Toxicology Mechanism of Actions Flashcards
ionophore MOA
bind and transport cations down concentration gradients -> uncontrolled ion transport leading to electrolyte imbalances -> loss of ATP in mitochondria -> cell death -> necrosis
nitrate MOA
rumen microbes convert nitrate -> nitrite -> ammonia
nitrite oxidizes Fe2+ -> Fe3+ -> methemoglobin -> hypoxia
NPN MOA
urea -> ammonia -> neuro signs
ATP depletion?
Na ion intoxiation/water deprivation MOA
rapid rehydration -> edema -> increased intracranial pressure -> decreased perfusion -> ischemia/necrosis/PEM
sulfur MOA
converted to hydrogen sulfite by ruminal microbes -> inhibit cytochrome C oxidase -> decreased ATP -> PEM
mycotoxins MOA
protein synthesis inhibitors
tremorgenic mycotoxins cross BBB -> block glycine and cause presynaptic Ach release
methylxanthines (theobromine, caffeine) MOA
-increased intracellular Ca
-release of catecholamines
allium spp MOA
oxidative damage; disulfides, thiosulfate
Hb oxidation; heinz bodies, eccentrocytes
RBC + Na/K pump damage; hemolysis
methemoglobin; hypoxia
grape/raisin MOA
unknown. tartaric acid suspected
macadamia nut MOA
unknown
xylitol MOA
depletion of ATP -> oxidation damage from ROS
hypoglycemia -> liver necrosis
NSAID MOA
inhibition of COX enzymes -> decreased PG synthesis
marijuana MOA
CB1 and CB2 agonist
meth MOA
release catecholamines
inhibit monoamine esterase
lead MOA
gamma-aminolevulinic acid -> protoporphyrin
binds to RBCs and inhibits maturation = rubricytosis, basophilic stippling
copper MOA
hepatic injury / inflammation / fibrosis; RBC oxidation and hemolysis, hyperbilirubinemia, hyperbilirubinuria, nephrosis
iron MOA
oxidative stress (fenton reaction) -> lesions in GI and liver
mercury MOA
reduced protein synthesis, lipid peroxidation (ROS), crosses BBB causing neuronal degeneration
arsenic MOA
trivalent/arsenite = interferes with krebs cycle
pentavalent/arsenate = uncouples oxidative phosphorylation
carbon monoxide MOA
forms carboxyhemoglobin = impaired cell respiration = loss of ATP = cell death
organophosphates/carbamates MOA
cholinesterase inhibiting = facilitate ACh activity
organochlorides MOA
endocrine disruptor
pyrethrins and pyrethroid (botanicals) MOA
slow opening/closing of neuronal Na channels = continued depolarization = hyperexcitability
neonicotinoids MOA
nAChR agonist = paralysis
anticoagulant rodenticides MOA
block vitamin K1 epoxide reductase = no reduction of vitamin K1 epoxide to vitamin K1 = no conversion of vitamin K dependent coagulants
bromethalin MOA
uncouples oxidative phosphorylation = decreased ATP = inhibits Na/K ATPase = increased intracellular Na = edema
choleocalciferol MOA
increased absorption of Ca and P = soft tissue mineralization
zinc phosphide MOA
inhibits cytochrome oxidase
strychnine MOA
blocks glycine in the CNS = unchecked reflexes = hyperexcitability to muscles
paraquat MOA
produces free radicals = lipid peroxidation, NADPH oxidation, mitochondrial damage
cyanogenic glycosides MOA
binds to cytochrome C oxidase and inhibits ETC = decreased ATP = cell death
toxic alkaloids MOA
neurotoxin
taxine alkaloids
depress cardiac conduction (inhibit Na and Ca channels)
cardiac glycosides MOA
inhibit Na/K ATPase = increased intracellular Ca = myocardial contraction
interferes with cardiac conduction
dieffenbachia spp MOA
formulation of calcium oxalate crystals - GI irritation, salivation
lectins MOA
ricin and ricinin inhibit ribosomal protein synthesis
giant hogweed MOA
bonds chemically to epithelium when exposed to sunlight
st johns wort MOA
involves primary photosensitization
ragwort MOA
damages the liver
bracken fern MOA
BM suppression
horses; thiaminase = thiamin deficiency
cows; ptaquiloside = hematuria
red maple MOA
hemolysis
yellow star thistle MOA
neurotoxic
russian knapweed MOA
glutathione depletion = increased ROS = oxidative damage = neuron cell death
inhibits dopamine release = parkinsons signs
lily MOA
renal tubular necrosis
black walnut MOA
laminitis
false hellebore MOA
involves cyclopamine (tetragenic alkaloid)