningoencephalitis Ketosis Nervous forms of coccidiosis
What is the treatment of organochlorine toxicity?
No specific antidote
Decontaminate
- wash soap/water if dermal exposure
- Induce emesis
- mineral oil or activated charcoal
- IV lipid or fat emulsion (last resort)
Symptomatic
- diazepam or barbiturates to control seizures
- oxygen, ventilation, fluids
What is the MOA of organophosphates?
Irreversible inactivate acetylcholinesterase —> persistent ACh activity
How are animals usually exposed to organophosphates?
Contaminated feed or drinking water
Sheep dip or other applications, flea treatment, or medications
Overdose
Intentional poisoning
T/F: thiophosphate OPs are more lipid soluble than phosphate OPs
True
Are organophosphates easily degradable??
Yes
Generally persist for 2-4wks
Residues on fruit, veg, and crops may last longer
What is storage activation?
When stored a chemical becomes more toxic
Eg Parathion, malathion, diazinon, coumaphos
How are organophosphates absorbed?
Skin and mucous membranes, GIT, and inhalation (lipophilic)
What are the usual exposures for organophosphates?
Dip or spray -dermal absorption
Contaminated feed or water - oral
Aerial/indoor spray- inhaled
Where are organophosphates metabolized?
Liver- excretion/bioactivation
____________ occurs when liver enzymes metabolize thiophosaphate OPs
Lethal synthesis
Continued low dose exposure to organophosphates can have what affect on nervous system??
Adaption do decreased acetylcholinesterase (homeostatic response)
—> Enzyme induction or increased acetylcholinesterase production
—> receptor down regulation or decrease ACh receptor
T/F: phospahate OPs require hepatic bioactivation “lethal synthesis”
False
Phosphate OPs are biologically active
Thiophosphate OPs require lethal synthesis by de-sulfuration
T/F: thiophosphate OPs undergo enteroheptic recycling
True
Highly lipid soluble
Where are thiophosphate OPs stored?
Adipose tissue
Slow release from fat may lead to delayed and/or prolonged cholinesterase inhibiton
What is a major route of elimination of thiophosphate OPs?
Paroxonase (serum bound enzyme)
What are the three MOAs of organophosphates ?
Inhibit cholinesterase
Primary: muscarinic over stimulation —>PSNS
Secondary: nicotinic receptor over stimulation —> CNS and neuromuscular stimulation
Tertiary: nicotinic blockade —> neuromuscular blockade and CNS depression
Organophosphate toxicity leads to over stimulation of the muscarinic receptors by ACH, what are the symptoms caused by this?
DUMBELLS
Diarrhea Urination Miosis Bronchospasm Emesis Lacrimation Salivation
Organophosphates have a secondary effect of activation of nicotinic receptors, what signs may you see due to this?
Accumulation of ACh at neuromuscular junction —> paralysis (nicotinic block)
Sweating, hypertension, and tachycardia
Organophosphates can cross the BBB, what effects will it have int he CNS?
Increased sensory and behavioral disturbances
Incoordination
Depressed motor and respiratory function
What is usually the cause of death in animals with organophosphate toxicity?
Increased pulmonary sections with respiratory failure
What pathology can be associated with organophosphates?
Acute death, no specific lesions
Pulmonary edema Congestion Cyanosis Hemorrhage Edema Necrosis of skeletal muscle
How is organophosphate toxicity diagnosed?
Analysis or stomach/rumen contest/ hair/ skin
Plasma acetylcholinesterase activity level
<50% activity is suspicious
<25% activity is diagnostic
What test can be done in clinic if you suspect organophosphate toxicity?
Atropine response test
-has antimuscarinic effect —> ininbit the PSNS
Has no effect on the nicotinic induce paralysis
If atropine positive—> dry skin and mucous membranes, increased heart rate, dilate pupls (low likelyhood of OP poisoning)
If atropine neg-> see none of the above signs due to excessive ACh stimulation —> OP toxicity
What is the treatment for OP toxicity?
Decontamination
Supportive care
Atropine —> block muscarinic receptor interaction
Cholinesterase reactivators—> reverses OP binding to acetylcholinesterase (pralidoximine or 2-PAM)
Avoid phenothiazines, aminoglycosides, muscle relaxants, and drugs that depress respiration
What is the main concern with OP toxicity?
Respiratory failure (asphyxia and death) from excessive airway secretions
T/F: carbamates require hepatic bioactivation
False
—> this makes them more toxic than some OPs in very young patients
Where doe carbamates mostly have an effect?
Respiratory
-do not penetrate CNS
What is the MOA of carbamates?
Binds acetylcholinesterase but is REVERSIBLE
—> shorter duration and less important consequences than OPs
What are the clinical signs seen with carbmate poisoning?
Similar to OP toxicity
SLUD Salivation Lacrimation Urination Diarrhea
What tests can be used to diagnose carbamate toxicity
Cholinesterase levels
->because of reversible binding, can dissociate and give a false negative result
Response to atropine therapy
What is the treatment for carbamate toxicity
Decontamination
Supportive therapy
Atropine
Oxides/PAM-2 no as effective because of reversible binding (in some cases can increase binding)
With regards to toxicity, which option is false
A. Phosphate OPs require hepatic bioactivation
B. Thiophosphate OPs do not require hepatic bioactivation
C. Carbamate required hepatic bioactivation
D. All of the above
D
