L3: Neurotoxicants (Martyniuk) Flashcards
most toxic natural substance on the planet
botulinum toxin
groupings of neurotoxin symptoms
peripheral, centrl
excitatory, depressive
strychnine
rodenticide isolated from plant
very toxic
now a restricted compound
often involved in intentional poisonings
first use of pesticides
arsenic AD 70. Has been transition from natural to synthetic pesticides
era of synthetic organic pesticides
beginning in 1940s w/ use of organochlorines (DDT), organophosphates (parathion), carbamates, dithiocarbamtes, synthetic pyrethrins.
how many pesticides in use in US?
300
what percentage of pesticide usage is non-commercial?
> 50%
Organophosphate (OP) pesticides and chars.
- parathion, malathion, chlorpyrifos
- have replaced banned organochlorine pesticides
- high water solubility and acute toxicity
OP MOA
irreversible inhibition of AChE activity –> acute ACh overstimulation
symptoms of anti-esterase toxicity
Resp. distress –> resp. m. paralysis –> death
- Muscarinic stimultion: salivation, lacrimtion, urination, defecation, GI upset, emesis, miosis (SLUDGE-M)
- Nicotinic stim: muscle fascicultions w/ face, tremors, weakness, paralysis
- CNS: resp. depression, ataxia, nervousness, clonic-tonic seizures
- last 1-5d
Horse specific symptoms of anti-esterase toxicity
colic, dehydration
Cattle specific symptoms of anti-esterase toxicity
rumen stasis. No miosis. Severe depression
Sheep specific symptoms of anti-esterase toxicity
severe depression
dogs and cats specific symptoms of anti-esterase toxicity
CNS stimulation –> convulsions
cat specific symptoms of anti-esterase toxicity with chlorpyrifos
more severe nicotinic signs. (Cats are more tolerant to muscarinic stimultion*)
dx of anticholinesterase toxicity
- Hx, CS
- Atropine Challenge: if normal signs of atropine administration (dry mouth, mydriasis, inc. HR are present, toxicity NOT due to cholinesterase inhibitor because OPs overwhelm any effect would have atropine)
- Dec. RBC AChE
- Non-specific pathology such as pulmonary edema, petechial hemorrhage in GI mucosa
tx of anti-esterase toxicity
- GI decon
- bathe for dermal exposure
- atropine sulfate for muscarinic-only signs
- oximes (protopam, 2-PAM) to reactivate AChE
- diazepam or barbiturates for seizures
- time
2-PAM is most effective for:
tx of ACUTE anti-esterase toxicity
Organophosphate-induced delayed neurotoxicity (OPIDN)
- when OP compounds produce significant inhibition of neuropathy target esterase (NTE) –> delayed neuropathy
- AChE overstimulated and neurons (esp. motor neurons) start to degenerate
- hindlimb weakness, paralysis
- NO tx
- sensory neurons more resistant
Ivermectin source and use
- produced by soil fungus Streptomyces abermitilis
- worm med
- can cross BBB in Collies, Aust. Sheps, Shelties (contraindicated!)
Ivermectin MOA in CNS
- GABA agonist
- neurotoxicant in CNS
- increased inhibitory input decreases ability to respond to other stimuli
symptoms of ivermectin toxicity
CS: mydriasis, respiratory depression, ataxia, coma, blindness, bradycardia
-anaphylactic rxns in dogs due to worm die-off
dx of ivermectin toxicity
Hx
high ivermectin conc. in brain, GI content, liver, fat, feces
no visible lesions
tx of ivermectin toxicity
GI decon if recent (act. charc, saline cathartics)
short acting barbiturate for convulsions
supportive care
EP, fluids for anphylaxis
mycotoxin
fungal metabolite which causes pathological, physiological and/or biochemical alteration usually on several organ systems simultaneously
-esp. concern for LA
aflatoxins are carcinogenic
:)
slaframine source and action
- produced by “black patch” fungus on red clover
- ACh mimic; muscarinic cholinergic agonist, esp. in exocrine glands
- most common in LA
- rarely fatal
symptoms of slaframine toxicity
copious salivation**
bloat, d, frequent urination
+/- feed refusal
dx and tx of slaframine toxicity
Dx: ID of clover w/ black patch
Tx: remove source, maintain hydration, electrolytes, atropine
fumonisin source
- metabolite of Fusarium spp. found in corn
- occurs in years of drought followed by wet weather
fumonisin MOA
- inhibition of sphingosine-N-acetyltransferase cuasing inc. levels of cytotoxic sphinganine
- affects vascular endothelial cells –> stroke, hepatic injury, pulmonary edema
susceptible species to fumonisin toxicity
equids
swine
rabbits
2 diseases linked to fumonsins
Equine leucoencephalomalacia (ELEM) Porcine pulmonary edema (PPE)
Porcine Pulmonary Edema (PPE) CS
- inactivity, inc. RR, dec. HR –> pulmonary edema –> resp. distress
- hepatic lesions
Dx of PPE
- CS + analysis of feed for fumonisin
- inc. in serum and tissue sphingoid bases
- inc. ALT, ALP, GGT, bilirubin, bile acids, cholesterol (indicators of hepatic damage)
- post-mortem pulm. path.
