Naphthalene/Nicotines/Rotenone Flashcards
Naphthalene is the toxic component of what household item?
mothballs
how many mothballs can cause a toxic reaction in dogs/cats?
just one can be highly toxic!
- 400 mg/kg lowest canine lethal dose
how are animals exposed to naphthalene?
- absorbed through inhalation, orally, dermally, vapor (eye irritation)
- won’t really be absorbed until it hits the intestine if eaten
- people keep moth balls in closet
how does pH affect the absorption of naphthalene?
- acids delay
- bases enhance
it is lipid soluble so the oils increase skin and GI tract absorption
where can we find high concentrations of naphthalene in the body?
- fat, kidneys, liver, lungs
why is naphthalene a risk for fetuses and neonates?
- crosses the placenta
- excreted in milk
how is naphthalene metabolized?
- metabolized in the liver by hepatic enzymes (CYP450)
- metabolites can for epoxides or quinones - reabsorption may cause cellular damage
- metabolites can be conjugated with glutathione to non-toxic substances
- metabolites can be conjugated with sulfate, glucoronic, or mercapturic acid for excretion
how is naphthalene excreted?
primarily through urine but also bile
what is the MOA of naphthalene?
- the oxidative metabolites (oxides) in the circulation can cause hemolysis and methemoglobinemia
- effect is cellular/tissue hypoxia
what are the main clinical signs with naphthalene?
- salivation
- vomiting
- mothball scented breath
- pale or brown gums
- methemoglobinemia, hemolytic anemia, hemoglobinuria
- weakness or lethargy
- labored breathing
- tremors and seizures
what are some things we could see in the lab with naphthalene toxicity?
- hemolysis, heinz bodies
- methemoglobinemia (blood is chocolate brown)
- hemoglobinuria
what can we use to treat severe cases of naphthalene poisoning?
methylene blue 1%
- reduces methemoglobin to hemoglobin
- make sure to use correct dose
- controversial in CATS - can case hemolysis
how is nicotine absorbed?
- readily through MM and resp tract - caustic
- absorption in GIT –> acids delay/bases enhance absorption
what dose of nicotine are clinical signs reported?
1mg/kg
*cigars have 45-150mg
how is nicotine metabolized/excreted?
- liver readily extracts nicotine from circulation
- two principal oxidative metabolites (cotinine and nicotine oxide)
- metabolites are inactive and extracted by the kidneys and excreted in urine
- -> renal excretion is decreased in alkaline or high pH - increased reabsorption
- -> renal excretion increased in acidic or low urine pH
what is the MOA of nicotine?
- potent PSNS stimulation
- cholinergic receptor agonist
- at low doses -> mimics acetylcholine and stimulates post synaptic nicotinic receptors
- at high doses –> stimulation will be followed by blockage
- stimulates CRTZ –> vomiting
what are the clinical signs associated with nicotine?
- early stimulation (ganglionic and neuromuscular)
- ataxia
- lethargy
- bradycardia
- tremors - later (or with high doses) nicotinic blockade
- CNS depression
- tachycardia
- vasodilation
- paralysis of resp muscles = RESP FAILURE
how do we treat nicotine poisoning?
- decontamination
- induce emesis/lavage
- activated charcoal
- AVOID antacids, which increase pH and DECREASE excretion/INCREASE GI absorption - enhance excretion
- diuretics/IV fluids
- lower pH of urine - atropine for parasympathetic effects
- diazepam to control seizures
what are some properties of neonicotinoids?
- water soluble
- degrades slowly in the environment
- degraded by direct light
- charged nitrogen metabolites (toxic to non target species)
what are the toxicokinetics of neonicotinoids?
- poorly absorbed
- metabolized in liver
- excreted in bile and urine
what is the MOA of neonicotinoids?
- ACh receptor agonist - binds to nicotinic receptor
- bind ACh-esterase (binding is irreversible - OPs too)
- high levels of ACh agonist and neonic-induced inhibition of cholinesterase results in overstimulation, paralysis, DEATH
neonicotinoids cannot cross the BBB in what animals?
mammals!
can cross in insects
what is rotenone only approved for as a use?
piscicide
- used by fish managers to kill unwanted fish in rivers and lakes - NOT SPECIES SPECIFIC - repopulation needed!
explain the exposure routes and metabolism of rotenone
- it is readily degraded upon exposure to warm air and light
- more LIPOphilic than hydrophilic
- GIT and dermal absorption is LOW and incomplete UNLESS mixed with fats/oils
- inhalation is more toxic - direct pathway to circulatory system
- metabolized in liver and excreted in feces/urine within 24 hours
rotenone is highly neurotoxic to what animals?
- fish and arthropods
what is the route of exposure with rotenone?
through the gills or trachea
- resp mechanism of fish directly linked to water
- rotenone passes directly into the bloodstream through the gills and is converted to highly toxic metabolites in the LIVER
why isn’t rotenone highly toxic to mammals and birds?
- route of exposure is normally through the gut
- rotenone is readily broken down to less toxic metabolites before toxic quantities can enter the blood stream
what is the MOA of rotenone?
- blocks oxidative phosphorylation in the citric acid cycle
- interferes with the electron transport chain/ATP production in mitochondria
- cellular oxygen is reduced, resulting in reactive oxygen species (ROS)
- ROS can result in oxidative stress, damaging DNA and organelles resulting in neuronal death –> NEUROTOXICITY
What are the clinical signs with rotenone toxicity?
- dermal exposure
- local irritation such as conjunctivitis, congestion, dermatitis - oral exposure
- GIT irritation, convulsions, muscle tremors, lethargy, incontinence, and resp stimulation followed by resp depression - resp exposure
- severe pulmonary irritation and asyphyxia
Generally as a neurotoxin, depression and convulsions are the main CS
what lab results might we see antemortem with rotenone toxicity?
- hypoglycemia
- liver enzyme changes
- hypoxemia/hypercapnia
what is the treatment for rotenone toxicity?
- no specific treatment (rapid metabolism - 24hr)
- detox if appropriate
- supportive treatment for seizures/hypoglycemia
