Nicotine, Neonicotinids, And Naphthalene Flashcards
How is Naphthalene produced?
Combustion
- cigarette smoke
- car exhaust
- forest fire smoke
How do mothballs act as a pesticide?
Slow release of naphthalene gas vapor that kills and repels moths/insects
How do the old version of mothballs differ from the new version?
Old -naphthalene (highly toxic and flammable)
New- paradichlorobenzes (less toxic)
Are cats or dogs more sensitive to naphthalene?
Cats
But dogs are more likely to ingest
What is the lowest canine lethal dose of naphthalene?
400mg/kg
One mothball can be 2.7-4g —> single mothball can be highly toxic
Generally, what is the exposure route to naphthalene?
Absorbed through inhalation, orally and dermally
Vapor can cause eye irritation
Repeated exposures can cause skin rash/cataracts
How do oils afffect absorption of naphthalene?
Lipid soluble —> increase absorption
Acids _________and bases __________ stomach absorption of naphthalene
Delay; enhance
Where is naphthalene distributed after is is absorbed?
Bloodstream —> rapid distribution to adipose tissue
Found in high concentrations in adipose, kidney, liver, and lungs
Cross placental
Excreted in milk
How is naphthalene metabolized?
Hepatic enzyme
-> expoxide or quinones (cause cellular damage)
- > conjugated with glutathione to non-toxic metabolites
- > conjugation with sulfate, glucuronic acid, or mercapturic acid to be excreted in urine or bile
What is the MOA of naphthalene?
Oxidative metabolites in the circulation can cause hemolysis and methemoglobinemia
- hemolysis - rupture of RBC
- methemoglobinemia - decrease ability to bind oxygen —> tissue hypoxia
What are clinical signs associated with naphthalene ?
Dissolve slowly when digested in acid stomach but show up days when in basic intestines
Salivation Vomiting Mothball breath Pale or brown gums Methemoglobinemia, hemolytic anemia, or hemoglobinuria Weakness or lethargy Labored breathing Tremors and seizures Cataracts in neonates
How can you diagnose naphthalene toxicity?
Hematologic changes
- hemolysis and heinz bodies
- methemoglobinemia (chocolate brown blood)
- hemoglobinuria
What is the prognosis for naphthalene toxicity?
Good for those treated promptly and without pre-existing liver or kidney disease
What is the treatment for naphthalene toxicity?
Decontamination
- emesis and activate charcoal
- sodium bicarb —> reduced precipitation of hemoglobin in kidney
- IVfluids
Specific treatment for methemoglobinemia
- ascorbic acid
- methylene blue 1%
What role does ascorbic acid play in treatment of naphthalene ?
Reduce methemoglobin to hemoglobin (relatively slow conversion)
How does methylene blue help treat naphthalene toxicity?
Leucomethylene blue is a reducing agent at low dose to make methemoglobin —> hemoglobin
Do we use a high dose or low does of methylene blue in naphthalene toxicity?
Low (reducing quality)
At high doses methylene blue has oxidizing effect and can increase methemoglobin
What does nicotine come from?
Water soluble alkaloid from dried eaves of tobacco plant
How are animals exposed to nicotine?
Insecticides
- absorbed through the mucous membranes and respiratory tract (caustic)
- ingestion of contaminated feces
Ingestion of tobacco products (leaves, cigarettes, cigars)
Do acids delay or enhance grastric absorption of nicotine ?
Delay
How toxic is nicotine to dogs?
Highly toxic
oral LD50 of 9.2mg/kg
Cigarette has 9-30mg
Cigars 45-150mg
What are the toxicokinetics of nicotine?
Enters the body and is distributed rapidly through the bloodstream, including CNS
Half life about 2hrs in human
Where is nicotine metabolized and excreted?
Liver metabolize to cotinine and nicotine oxide
Metabolites excreted in urine
Does renal excretion increase/decrease in an acidic urine?
Increase
What is the MOA of nicotine toxicity?
Potent stimulant of PSNS
-cholinergic receptor agonist
At low dresses, mimics ACh and stimulates CNS, ganglia and neuromuscular junctions
At high dose, stimulation followed by blockage (nicotinic block)
What clinical signs are associated with nicotine toxicity?
