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Flashcards in Neurotoxicants Deck (67):

what produces the most toxic compound on the planet?

Clostridium botulinum


ways to group clinical signs:

peripheral vs. central

excitatory vs. depressive


organophosphate pesticides

  • agricultural and residential use has increased since OCPs (degrade faster, used in flea collars, dips, fly, ant, roach baits)
  • parathion, malathion, chlorpyrifos
  • high water solubility and acute toxicity


OPs mechanism of action

  • irreversible inhibition of acetylcholine esterase activity
  • cholinergic overstimulation within minutes to hours


clinical signs of anti-esterase toxicity

  • may affect muscarinic receptors, nicotinic receptors, and CNS
  • signs may last 1-5 days
  • in acute poisoning the primary clinical signs may be respiratory distress and collapse followed by death due to respiratory muscle paralysis


signs associated with muscarininc receptor overstimulation



signs associated with nicotinic receptors overstimulation

muscle fasiculations beginning with face, eyelids, and tongue, generalized tremors, weakness, paralysis


signs associated with CNS overstimulation

respiratory depression, ataxia, nervousness, clonic-tonic seizures


specific clinical signs associated with OP toxicity

  • horses show clinical signs of colic and dehydration
  • rumen stasis in cattle, but no miosis
  • cattle and sheep commonly show severe depression
  • CNS stimulation in dogs and cats, progressing to convulsions
  • Chlorpyrifos causes more severe nicotinic signs in cats due to muscarinic tolerance


how to diagnose anticholinesterase toxicity

  • appropriate history and clinical signs
  • atropine challenge
  • decreased RBC AChE (inhibited > 50%)
  • non-specific pathology, may see pulmonary edema and petechial hemorrhage in GI mucosa


atropine challenge

  • administer pre-anesthetic dose
  • wait 15 mins to observe for normal signs of atropine (dry mouth, mydriasis, increases heart rate)
  • if observed, toxicity NOT due to cholinesterase inhibitor


treating anti-esterase toxicity

  • GI decontamination, bathing for dermal exposure
  • atropine sulfate for muscarinic signs, dose to effect 
    • will not stop nicotinic signs
  • oximes (2-PAM) can reactivate AChE 
  • diazepam or barbituates for seizures 
  • time


OPIDN: Organophosphate-induced delayed neurotoxicity

  • OP compounds that produce significant inhibition of neuropathy target esterase (NTE) may cause delayed neuropathy
  • characterized by axonal degeneration of long motor neurons
  • hindlimb weakness, paralysis
  • NO treatment



  • produced by soil fungus Streptomyces avermitilis
  • worm medication in dogs/cats
  • antihelminthic in livestock
  • dogs: 6-24 ug/kg is heartworm preventive dose but 200 ug/kg can cause ataxia, disorientation
  • collies, shepherds, shelties- 80/100 ug/kg causes toxicity because BBB does not block ivermectin


MOA of ivermectin

  • drugs act as a GABAA receptor agonist
  • increase GABA release, enhances GABA binding and is a direct GABA receptor agonist
  • Increased inhibitory input decreases ability to respond to other stimuli
  • can see cumulative toxicity with repeat doses due to long half life (2-3 days)


Clinical signs of Ivermectin toxicity

  • Onset time is hours to 1 day
  • affects CNS: ataxia, disorientation, lethargy, mydriasis, coma, blindness, some bradycardia
  • Recumbency and seizures more common in collies
  • Respiratory distress typically precedes death


diagnosis of Ivermectin toxicity

  • history of administration
  • brain ivermectin concentrations >100ppb
  • can also measure in GI content, liver, fat, feces
  • no visible lesions, no diagnostic bloodwork


treatment of ivermectin toxicity

  • GI contamination for recent exposures (multi doses of activated charcoal)
  • Supportive care including fluid and electrolyte therapy
    • epinephrine
    • short acting barbiturate for convulsions (no benzos)
  • Testing before administering higher doses of ivermectin is prudent


Prognosis of ivermectin toxicity

Good for non-susceptible breeds of dogs if exposed to <5 mg/kg but guarded at dosages > 5 mg/kg for any breed


other rodenticides that affect the CNS

  • Bromethalin
  • Nicotine (Blackleaf 40)
  • Metaldehyde



  • Single dose rodenticide
  • kills in 3-5 days so may see delayed toxicosis (trick the rats)
  • parent and metabolite uncouple oxidative phosphorylation in CNS



  • Usually stimulate then block nicotinic ACh receptor
  • LD50 1-2 mg/kg



  • sources include fuel for small heaters and molluscicides
  • 3-4 oz bait toxic to average size dog, sheep
  • metabolized to acetaldehyde = CNS excitation



  • Fungal metabolites which cause pathological, physiological and/or biochemical alterations usually on several organ systems
  • Can affect all species



  • Produced by "Black patch" fungus on red clover
    • rain, high humidity, cool weather triggers growth
  • Occurs regularly in central, south-eastern and southwestern states of the USA
    • = an ACh mimic, primarily acts as a muscarinic cholinergic agonist, especially in exocrine glands
  • Most commonly in horses and cattle


clinical signs of Slaframine

  •  Copious salivation ("slobbers") primary sign
    • may be the only clinical sign
  • Bloat, diarrhea, frequent urination
  • May see feed refusal


