Toxins Flashcards
Hexachlorophene
Germicide
Spongy degeneration of WM
Penitrem A and roquefortin
Mycotoxins produced by penicillium app
Ataxia, tremors, staring
Thallium
Heavy metal found in rodenticides that are banned from use
Seizures, dementia, hyperesthesia, tremors, ataxia, paraparesis or plegia
Pyridoxine
Massive dose of vitamin B6
Sensory neuropathy- ataxia, dysmetria, decreases GP
Vincristine
Alkaloid antineoplastic agent
Impairment of axonal transport due to breakdown of neurotubules
LMN paraplegia
Salinomycin
Cats
Chicken feed ionosphere coccidiostat
Paresis, dysphasia, suspense, muscle atrophy
Anatoxin-a
Blue green algae
Potent cholinergic agonist at nACh receptors and at the NMJ
Anatoxin-a(s)
Naturally produced OP
Potent irreversible inhibitor of ACh
Charatoxin
Green algae
Competitive antagonist at nACh receptor at high concentrations
Enhances ACh binding at low concentrations
Aminoglycosides
Acute, reversible NMJ blockade mediated via calcium antagonism at external cell membrane channel site on pre and post synaptic membrane
Neomycin>kanamycin>amikacin>gentamicin>tobramycin
Polymyxins
Microorganism derives polypeptides that disrupt the structure of cell membranes and are effective for g- bacteria
primary effect on postsynaptic membrane in nondepolarizing non competitive manner
Tetracyclines
Proposed mechanisms for NMJ blockade include:
Chelation of serum calcium
Calcium antagonizing effects of the magnesium in the diluent
Post NMJ depression of muscle to the effect of ACh
Ionophores
Most of the toxic effect is thought to be mediated by disrupting the normal ion gradient of cells
Lasalocid May induce changes in the membrane potential by influencing the permeability of nerve cell membranes to cations
A-latrotoxin
Potent activation of neurotransmitter release and loss of synaptic vesicles followed by depletion of neurotransmitter and conduction block
Black widow spider
Botulism
One of the most potent known toxins
Dogs - type C1
Blocks the release of ACh at the level
of the NMJ and at cholinergic autonomic synapses
Cleaves the proteins required for neurotransmitter exocytosis
Tetrodotoxin
Selectively blocks the voltage gated Na conductance mechanism common to both nerve and muscle and this inhibits propagation of action potentials
Curare class of NMJ blocking agents - membrane stabilizing NMJ blocking agents
Post synaptic binding to nicotine cholinergic receptor and competitively blocking the action of ACh
Atracurium, vecuronium
Depolarizing NMJ blocking agents
Succinylcholine and decamthonium
Open ion channels similarly to ACh but the resultant depolarization in the end plate and adjacent area of the sarcoplasmic reticulum is persistent
Ganglion blocking agents
Block postsynaptic ion channel
Hexamethonium and trimethaphan camsylate
OP
Cholinergic syndrome - competitive and irreversible AChE inhibitors by binding to the enzyme esthetic site
OP-induced delayed polyneuropathy
Chronic encephalopathy
Carbamate insecticides
Target AChE at Ps autonomic junctions, all ganglia and NMJs
Reversible bind AChE which allows dissociation to occur more readily facilitating reactivation of AChE activity
Mojave rattlesnakes
Venoms A and B Venom A (mojave toxin) acts as non competitive Ca2+ channel blocker blocking the release of ACh and causing presynaptic block
SA rattlesnake
Crotoxin A and B
Toxin A potentiates toxicity of B
Crotoxin B blocks synaptic transmission by inhibiting the release of ACh
Coral snake envenomation
Alpha neurotoxins
Curate-like syndrome resulting in blockade of the postsynaptic neuromuscular transmission
Tick bite paralysis
Salivary neurotoxin
Interferes with ACh release at the NMJ and/or propagation of the impulse along motor axon terminals
D variabilis or andersoni
I holocyclus
Amphetamines
Monoamine release - competitive substrate for NE reuptake transporter and dopamine reuptake transporter
Induces impulse independent release of cytosolic catecholamines
Methylphenidate
Inhibits noradrenaline and dopamine reuptake at nerve terminus
Caffeine
Exact MOA unknown
May include phosphodiesterase inhibition, enhances catecholamine release, adenosine antagonism, or increased Ca entry into the cell
Permethrin
Interference with Na channels, enhanced Na ion conductance, and post synaptic GABA receptor chloride ionophore complex blockade
Cycad
BMAA - excitatory toxic MOA
Prolonged depolarization, changes in intracellular calcium concentrations, and activation of enzymatic and nuclear mechanisms of cell death
Moxidectin
Macrocyclic lactone
Binding GABA and glutamate gated chloride channels
Barbiturates
Inhibiting calcium accumulation in neural tissue, inhibition of neurotransmitter release, GABA mimetic action within the CNS
Avermectins
Macrocyclic lactone
Agonist effects at GABA chloride channel - in CNS of mammals and PNS of invertebrates
Potentiates synaptic GABA effects by enhancing its presynaptic release and enhancing the binding of GABA to postsynaptic receptors
Collie - ABCB1
Nicotine
Cholinergic receptor agonist that exhibits stimulant (low dose) and depressant (high dose) effects in PNS and CNS
May increase circulating levels of cortisol and catecholamines
Imidacloprid is a nicotine analogue
Bromethalin
Effective uncoupled of oxidative phosphorylation
Results in inadequate ATP synthesis leading to decreases sodium and potassium ion channel pump activity
Metronidazole
Binds to nRNA and inhibits protein synthesis thereby causing axonal degeneration
Selegiline
Selective, irreversible inhibitor of MAO-B and acts centrally to increase dopamine concentrations
Fluoxetine
SSRI- Serotonin syndrome from excessive serotonergic agonist on CNS and peripheral receptor
neuromuscular hyperactivity
Autonomic hyperactivity
Altered mental status
Cyproheptadine May reduce adverse effects
Venlafaxine
Bicyclic antidepressant that acts as serotonin, NE, and dopamine reuptake inhibitor
TCAs
Atropine-like anticholinergic effects
Inhibit biogenic amine (serotonin, NE) reuptake
Metaldehyde
Decreased brain serotonin, GABA, and noradrenaline
Systemic acidosis
Important cause of seizures