Nicotine, Neonicotinids, And Naphthalene

Question 1

How is Naphthalene produced?

Answer 1

Combustion

• cigarette smoke
• car exhaust
• forest fire smoke

Question 2

How do mothballs act as a pesticide?

Answer 2

Slow release of naphthalene gas vapor that kills and repels moths/insects

Question 3

How do the old version of mothballs differ from the new version?

Answer 3

Old -naphthalene (highly toxic and flammable)

New- paradichlorobenzes (less toxic)

Question 4

Are cats or dogs more sensitive to naphthalene?

Answer 4

Cats

But dogs are more likely to ingest

Question 5

What is the lowest canine lethal dose of naphthalene?

Answer 5

400mg/kg

One mothball can be 2.7-4g —> single mothball can be highly toxic

Question 6

Generally, what is the exposure route to naphthalene?

Answer 6

Absorbed through inhalation, orally and dermally

Vapor can cause eye irritation

Repeated exposures can cause skin rash/cataracts

Question 7

How do oils afffect absorption of naphthalene?

Answer 7

Lipid soluble —> increase absorption

Question 8

Acids _________and bases __________ stomach absorption of naphthalene

Answer 8

Delay; enhance

Question 9

Where is naphthalene distributed after is is absorbed?

Answer 9

Bloodstream —> rapid distribution to adipose tissue

Found in high concentrations in adipose, kidney, liver, and lungs

Cross placental

Excreted in milk

Question 10

How is naphthalene metabolized?

Answer 10

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

Question 11

What is the MOA of naphthalene?

Answer 11

Oxidative metabolites in the circulation can cause hemolysis and methemoglobinemia

• hemolysis - rupture of RBC
• methemoglobinemia - decrease ability to bind oxygen —> tissue hypoxia

Question 12

What are clinical signs associated with naphthalene ?

Answer 12

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

Question 13

How can you diagnose naphthalene toxicity?

Answer 13

Hematologic changes

• hemolysis and heinz bodies
• methemoglobinemia (chocolate brown blood)
• hemoglobinuria

Question 14

What is the prognosis for naphthalene toxicity?

Answer 14

Good for those treated promptly and without pre-existing liver or kidney disease

Question 15

What is the treatment for naphthalene toxicity?

Answer 15

Decontamination

• emesis and activate charcoal
• sodium bicarb —> reduced precipitation of hemoglobin in kidney
• IVfluids

Specific treatment for methemoglobinemia

• ascorbic acid
• methylene blue 1%

Question 16

What role does ascorbic acid play in treatment of naphthalene ?

Answer 16

Reduce methemoglobin to hemoglobin (relatively slow conversion)

Question 17

How does methylene blue help treat naphthalene toxicity?

Answer 17

Leucomethylene blue is a reducing agent at low dose to make methemoglobin —> hemoglobin

Question 18

Do we use a high dose or low does of methylene blue in naphthalene toxicity?

Answer 18

Low (reducing quality)

At high doses methylene blue has oxidizing effect and can increase methemoglobin

Question 19

What does nicotine come from?

Answer 19

Water soluble alkaloid from dried eaves of tobacco plant

Question 20

How are animals exposed to nicotine?

Answer 20

Insecticides

• absorbed through the mucous membranes and respiratory tract (caustic)
• ingestion of contaminated feces

Ingestion of tobacco products (leaves, cigarettes, cigars)

Question 21

Do acids delay or enhance grastric absorption of nicotine ?

Answer 21

Delay

Question 22

How toxic is nicotine to dogs?

Answer 22

Highly toxic

oral LD50 of 9.2mg/kg

Cigarette has 9-30mg
Cigars 45-150mg

Question 23

What are the toxicokinetics of nicotine?

Answer 23

Enters the body and is distributed rapidly through the bloodstream, including CNS

Half life about 2hrs in human

Question 24

Where is nicotine metabolized and excreted?

Answer 24

Liver metabolize to cotinine and nicotine oxide

Metabolites excreted in urine

Question 25

Does renal excretion increase/decrease in an acidic urine?

Answer 25

Increase

Question 26

What is the MOA of nicotine toxicity?

Answer 26

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)

Question 27

What clinical signs are associated with nicotine toxicity?

Answer 27

Early - ataxia, lethargy - hypersalivation, vomiting - bradycardia - tremors/convulsions Late - CNS depression, tachycardia, vasodilation - paralysis of respiratory muscles (resp failure)

Question 28

How can you diagnose nicotine toxicity?