Diagnosis of Slaframine toxicity

  • Diagnosed by consumption of clover, identification of black path in clover
  • Differentiate from OPs, botulism


Treatment of Slaframine toxicity

  • Remove source, maintain hydration and electrolytes
  • Can treat with atropine
  • Clinical signs cease within 48 hours of the animals being removed from contaminated pasture (removal and cessation of salivation indicates direct diagnosis)
  • Rarely fatal



  • Metabolite of Fusarium spp. (important toxin is fumonisin B1)
  • Found almost exclusively on corn
  • Usually occurs in years of drought followed by wet weather
  • Presence of Fusarium spp. is not indicative of fumonisin


MOA of Fusarium

  • Acts by inhibition of sphingosine-N-Acetyltransferase causing increased levels of spinganine, which is cytotoxic
  • Also affects vascular endothelial cells leading to stroke, hepatic injury, and pulmonary edema


Susceptible species to fumonisin

Susceptible species include horses, ponies, swine, and rabbits


2 diseases linked to fumonsins

  • Equine leucoencephalomalacia (ELEM)
  • Porcine pulmonary edema (PPE)


Porcine pulmonary edema

  •  CS: inactivity, increased RR, and decreased HR
  • signs occur about 12 hours before development of pulmonary edema
  • Develop lethal pulmonary edema within 4-7 days of consuming contaminated feed
  • Respiratory distress, manifested as increased RR and effort with abdominal and open mouth breathing, occurs within hours of death (cyanosis of MM)


diagnosis of PPE

  • Analysis of feed for fumonisin in conjunction with clinical signs
  • An increase in serum and tissue sphingoid bases is one of the earliest and most specific biochemical change
  • Increase liver enzymes, total bilirubin, bile acids, and cholesterol
  • Post-mortem pulmonary pathology, indicating pulmonary edema, hepatic lesions, necrosis


Equine Leukoencephalomalacia

  • Most common in late/early winter
  • Main target is brain and liver 
    • acute onset of CNS signs that get progressively worse over hours
    • Hyperexcitability, mania, profuse sweating are terminal signs
  • Hepatotoxicity
    •  jaundice, hepatic encephalopathy
    • coma and convulsions from hepatic encephalopathy are terminal)
  • Nearly 100% mortality rate


Diagnosis of ELEM

  • Analysis of feed for fumonisin in conjunction with CSs
  • Severe liver injury and lesions
    • elevated liver injury and lesions
    • increased liver enzymes such as ALP, ALT, sorbitol dehydrogenase, GGT, and total bilirubin and bile acids
  • Post-mortem CNS necrosis and liquefaction


treatment of fumonisin toxicity

  • No treatment available
  • Isolate affected animals to prevent injury to themselves and others
  • Change feed
  • Pigs usually recover within 48 hours of removing contaminated feed


tremorgenic mycotoxins

  • Fungi of genera Penicillium, Aspergillus, Claviceps
    • elicit intermittent/sustained tremors in vertebrates
    • sources include food, stored grains/nuts, forage for livestock, garbage, compost


MOA of tremorgenic mycotoxins

release of neurotransmitters from synaptosomes in the CNS


Clinical signs of tremorgenic mycotoxins

diminished activity and immobility followed by hyperexcitability, muscle tremor, ataxia, tetanic seizures, convulsions


ammoniated feed toxicosis

  • Non-protein nitrogen sources (urea, ammonium salts) are added to cattle feed
  • Found in high concentrations in mineral licks
  • Leads to excitablility "bovine bonkers"


species affected by ammoniated feed toxicosis

  • bovine, caprine, ovine
    •  ruminants are much more susceptible
    •  calves can be affected though milk


clinical signs of ammonia toxicosis/imidazoles

  • Hyperexcitability
    • nervousness, rapid blinking, dilated pupils, trembling, ataxia, rapid respiration, SLUD, tonic convulsions induced by stimuli
  • Animals will alternate between hyperexcitability and "normal" behavior if caused by imidazoles
  • rapid onset
    • 15 mins to several hours (death within 24 hours)
    • for ammonia toxicity, death occurs when blood ammonia >2 mg/dl


diagnosis of ammonia toxicosis

  • Hx of exposure
  • Clinical signs very important
  • Differentials: OP pesticides, cyanide, grain overload, meningitis, encephalitis
  • Analysis of feed or blood/rumen fluid for ammonia levels
  • Increased ammonia, glucose, BUN, and decreased blood pH may help diagnose NPN ovedose


Treatment of Ammonia Toxicosis - imidazole

  • No treatment, just feed removal
  • sedation may help prevent self-mutilation
  • milking out cows that have affected calves
  • prognosis is good in adults if feed is removed quickly


treatment of NPN overdose toxicosis

  • No specific treatment
  • can try giving 5-10 gallons of cold water and 1 gallon vinegar by stomach tube
    • cold reduces urease activity and vinegar acidifies the rumen to convert ammonia to less absorbable form
  • prognosis is poor for recumbent animals



