Neurotoxicants Flashcards
(67 cards)
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
slaframine
* 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
clinical signs of Slaframine
* **Copious salivation ("slobbers") primary sign**
* may be the only clinical sign
* **Bloat, diarrhea, frequent urination**
* May see **feed refusal**
27
Diagnosis of Slaframine toxicity
* Diagnosed by **consumption of clover**, identification of **black path in clover**
* **Differentiate from OPs, botulism**
28
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**
29
Fumonisin
* **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
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
31
Susceptible species to fumonisin
Susceptible species include **horses, ponies, swine, and rabbits**
32
2 diseases linked to fumonsins
* **Equine leucoencephalomalacia** (ELEM)
* **Porcine pulmonary edema** (PPE)
33
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)
34
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
35
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**
36
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**
37
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
38
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
39
MOA of tremorgenic mycotoxins
**release of neurotransmitters** from **synaptosomes in the CNS**
40
Clinical signs of tremorgenic mycotoxins
**diminished activity and immobility** followed by **hyperexcitability, muscle tremor, ataxia, tetanic seizures, convulsions**
41
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"**
42
species affected by ammoniated feed toxicosis
* **bovine, caprine, ovine**
* **ruminants** are much **more susceptible**
* calves can be **affected though milk**
43
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
44
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
45
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
46
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**
47
strychnine
* 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
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**
49
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**
50
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**
51
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**
52
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)
53
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**
54
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
55
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**
56
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**
57
pharmaceuticals
* **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
alprazolam (Xanax)
* **Benzodiazepine**
* One of the top 10 human medications that the ASPCA receives calls for
59
MOA of alprazolam
Acts at the **limbic, thalamic, and hypothalamic level of CNS**
60
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**
61
diagnosis of alprazolam toxicity
Based on **suspected ingestion and clinical signs**
62
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**
63
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
64
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
65
clinical signs of Zolpidem toxicity
Ataxia, vomiting, lethargy, disorientation, hypersalivation, hyperactivity and panting also possible
66
diagnosis of Zolpidem toxicity
Based on **suspected ingestion** and **clinical signs**
67
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