Answer 28

Observation History of exposure and clinical signs Antemortem- tox analysis of blood, vomitus, gastric contents, and urine PM- liver analysis, kidney, other tissues

Question 29

Early - ataxia, lethargy - hypersalivation, vomiting - bradycardia - tremors/convulsions Late - CNS depression, tachycardia, vasodilation - paralysis of respiratory muscles (resp failure) What is your DDx?

Answer 29

``` Strychnine Methylxanthines Tremorgenic mycotoxins Organophosphates Carbamates Depressants ```

Question 30

How do you treat nicotine/neonicotinoid toxicity?

Answer 30

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

Question 31

What is the prognosis for nicotine toxicity?

Answer 31

If animal survives the first 4 hours, prognosis is good Grave if large amounts have been ingested

Question 32

What is one of the most widely used insecticide used in the world (about 25% of all insecticide use)

Answer 32

Neonicotinoids -imidacloprid (the most widely used)

Question 33

What is the source of neonicotinioids?

Answer 33

Synthetic insecticides that are similar to nicotine

Question 34

Are neonicotinoids lipid/water soluble??

Answer 34

Water soluble

Question 35

How are neonicotinoids degraded?

Answer 35

By light In environment -> slowly 34day halflife

Question 36

How are neonicotinoids absorbed, metabolized, and excreted?

Answer 36

Absorbed -poorly Metabolized - liver Excreted- bile and urine

Question 37

What is the MOA of neonicotinoids ?

Answer 37

ACh receptor agonist -> binds to nicotinic receptors Bind acetylcholinesterase (irreversible) —> high levels cause overstimulation of cholinesterase -> paralysis and death

Question 38

What is the toxicity of neonicotinoids to mammals and birds?

Answer 38

Relatively low toxicity to mammals and birds Cannot cross BBB in mammals

Question 39

What are the metabolized products of neonicotinoids ?

Answer 39

Charged nitrogen metabolites - potential for toxicity in non-targeted or mammalian species

Question 40

Where does rotenone come from?

Answer 40

Plant extract - naturally in seeds and stems of several plants (vines and roots of Fabaceae plants)

Question 41

Rotenone is readily degraded when exposed to??

Answer 41

Warm air and light

Question 42

Is rotenone lipid/water soluble?

Answer 42

More lipophilic than hydrophilic

Question 43

The GI tract and dermal absorption of rotenone is low unless ??

Answer 43

Mixed with fats/oils

Question 44

In ingestion or inhalation more toxic for rotenone toxicity?

Answer 44

Inhalation | -> direct pathway to circulatory system

Question 45

Where is rotenone metabolized and excreted

Answer 45

Metabolized - liver | Excreted - urine/feces

Question 46

Rotenone is highly toxic to what species?

Answer 46

Fish and Arthropoda | -exposure through gills or trachea —> bloodstream and converted to highly toxic metabolites in liver

Question 47

T/F: rotenone is not highly toxic to mammals and birds

Answer 47

True - route of exposure is typically through gut - broken down to less toxic metabolites before entering bloodstream

Question 48

What is the MOA of rotenone?

Answer 48

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)

Question 49

Dermal exposure to rotenone results in what clinical signs?

Answer 49

Local irritation such as conjunctivitis, congestion, and dermatitis

Question 50

Oral exposure to rotenone results in what clinical sings?

Answer 50

GI tract irritant, convulsions, muscle tremors, lethargy, incontinence, and respiratory stimulation followed by depression

Question 51

Respiratory exposure to Rotenone results in what clinical signs?

Answer 51

Severe pulmonary irritation and asphyxia

Question 52

What are the predominate signs of rotenone toxicity?

Answer 52

Neurotoxin, depression, and convulsions

Question 53

In the labwork, what changes would you see due to rotenone toxicity?

Answer 53

Hypoglycemia Liver enzyme changes Hypoxemia/hypercapnia

Question 54

How can you diagnose rotenone toxicity?

Answer 54

History or documentation of exposure

Question 55

What is the treatment of Rotenone?

Answer 55

No specific treatment- rapidly metabolized (24hrs) Detox if appropriate Supportive treatment (seizures, hypoglycemia)

Question 56

What is the prognosis of rotenone poisoning?

Answer 56

Good for bird and mammals | Poor in fish, reptile, amphibians