7: Toxicants Affecting Nervous System 2

salt toxicity mostly seen in what species?

swine and poultry

what causes DIRECT salt toxicity?

reduced water intake

what causes INDIRECT salt toxicity?

excess salt in diet

signs of salt toxicity in cattle (not as common as pigs)

edema in brain causes seizures/death

signs of salt toxicity in pigs

edema, necrosis of cerebral cortex, zone of vacuolation present on histology

unique source of salt toxicity

play-doh, paintballs

where can botulism grow?

rotting anything, improperly stored silage/roughages/hay

sign of botulism in waterfowl

limberneck (can't lift neck), respiratory paralysis

what causes botulism

clostridium botulinum

describe botulism bacterium

anaerobic, gram POSITIVE rod

how does botulism metabolize?

anaerobic conditions

how does botulism reproduce?

spores that CAN survive in AEROBIC conditions

how does botulism enter body?

ingestion (most common) or small wounds

what does botulism cleave, preventing neurotransmitters from releasing?

SNARE proteins

signs of botulism

flaccid muscle paralysis, vision changes, difficulty chewing/swallowing, paresis, death

what usually causes death with botulism?

respiratory paralysis

botulism prevents release of WHAT?

Ach

where does botulism prevent release of Ach at?

motor endplates (NMJ), autonomic ganglia, postganglionic PSNS/SNS nerves

early signs of tetanus

rigidity of masseter/facial muscles, grimacing face, moving to neck/back/abdomen

later signs of tetanus

spasms, can break bones/go into resp failure, ANS activates, causing arrhythmias, tachycardia, hypertension

what causes tetanus?

clostridium tetani

describe bacterium of tetanus

anaerobic, gram POSITIVE rod

how does tetanus metabolize?

anaerobic conditions

how does tetanus reproduce?

spores that CAN survive in aerobic conditions

incubation period of tetanus

10-14 days

species very susceptible to tetanus

horses, lambs, humans

what animals are SOMEWHAT resistant to tetanus?

dogs/cats

what species is HIGHLY resistant to tetanus?

birds

LD50 of tetanus toxin

1 ng/kg

most deadly toxin in the world

botulism

2nd most deadly toxin in the world

tetanus

tetanus pathogenesis

goes to spinal cord from NMJ, transcytoses to Renshaw cells and UMNs

MOA of tetanus

block release of glycine and GABA from INHIBITORY NEURONS, causing spastic paralysis

what does tetanus target?

synaptobrevin (on VAMP)

when teatnus reaches inhibitory neurons, what does it cleave?

SNARE PROTEIN (so also causes muscle paralysis)

goals of tetanus treatment

eliminate/neutralize toxin, control muscle ridgidity/spams, ventilative support

active immunization of tetanus uses what?

tetanus toxoid

locoweeds

oxytropis, astralagus

animals affected by locoweed

cattle, horses, sheep, elk, deer

true or false: locoweed is poisonous ALWAYS

TRUE

what is the toxic part of locoweed?

swainsonine

signs of locoweed toxicity

sudden changes in temperament, aggressiveness, ataxia, suddenly falling over

what species shows WORSE neurological effects when poisoned with locoweed?

horses

toxic principle of larkspur plant

diterpene alkaloids

diterpene alkaloids (in larkspur plant)

methyl-lycaconitine and deactylnudicauline

toxicokinectics of diterpene alkaloids

absorbed from GI tract, NOT degraded in rumen

MOA of diterpene alkaloids

compete with Ach to bind nicotinic receptors, produce reversible blockade

signs of diterpene alkaloid toxicity

muscle weakness and paralysis

toxic principle of monkshood (Aconitum spp)

polycyclic diterpenoid alkaloids

polycyclic diterpenoid alkaloids (in monkshood plant)

aconitine, tetrodotoxin

MOA of polycyclic alkaloids (monkshood)

interferes with Na channel function

toxic dose of polycyclic alkaloids (monkshood)

0.1-0.5% of animal's BW

signs of polycyclic alkaloid toxicity (monkshood)

paraesthesia, v/d, muscle paralysis, arrhythmias, cardiac arrest

signs of bromethalin toxicity

ataxia, seizure, paralysis, eventual coma

bromethalin

"brain methalin"

is there a known anidote of bromethalin?

NO

treatment of bromethalin toxicity in asymptomatic animal

induction of emesis, give activated charcoal

treatment of bromethalin toxicity in symptomatic animal

anticonvulsants (seizures), mannitol (cerebral edema)

is bromethalin toxic to humans?

YES

what animal is more susceptible to bromethalin toxicity?

CATS (2-3x more sensitive than dog)

fresh water neurotoxinsss

anatoxin-a and saxitoxin

fresh-water neurotoxins

anabaena, aphanizomenon, microcytis

fresh water hepatotoxins

microcystins and nodularins

what do microcystins do?

toxins that promote tumors

what does anatoxin-a (freshwater neurotoxin) do?

AchE inhibitor, NMB

what does saxitoxin (freshwater neurotoxin) do?

Na channel blocker

how can cyanobacteria spread to our animals?

neural, hepato, dermo, endo!!!