Early
- ataxia, lethargy
- hypersalivation, vomiting
- bradycardia
- tremors/convulsions
Late
- CNS depression, tachycardia, vasodilation
- paralysis of respiratory muscles (resp failure)
How can you diagnose nicotine toxicity?
Observation
History of exposure and clinical signs
Antemortem- tox analysis of blood, vomitus, gastric contents, and urine
PM- liver analysis, kidney, other tissues
Early
- ataxia, lethargy
- hypersalivation, vomiting
- bradycardia
- tremors/convulsions
Late
- CNS depression, tachycardia, vasodilation
- paralysis of respiratory muscles (resp failure)
What is your DDx?
Strychnine Methylxanthines Tremorgenic mycotoxins Organophosphates Carbamates Depressants
How do you treat nicotine/neonicotinoid toxicity?
Decontamination
- emesis or gastric lavage
- auto decontamination-CRTZ stimulation and vomiting
- activated charcoal
- avoid antacids which promote absorption
Enhance excretion (diuretics) -iv fluids or lower urine pH
Atropine for parasympathetic effects (in late phase)
Diazepam to control seizure
What is the prognosis for nicotine toxicity?
If animal survives the first 4 hours, prognosis is good
Grave if large amounts have been ingested
What is one of the most widely used insecticide used in the world (about 25% of all insecticide use)
Neonicotinoids
-imidacloprid (the most widely used)
What is the source of neonicotinioids?
Synthetic insecticides that are similar to nicotine
Are neonicotinoids lipid/water soluble??
Water soluble
How are neonicotinoids degraded?
By light
In environment -> slowly
34day halflife
How are neonicotinoids absorbed, metabolized, and excreted?
Absorbed -poorly
Metabolized - liver
Excreted- bile and urine
What is the MOA of neonicotinoids ?
ACh receptor agonist -> binds to nicotinic receptors
Bind acetylcholinesterase (irreversible)
—> high levels cause overstimulation of cholinesterase -> paralysis and death
What is the toxicity of neonicotinoids to mammals and birds?
Relatively low toxicity to mammals and birds
Cannot cross BBB in mammals
What are the metabolized products of neonicotinoids ?
Charged nitrogen metabolites - potential for toxicity in non-targeted or mammalian species
Where does rotenone come from?
Plant extract - naturally in seeds and stems of several plants (vines and roots of Fabaceae plants)
Rotenone is readily degraded when exposed to??
Warm air and light
Is rotenone lipid/water soluble?
More lipophilic than hydrophilic
The GI tract and dermal absorption of rotenone is low unless ??
Mixed with fats/oils
In ingestion or inhalation more toxic for rotenone toxicity?
Inhalation
-> direct pathway to circulatory system
Where is rotenone metabolized and excreted
Metabolized - liver
Excreted - urine/feces
Rotenone is highly toxic to what species?
Fish and Arthropoda
-exposure through gills or trachea —> bloodstream and converted to highly toxic metabolites in liver
T/F: rotenone is not highly toxic to mammals and birds
True
- route of exposure is typically through gut
- broken down to less toxic metabolites before entering bloodstream
What is the MOA of rotenone?
Blocks oxidative phosphorylation in Krebs cycle
Interfere with election transport chain and ATP production
—> ROS result in oxidative stress damaging DNS and intracellular organelles —> neuronal cell death (neurotoxicity)
Dermal exposure to rotenone results in what clinical signs?
Local irritation such as conjunctivitis, congestion, and dermatitis
Oral exposure to rotenone results in what clinical sings?
GI tract irritant, convulsions, muscle tremors, lethargy, incontinence, and respiratory stimulation followed by depression
Respiratory exposure to Rotenone results in what clinical signs?
Severe pulmonary irritation and asphyxia
What are the predominate signs of rotenone toxicity?
Neurotoxin, depression, and convulsions
In the labwork, what changes would you see due to rotenone toxicity?
Hypoglycemia
Liver enzyme changes
Hypoxemia/hypercapnia
How can you diagnose rotenone toxicity?
History or documentation of exposure
What is the treatment of Rotenone?
No specific treatment- rapidly metabolized (24hrs)
Detox if appropriate
Supportive treatment (seizures, hypoglycemia)
What is the prognosis of rotenone poisoning?
Good for bird and mammals
Poor in fish, reptile, amphibians
