Neurotoxicants

Question 1

What is the mechanism of organophosphates?

Answer 1

It is an acetylcholinesterase inhibitor, thus it inhibits the breakdown of acetylcholine at the synapse. When ACh builds up in the synapse, over stimulation of ACh receptors occurs at both muscarinic and nicotinic receptors.

Question 2

What are the signs of organophosphate toxicity at the nicotinic receptor?

Answer 2

Muscle twitching

Question 3

What are signs of organophosphate toxcitity at the muscarinic receptor?

Answer 3

SLUDGE parasympathetic signs (Salivation, Lacrimation, Urination, Defecation, GI, Exocrine glands)

Question 4

What are general CNS signs associated with organophosphate toxicity?

Answer 4

Respiratory depression, ataxia, nervousness, clonic-tonic seizures

Question 5

What are species specific signs of organophosphate toxicity in Cats, Dogs, Horses, Cattle, and Sheep?

Answer 5

Cats: CNS stimulation progressing to convulsions. Will show more nicotinic responses than dogs.
Dogs: CNS stimulation progressing to convulsions
Horses: Colic and dehydration
Cattle: Rumen stasis without miosis and severe depression
Sheep: Severe depression

Question 6

How do you diagnose organophosphate toxicity?

Answer 6

Atropine Challenge: Administering an acetylcholine antagonist should greatly increase sympathetic effects. If you do not see sympathetic effects (mydriasis, dry mouth, increased HR), then it is likely organophosphates.
Can also Dx by clinical signs and seeing decreased RBC AChE.

Question 7

How do you treat organophosphate toxicity if it has been under 24 hours?

Answer 7

Use of Praladoximine (2-PAM) to stop the “aging” process of organophosphates.
Atropine to stop muscarinic effects
Diazepam or barbituates to stop seizures
GI decontamination/bathing to remove from skin

Question 8

What is the process behind delayed organophosphate neurotoxicity?

Answer 8

Chronic exposure causes a slow buildup of organophosphates that causes a delayed neuropathy characterized by axonal degeneration of long motor neurons. Animals will present with intact senses, but with hindlimb weakness/paralysis.

Question 9

Pathologically, what happens to the body in organophosphate toxicity?

Answer 9

Vacuolization of brain tissue

Question 10

What is the mechanism of Ivermectin toxcicity?

Answer 10

Ivermectin increases GABA release, enhances GABA binding and is a direct GABA receptor agonist causing inhibitory effects on the body and inability to respond to stimuli.

Question 11

What are the clinical signs of Ivermectin toxcicity?

Answer 11

Ataxia, disorientation, lethargy, mydriasis, coma, blindness, some bradycardia.
Recumbancy and seizures (especially in Collies)
Respiratory distress

Question 12

Where can ivermectin levels be measured?

Answer 12

Brain, GI contents, liver, fat, and feces

Question 13

How do you treat recently ingested ivermectin?

Answer 13

GI decontamination with activated charcoal - multiple doses

Question 14

What anticonvulsant would you NOT use in Ivermectin toxcicity?

Answer 14

Benzodiazepines (It’s GABA modulating effects makes the CNS inhibitory effects worse)

Question 15

What are 3 CNS affecting Rodenticides?

Answer 15

Bromothalin (mitochondrial inhibitor)
Nicotine (block of Nicotinic receptors)
Metaldehyde (metabolite acetaldehyde causes CNS over excitation. Substance that causes hangovers)

Question 16

What is the mechanism of Salaframine and where is it found?

Answer 16

Red clover mycotoxin.

It is an ACh mimic, and primarily acts as a muscarinic cholinergic agonist especially in exocrine glands = SLUDGE signs

Question 17

What are the clinical signs of Salaframine?

Answer 17

Excessive drooling “the slobbers”

Can also cause bloat, diarrhea, and frequent urination

Question 18

How do you treat Salaframine toxcicity?

Answer 18

Clinical signs abate within 48 hours of removing the clover from feed. SLUDGE signs can be treated with atropine. Maintain supportive care with fluids and electrolytes.

Question 19

What is the mechanism of Fumonisin and where is it found?

Answer 19

Metabolite of Fusarium spp. mold found on corn.
Causes inhibition of sphingosine-N-acetyltransferase causing increased levels of sphinganine, which is cytotoxic. Can affect vascular endothelial cells.

