Naphthalene/Nicotines/Rotenone Flashcards

1
Q

Naphthalene is the toxic component of what household item?

A

mothballs

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2
Q

how many mothballs can cause a toxic reaction in dogs/cats?

A

just one can be highly toxic!

  • 400 mg/kg lowest canine lethal dose
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3
Q

how are animals exposed to naphthalene?

A
  • 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
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4
Q

how does pH affect the absorption of naphthalene?

A
  • acids delay
  • bases enhance

it is lipid soluble so the oils increase skin and GI tract absorption

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5
Q

where can we find high concentrations of naphthalene in the body?

A
  • fat, kidneys, liver, lungs
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6
Q

why is naphthalene a risk for fetuses and neonates?

A
  • crosses the placenta

- excreted in milk

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7
Q

how is naphthalene metabolized?

A
  1. 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
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8
Q

how is naphthalene excreted?

A

primarily through urine but also bile

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9
Q

what is the MOA of naphthalene?

A
  • the oxidative metabolites (oxides) in the circulation can cause hemolysis and methemoglobinemia
  • effect is cellular/tissue hypoxia
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10
Q

what are the main clinical signs with naphthalene?

A
  • salivation
  • vomiting
  • mothball scented breath
  • pale or brown gums
  • methemoglobinemia, hemolytic anemia, hemoglobinuria
  • weakness or lethargy
  • labored breathing
  • tremors and seizures
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11
Q

what are some things we could see in the lab with naphthalene toxicity?

A
  • hemolysis, heinz bodies
  • methemoglobinemia (blood is chocolate brown)
  • hemoglobinuria
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12
Q

what can we use to treat severe cases of naphthalene poisoning?

A

methylene blue 1%

  • reduces methemoglobin to hemoglobin
  • make sure to use correct dose
  • controversial in CATS - can case hemolysis
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13
Q

how is nicotine absorbed?

A
  • readily through MM and resp tract - caustic

- absorption in GIT –> acids delay/bases enhance absorption

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14
Q

what dose of nicotine are clinical signs reported?

A

1mg/kg

*cigars have 45-150mg

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15
Q

how is nicotine metabolized/excreted?

A
  • 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
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16
Q

what is the MOA of nicotine?

A
  • 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
17
Q

what are the clinical signs associated with nicotine?

A
  1. early stimulation (ganglionic and neuromuscular)
    - ataxia
    - lethargy
    - bradycardia
    - tremors
  2. later (or with high doses) nicotinic blockade
    - CNS depression
    - tachycardia
    - vasodilation
    - paralysis of resp muscles = RESP FAILURE
18
Q

how do we treat nicotine poisoning?

A
  1. decontamination
    - induce emesis/lavage
    - activated charcoal
    - AVOID antacids, which increase pH and DECREASE excretion/INCREASE GI absorption
  2. enhance excretion
    - diuretics/IV fluids
    - lower pH of urine
  3. atropine for parasympathetic effects
  4. diazepam to control seizures
19
Q

what are some properties of neonicotinoids?

A
  • water soluble
  • degrades slowly in the environment
  • degraded by direct light
  • charged nitrogen metabolites (toxic to non target species)
20
Q

what are the toxicokinetics of neonicotinoids?

A
  • poorly absorbed
  • metabolized in liver
  • excreted in bile and urine
21
Q

what is the MOA of neonicotinoids?

A
  • 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
22
Q

neonicotinoids cannot cross the BBB in what animals?

A

mammals!

can cross in insects

23
Q

what is rotenone only approved for as a use?

A

piscicide

  • used by fish managers to kill unwanted fish in rivers and lakes - NOT SPECIES SPECIFIC - repopulation needed!
24
Q

explain the exposure routes and metabolism of rotenone

A
  • 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
25
Q

rotenone is highly neurotoxic to what animals?

A
  • fish and arthropods
26
Q

what is the route of exposure with rotenone?

A

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
27
Q

why isn’t rotenone highly toxic to mammals and birds?

A
  • 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

28
Q

what is the MOA of rotenone?

A
  • 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
29
Q

What are the clinical signs with rotenone toxicity?

A
  1. dermal exposure
    - local irritation such as conjunctivitis, congestion, dermatitis
  2. oral exposure
    - GIT irritation, convulsions, muscle tremors, lethargy, incontinence, and resp stimulation followed by resp depression
  3. resp exposure
    - severe pulmonary irritation and asyphyxia

Generally as a neurotoxin, depression and convulsions are the main CS

30
Q

what lab results might we see antemortem with rotenone toxicity?

A
  • hypoglycemia
  • liver enzyme changes
  • hypoxemia/hypercapnia
31
Q

what is the treatment for rotenone toxicity?

A
  • no specific treatment (rapid metabolism - 24hr)
  • detox if appropriate
  • supportive treatment for seizures/hypoglycemia