Neurotoxicants Flashcards
1
Q
what produces the most toxic compound on the planet?
A
Clostridium botulinum
2
Q
ways to group clinical signs:
A
peripheral vs. central
excitatory vs. depressive
3
Q
organophosphate pesticides
A
- 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
4
Q
OPs mechanism of action
A
- irreversible inhibition of acetylcholine esterase activity
- cholinergic overstimulation within minutes to hours
5
Q
clinical signs of anti-esterase toxicity
A
- 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
6
Q
signs associated with muscarininc receptor overstimulation
A
SLUDGE-M
7
Q
signs associated with nicotinic receptors overstimulation
A
muscle fasiculations beginning with face, eyelids, and tongue, generalized tremors, weakness, paralysis
8
Q
signs associated with CNS overstimulation
A
respiratory depression, ataxia, nervousness, clonic-tonic seizures
9
Q
specific clinical signs associated with OP toxicity
A
- 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
10
Q
how to diagnose anticholinesterase toxicity
A
- 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
11
Q
atropine challenge
A
- 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
12
Q
treating anti-esterase toxicity
A
- 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
13
Q
OPIDN: Organophosphate-induced delayed neurotoxicity
A
- 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
14
Q
ivermectin
A
- 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
15
Q
MOA of ivermectin
A
- 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)
16
Q
Clinical signs of Ivermectin toxicity
A
- 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
17
Q
diagnosis of Ivermectin toxicity
A
- history of administration
- brain ivermectin concentrations >100ppb
- can also measure in GI content, liver, fat, feces
- no visible lesions, no diagnostic bloodwork
18
Q
treatment of ivermectin toxicity
A
- 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
19
Q
Prognosis of ivermectin toxicity
A
Good for non-susceptible breeds of dogs if exposed to <5 mg/kg but guarded at dosages > 5 mg/kg for any breed
20
Q
other rodenticides that affect the CNS
A
- Bromethalin
- Nicotine (Blackleaf 40)
- Metaldehyde
21
Q
Bromethalin
A
- Single dose rodenticide
- kills in 3-5 days so may see delayed toxicosis (trick the rats)
- parent and metabolite uncouple oxidative phosphorylation in CNS
22
Q
Nicotine
A
- Usually stimulate then block nicotinic ACh receptor
- LD50 1-2 mg/kg
23
Q
metaldehyde
A
- sources include fuel for small heaters and molluscicides
- 3-4 oz bait toxic to average size dog, sheep
- metabolized to acetaldehyde = CNS excitation
24
Q
mycotoxins
A
- Fungal metabolites which cause pathological, physiological and/or biochemical alterations usually on several organ systems
- Can affect all species
25
Q
slaframine
A
- 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
26
Q
clinical signs of Slaframine
A
-
Copious salivation (“slobbers”) primary sign
- may be the only clinical sign
- Bloat, diarrhea, frequent urination
- May see feed refusal
27
Q
Diagnosis of Slaframine toxicity
A
- Diagnosed by consumption of clover, identification of black path in clover
- Differentiate from OPs, botulism
28
Q
Treatment of Slaframine toxicity
A
- 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
29
Q
Fumonisin
A
- 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
30
Q
MOA of Fusarium
A
- 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
31
Q
Susceptible species to fumonisin
A
Susceptible species include horses, ponies, swine, and rabbits
32
Q
2 diseases linked to fumonsins
A
- Equine leucoencephalomalacia (ELEM)
- Porcine pulmonary edema (PPE)
33
Q
Porcine pulmonary edema
A
- 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)
34
Q
diagnosis of PPE
A
- 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
35
Q
Equine Leukoencephalomalacia
A
- 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
36
Q
Diagnosis of ELEM
A
- 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
37
Q
treatment of fumonisin toxicity
A
- 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
38
Q
tremorgenic mycotoxins
A
-
Fungi of genera Penicillium, Aspergillus, Claviceps
- elicit intermittent/sustained tremors in vertebrates
- sources include food, stored grains/nuts, forage for livestock, garbage, compost
39
Q
MOA of tremorgenic mycotoxins
A
release of neurotransmitters from synaptosomes in the CNS
40
Q
Clinical signs of tremorgenic mycotoxins
A
diminished activity and immobility followed by hyperexcitability, muscle tremor, ataxia, tetanic seizures, convulsions
41
Q
ammoniated feed toxicosis
A
- Non-protein nitrogen sources (urea, ammonium salts) are added to cattle feed
- Found in high concentrations in mineral licks
- Leads to excitablility “bovine bonkers”
42
Q
species affected by ammoniated feed toxicosis
A
-
bovine, caprine, ovine
- ruminants are much more susceptible
- calves can be affected though milk
43
Q
clinical signs of ammonia toxicosis/imidazoles
A
-
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
44
Q
diagnosis of ammonia toxicosis
A
- 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
45
Q
Treatment of Ammonia Toxicosis - imidazole
A
- 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
46
Q
treatment of NPN overdose toxicosis
A
- 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
47
Q
strychnine
A
- 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
48
Q
strychnine MOA
A
- 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
49
Q
clinical signs of strychnine toxicity
A
- 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
50
Q
diagnosis of Strychnine toxicity
A
- 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
51
Q
treatment of Strychnine toxicity
A
- 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
52
Q
salt toxicity
A
- water deprivation (most common) or consumption of large amounts of salt
- Most common in pigs but can be seen in cattle (or any animal)
53
Q
salt toxicity MOA
A
- 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
54
Q
clinical signs of salt toxicity
A
- 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
55
Q
diagnosis of salt toxicity
A
- 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
56
Q
treatment of salt toxicosis
A
- 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
57
Q
pharmaceuticals
A
- 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
58
Q
alprazolam (Xanax)
A
- Benzodiazepine
- One of the top 10 human medications that the ASPCA receives calls for
59
Q
MOA of alprazolam
A
Acts at the limbic, thalamic, and hypothalamic level of CNS
60
Q
clinical signs of alprazolam toxicity
A
- 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
61
Q
diagnosis of alprazolam toxicity
A
Based on suspected ingestion and clinical signs
62
Q
treatment of alprazolam toxicity
A
-
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
63
Q
zolpidem (Ambien)
A
-
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
64
Q
MOA for Zolpidem
A
- 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
65
Q
clinical signs of Zolpidem toxicity
A
Ataxia, vomiting, lethargy, disorientation, hypersalivation, hyperactivity and panting also possible
66
Q
diagnosis of Zolpidem toxicity
A
Based on suspected ingestion and clinical signs
67
Q
treatment of Zolpidem toxicity
A
- 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