Question 20

What are clinical signs of Fumonisin in swine?

Answer 20

Cytotoxic effects on vascular endothelium causes porcine pulmonary edema and hepatic necrosis

Question 21

What are clinical signs of fumonisin in horses?

Answer 21

Cytotoxic effects targets brain and liver causing Equine Leukoencephalomalacia (equine frenzy) characterized by acute onset of anorexia, ataxia, circling, drowsiness, blindness, and hysteria that gets progressively worse.

Question 22

What is the treatment for Fumonisin toxicity?

Answer 22

There is none other than removing the contaminated feed. Swine tend to recover in 48 hours, but horses have a poor prognosis.

Question 23

What is the mechanism of tremorgenic mycotoxins and where is it found?

Answer 23

These types of mycotoxins are found in various types of mold that grow in improperly stored or spoiled food.
It causes the release of neurotransmitters from synaptosomes in the CNS leading to hyper-excitability and convulsions followed by CNS depression and paralysis.

Question 24

What do high levels of ammoniated feed cause?

Answer 24

Bovine bonkers

Question 25

How do you diagnose ammonia toxicity?

Answer 25

Analysis of feed or blood/ rumen fluid for ammonia levels (Normal blood ammonia concentration is

Question 26

How do you treat ammonia toxicity?

Answer 26

Dilute rumen ammonia by using 5-10 gallons of cold water and 1 gallon vinegar. Milk out cows so that calves don't get ammonia buildup. Remove NPN sources from feed.

Question 27

What is the mechanism of Strychnine toxicity?

Answer 27

It is a competitive antagonist of glycine (which is an inhibitory transmitter) receptors causing over stimulation of muscles.

Question 28

What are the clinical signs of Strychnine toxicity?

Answer 28

Muscle ridgidity and "sawhorse" stance followed by seizures and death from respiratory distress or exhaustion.

Question 29

How do you diagnose Strychnine toxicity?

Answer 29

Clinical signs, and chemical analysis of stomach contents. | Can also check for elevated CPK and LDH, or lactic acidosis, hyperkalemia and leukocytosis from muscle destruction.

Question 30

How do you treat Strychnine toxicity if recently ingested?

Answer 30

Must aggressively clear the substance from the system as it is rapidly absorbed: Emesis, gastric lavage, activated charcoal, fluids and forced diuresis. Ammonium chloride can be used to trap strychnine if animal is not acidotic.

Question 31

How do you treat Strychnine toxicity once signs occur?

Answer 31

Primary goal is to control seizures and prevent asphyxiation: Use of anti-seizure medication (Diazepam, phenobarbitol, methocarbamol), use of ventilator if necessary. Ammonium chloride can be used to trap strychnine if animal is not acidotic. Bicarbonate to treat acidosis.

Question 32

What is the mechanism of Na+ toxicity and how does it most commonly occur?

Answer 32

Usually happens in cases of dehydration. When sodium is concentrated in the blood, it diffuses into the CNS which causes pressure and edema from osmotic water flow.

Question 33

What are the clinical signs of sodium toxicity?

Answer 33

Salivation, increased thirst, abdominal pain and diarrhea followed by circling, ataxia, head pressing, blindness, seizures and partial paralysis.

Question 34

How do you treat sodium toxicity?

Answer 34

Slow rehydration with hyperosmotic fluids low in Na+ (Hyperosmotic so that fluid is drawn back into circulation rather than the sodium heavy CNS) Furosemide to prevent pulmonary edema from fluid therapy and to flush out sodium. Mannitol to protect kidneys

Question 35

How do you treat Alprazolam toxicity?

Answer 35

Flumazenil (GABAa antagonist), may be used for severe CNS depression associated with toxicosis, otherwise use fluid therapy and respiratory support

Question 36

What are the clinical signs of Alprazolam (Xanax) toxicity?

Answer 36

Alprazolam acts at the limbic, thalamic, and hypothalamic level of CNS causing ataxia, depression, vomiting, tremors, tachycardia, diarrhea and ptyalism (hypersalivation).

Question 37

What is the mechanism of Zolpidem (Ambien) toxicity?

Answer 37

Acts similar to benzodiazepines and binds several GABA subunits while enhances GABA signaling to inhibit neuronal excitation.