Equine Leukoencephalomalacia (ELEM) CS
- targets brain and liver
- anorexia, ataxia, circling, drowsiness, blindness, hysteria
- hyperexcitability, mania, profuse sweating
- hepatotoxicity
- brain liquefication
- nearly 100% mortality rate
Dx of ELEM
- CS + analysis of feed for fumonisin
- severe liver injury and lesions (elevated liver enzymes)
- post-mortem CNS necrosis and liquefaction
Tx of fumonisin toxicity
- No tx
- isolate affected animals to prevent injury to self and others
- change feed
tremorgenic mycotoxins source and MOA
- produced from fungi of genera Penicillium, Aspergillus, Claviceps, Acremonium
- MOA: release of NTs from synaptosomes in the CNS
tremorgenic mycotoxin CS
tremors, stiff gait, ataxia
2ary photosensitization, jaundice, pulm. edema
Ammoniated feed toxicosis
due to addition of non-protein nitrogens (NPN) (i.e. urea, biuret, ammonium salts) added to cattle feed such as hay
- ruminants most susceptible
- leads to “bovine bonkers”
symptoms of ammonia toxicity/imidazoles
rapid onset of: intermittent hyperexcitability w/ imidazoles SLUD convulsions inc. RR
Dx of ammonia toxicosis
Hx, CS
analysis of feed or blood/rumen fluid for ammonia lvls
inc. ammonia, glucose, BUN
dec. blood pH
Tx of ammonia toxicosis
imidazole toxicosis: No tx, remove feed (sedation, milking out cows may help)
NPN toxicosis: no specific tx (can try cold water, vinegar by stomach tube)
prognosis for imidazole vs. NPN toxicosis
imidazole: good if feed removed
NPN toxicosis: poor if recumbent
strychnine source
- seeds of Indian tree
- used to control pocket gophers
- restricted use; often used as malicious poison**
which species is resistant to strychnine?
birds
strychnine MOA
-competitive antagonist at postsynaptic spinal cord and medulla glycine receptors –> disinhibition (stimulation) of all muscles
CS of strychnine toxicity
- rapid onset
- anxiety, stiff neck/gait, “grinning”, ear twitch, sawhorse stance –> tetanic seizures –> respiratory distress/failure –> death
Dx of strychnine toxicity
- CS, lack of clonic/tonic seizures
- chemical analysis of bait, stomach contents, liver
- elevated GOT, CPK, LDH
- lactic acidosis, hyperkalemia, leukocytosis
- rule out of other seizure-causing compounds
Tx of strychnine toxicity
- control seizures and prevent asphyxiation
- emesis if no CS present yet
- gastric lavage, act. charc. forced diuresis once anesthetized
- ion trapping with ammonium chloride if not acidotic
- bicarb if acidosis develops
salt toxicity mech.
diffusion of sodium into CSF when plasma Na lvls are high. When plasma Na lvls drop, Na slowly leaves CSF which attracts water to maintain osmotic balance –> increase in CSF volume and pressure
symptoms of salt toxicity
primarily CNS (salivation, inc. thirst, abd. pain and d –> more severe CNS signs, uncoordination)
Dx of salt toxicity
high brain Na conc.
cerebral edema
rule-out polio, Pb, pesticides, encephalitis
Tx of salt toxicity
SLOW rehydration over 2-3d
IV hyperosmotic fluids low in Na
Furosemide to prevent pulmonary edema (blocks Na/K transporters so Na reabsorbed instead of excreted)**
1ary cause of pharmaceutical toxicity
careless storage
top prescribed pharmaceuticals
vicodin (pain)
synthyroid (hypothyroid)
Zocor and Lipitor (high chol.)
Lisinopril (high blood pressure)
Alprazolam (Xanax) MOA
- GABA agonist
- acts at limbic, thalamic, and hypothalamic lvl of CNS
CS of alprazolam toxicity
acute ataxia, depression, vomiting, tremors, tachycardia, diarrhea, excess salivation, hypothermia
Dx of alprazolam/Zolpidem toxicity
based on suspected ingestion and CS
Tx of alprazolam toxicity
- emesis if recent and no signs
- gastric lavage, act. charc. if ingested a LOT
- flumazenil specific antagonist
- fluids, meds to support respiration
Zolpidem (Ambien)
sleep aid; acts similar to benzos
-rapid absorption!
Zolpidem MOA
inhibits neuronal excitation by binding to the benzo omega-1 receptors
CS of Zolpidem
ataxia vomiting lethargy disorientation hypersalivation \+/- hyperactivity/panting
Tx of Zolpidem toxicity
mild: keep pet quiet and warm
- if excitement devleops, symptomatic tx