  • from seeds of Strychnos-nux vomica
  • Alkaloid used to control pocket gophers
  • Restricted-use pesticide
  • Often used as a malicious poison
  • LD50 ranges from 0.5-3 mg/kg, birds are higher


strychnine MOA

  • Rapidly absorbed and distributed in blood, liver, kidney
  • Rapidly eliminated - complete in 48-72 hours
  • Competitive antagonist at postsynaptic spinal cord and medulla glycine receptors
  • Glycine is an inhibitory transmitter, so antagonism results in disinhibition (stimulation) of all muscles


clinical signs of strychnine toxicity

  • Rapid onset (10-120mins) with little to no vomiting
  • Begins with anxiety, restlessness, stiff neck and gait, "grinning" as facial muscles stiffen, ears twitch
  • Proceeds to violent tetanic seizures initiated by external stimuli, frequency increases with time, respiratory distress
  • Sawhorse stance, rigid extension of all 4 limbs
  • Death from respiratory failure (asphyxiation during seizure), exhaustion


diagnosis of Strychnine toxicity

  • clinical signs - tetanic seizures and sawhorse stance
  • hyperthermia in dogs
  • chemical analysis of bait, stomach contents, liver
  • Elevated CPK and LDH in serum
  • Lactic acidosis, hyperkalemia and leukocytosis common lab findings
  • Rule out other compounds that can cause seizures


treatment of Strychnine toxicity

  • Primary goal is to control seizures and prevent asphyxiation
  • Administer phenobarb or methocarbamol
  • Emesis before any signs, gastric lavage once anesthetized - follow with activated charcoal and forced diuresis. MUST BE AGGRESSIVE
  • Ion trapping with ammonium chloride can be used to trap strychnine if animal is not acidotic
  • If acidosis develops, treat with bicarbonate


salt toxicity

  • water deprivation (most common) or consumption of large amounts of salt
  • Most common in pigs but can be seen in cattle (or any animal)


salt toxicity MOA

  • Mechanism is diffusion of sodium into CSF when plasma Na levels are high
  • When plasma Na levels drop, sodium leaves CSF slowly, attracting water to maintain osmotic balance
    • this increases CSF volume and pressure


clinical signs of salt toxicity

  • Primarily CNS and include salivation, increased thirst, abdominal pain and diarrhea
  • Progressing over several days into: circling, wobbling, aimless wandering, head pressing, blindness, seizures and partial paralysis
  • Cattle may be beligerent and uncoordinated
  • Toxicity is about 2.2 g/kg in swine, equine, and bovine


diagnosis of salt toxicity

  • Na levels > 160 meq/L, especially if CSF>serum
  • Brain Na >2000 ppm is diagnostic in swine and cattle
  • Differentiate from polio, lead, pesticides, encephalitis


treatment of salt toxicosis

  • Slow rehydration (over a 2-3 day period)
  • Serum sodium levels should be lowered at a rate of 0.5-1mEq/L/hour
  • IV hyperosmotic fluids low in Na
  • Loop diuretic (furosemide) can be administered to prevent pulmonary edema during fluid therapy



  • Neuroactive substances - sleeping aids and anti-depressants
  • careless storage is the primary cause
  • top prescribed include Vicodin,Synthyroid, Zocor and Lipitor, Lisinopril
  • clinical signs can be similar to human toxicity


alprazolam (Xanax)

  • Benzodiazepine
  • One of the top 10 human medications that the ASPCA receives calls for


MOA of alprazolam

Acts at the limbic, thalamic, and hypothalamic level of CNS


clinical signs of alprazolam toxicity

  • ataxia, depression, vomiting, tremors, tachycardia, diarrhea, and ptyalism
  • dangerously low body temp can also be present
  • signs usually appear within 30 mins of ingestion
  • some animals may show CNS excitation


diagnosis of alprazolam toxicity

Based on suspected ingestion and clinical signs


treatment of alprazolam toxicity

  • include standard decontamination procedures:
    • induce emesis with apomorphine if the ingestion is recent and no signs are present
    • Use gastric lavage with activated charcoal if toxic dose
  • flumazenil may be used for severe CNS depression associated with toxicosis
  • close monitoring is needed
  • additional treatment includes fluids and medications to support respiratory function


zolpidem (Ambien)

  • Sleep aid that acts in a similar way as the benzodiazepines
    • non-benzo hypnotic drug
  • Another top 10 human medication that the ASPCA receives calls for


MOA for Zolpidem

  • inhibits neuronal excitation by binding to the benzo omega-1 receptor
  • rapid absorption from GI tract and highly bioavailable
    • clinical signs typically resolve by 12 hours in dogs


clinical signs of Zolpidem toxicity

Ataxia, vomiting, lethargy, disorientation, hypersalivation, hyperactivity and panting also possible


diagnosis of Zolpidem toxicity

Based on suspected ingestion and clinical signs


treatment of Zolpidem toxicity

  • Treatment is supportive and symptomatic
    • for mild signs, keep the pet quiet and in a safe place may be enough
    • if excitement develops, symptomatic treatment should be given and will vary with the signs and their intensity