Mechanisms only Flashcards
organophosphate pesticides (OPs)
irreversible inhibition of acetylcholinesterase (AChE) activity = anticholinesterase
ivermectin
GABA receptor agonist (depressive effects)
pyrethroid pesticides
binds voltage gated Na+ channel (excitation)
bromethalin
damages mitochondrial function (uncouples oxidative phosphorylation in CNS) -> loss of ion gradient ->fluid accumulation in myelin sheaths -> decreased nerve conduction and respiratory arrest
(CEREBRAL EDEMA)
alprazolam (xanax)
GABA receptor modulator that acts at the limbic, thalamic, and hypothalamic level of the CNS (depressive effects)
zolpidem (ambien)
inhibits neuronal excitation by binding to the benzodiazepine site of GABA receptors (depressive effects)
slaframine
muscarinic cholinergic agonist (ACh mimic) especially in exocrine glands
(SLOBBERS)
fumonism
inhibits sphingosine-N-acetyltransferase causing increased levels of sphinganine which is cytotoxic
(CORN)
strychnine
competitive antagonist at post synaptic spinal cord and medulla glycine receptors; glycine is an inhibitory neurotransmitter, therefore evokes an overstimulation (excitation)
salt
diffusion of sodium into CSF when plasma sodium levels are high leading to inhibition of glycolysis and ATP and attraction of water
(Na+ >160 mEq/L)
phenoxyacetic acid herbicides
mechanism unknown
ergot alkaloids
dopamine and serotonin receptor agonists
ionophores
increase intracellular Na+ and Ca++, leading to mitochondiral swelling and cell death, especially in muscle. remember it’s target is the mitochondiral MEMBRANE)
(heart problems)
tetanus
blocks release of GABA and glycine (both are inhibitory neurotransmitters) resulting in overstimulation of muscles resulting in stiffness
anticoagulants
inhibits vitamin K1 epoxide reductase, preventing formation of vitamin K dependent clotting factors
nitrates
nitrate->nitrite->vasodilation and ferrous iron + Hgb -> methemoglobin ->oxygen starvation of tissues
cardiac glycosides
inhibits Na+/K+ ATPase through competition with K+ for binding sites
cyanide
inhibition of cytochrome oxidase and oxidative phosphorylation
methylxanthines
competitive antagonist of adenosine receptors (causes CNS stimulation, vasoconstriction, tachycardia); prevents Ca++ reuptake, leading to increased skeletal and cardiac muscle contractility
gossypol
chelates iron and causes anemia, inhibits dehydrogenase leading to decreased energy and stress (can be cumulative as it is lipophilic)
cantharidin
inhibits protein phosphatases (dysregulates protein metabolism); mucosal irritant
(muzzle in the water)
ethylene glycol
major toxic agents of ethylene glycol are metabolites produced by the action of alcohol dehydrogenase; glycolic acid causes acidosis, glyoxilic acid thought to cause CNS signs, oxalate/oxalic acid causes renal damage and hypocalcemia
cholecalciferol/vitamin D3
causes massive increases in serum Ca++ by increasing GI absorption, decreasing renal excretion, increasing synthesis of calcium binding protein, mobilizing bone calcium
grape/raisin
unknown
acetaminophen
formation of NAPQI causes liver tissue necrosis and increased methemoglobin, oxidative damage of erythrocytes in cats (methemoglobin and heinz body production)
NSAIDS
uncoupled oxidative phosphorylation at high doses, blocks COX-1 and COX-2 decreasing prostaglandins
arsenic
depends on the form
- pentavalent (CNS signs): reduced and metabolized in rumen, reduces to metabolic energy and some is converted to trivalent form
- trivalent (blood): binds to -SH groups -> disrupts cellular metabolism and inhibits oxidative phosphorylation
zinc
free zinc is released in the stomach’s acidic environment forming zinc salts leading to corrosive effect to stomach and intestinal mucosa; oxidative damage
phenols
denatures and precipitates cellular proteins thus destroying all contacted cells
zearalenone
estrogen receptor agonist
think pig vulva
bee venom
mellitin (latin for SWEET/HONEY) causes pain and histamine release, phospholipase A2 destroys membranes
wasp/hornet venom
some contain neurotoxins, kinins induce pain
ant venom
peperidine causes dermal necrosis and formic acid causes burnign sensation and pain
holocyclotoxin (tick saliva)
impairs acetylcholine release at neuromuscular junction (results in weakness and paralysis)
other mechanism associated with dermacentor toxin
acts on Na+ channels
toad poisoning
secretions from the toad include biogenic amines (histamines) and Bufogenins (bufotalin)
bufogenins (bufotalin)
inhibit Na+/K+ ATPase, produce cardiac arrhythmias
SIMILAR TO CARDIAC GLYCOSIDES AND TX SIMILARLY!
alpha-Iatrotoxin (black widow)
creates pores in membranes allowing Ca++ entry and releasing massive amounts of neurotransmitter ->sustained muscle spasms
sphingomyelinase D (brown recluse)
binds to cell membranes and cleaves heads off lipids
eastern coral snake venom
bungarotoxin is a neurotoxin that prevents binding of Ach, causing paralysis
enterotoxins from garbage/carrion toxicity
bind to intestinal epithelium, increasing permeability and causing fluid loss (diarrhea) and decreased absorption of nutrients
endotoxins
LPS - gram negative cell walls
botulinum
prevents release of ACh at neuromuscular junction causing paralysis
