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Neurotoxicology
N/A
65
Pharmacology
Professional
02/09/2013

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Term
Functional range of neurotoxicities
Definition
Cognitive, Motor, Sensory, Mood/Personality, General
Term
Classes of neurotoxicants
Definition
Pharmaceuticals, Chemicals, Neurotoxins
Term
REMEMBER THIS PHONE NUMBER FOR POISON CONTROL
Definition
1-800-222-1222
Term
produced by living organisms
Definition
neurotoxins
Term
from plant or animal
Definition
exogenous
Term
we make within our own bodies
Definition
endogenous
Term
the most lethal toxin of any known animal (exogenous)
Definition
Batrachotoxin
Term
Batrachotoxin
Definition
opens neuronal sodium channels so cell membrane is no longer polarized and can no longer transmit impulses
Term
Tedrotoxin
Definition
blocks sodium channels from passing sodium --> paralysis and respiratory arrest within minutes --> cardiac arrest due to lack of oxygen
Term
Exogenous Toxins
Definition
Batrachotoxin, Tetrodotoxin
Term
Endogenous Toxin
Definition
Glutamate
Term
Glutamate-induced excitotoxicity
Definition
overactivation of receptors for excitatory amino acid transmitters lead to cell damage and death
Term
Normal conditions: role of glutamate
Definition
activates NMDA and AMPA receptors resulting in an influx of both Na and Ca ions, depolarization --> action potential
Term
Excitotoxicity: role of glutamate
Definition
results in high intracellular levels of calcium ions resulting in neuronal death
Term
Massive activation of NMDA receptors
Definition
dramatic increase in cytosolic calcium, which is taken up by the mitochondria
Term
Mitochondrial calcium overload
Definition
leads to explosion of oxygen production and the subsequent release of cytochrome C
Term
High cystolic calcium activates nNOS and increases NO production
Definition
oxygen and NO react to produce ONOO-, which then diffuses into the nucleus to cause DNA damage
Term
results in release of glutamate, eating away at neurons
Definition
spinal cord injury
Term
when certain parts of brain are deprived of oxygen, results in excessive release of glutamate
Definition
stroke
Term
have implicated glutamate in the pathophysiology
Definition
ALS, MS, Alzheimers, Parkinsons, Huntingtons, Alcohol withdrawal
Term
Transmission, Axonopathy, Myelinopathy, Neuronopathy
Definition
types of neurotoxicity
Term
drug-induced transmission toxicity
Definition
organophosphate poisoning; cocaine intoxication; nicotine-induced brain damage
Term
inhibits AChE so buildup of unhydrolyzed ACh continues transmitting nervous signals to muscles
Definition
Sarin
Term
inhibition of DA and NE transporters; overactivation of DA and alpha adrenergic receptors centrally and peripherally
Definition
Cocaine-intoxication
Term
induces ROS levels in a dose-dependent manner and activates a NF-kb involved in biological processes (inflammation, innate immunity, development, apoptosis)
Definition
Nicotine
Term
Nicotine activates a mitogen-activated protein kinase (MAPK) which is involved in the cellular apoptosis pathway
Definition
c-Jun terminal kinase (JNK)
Term
Significantly smaller grey matter and lower grey matter density in front regions, occipital lob and temporal lobe
Definition
in smokers
Term
drug-induced axonopathy
Definition
organophosphates, cisplatin, vincristine
Term
similar to ALS; usually starting distally and progression towards the neuron
Definition
Drug-induced axonopathy
Term
occurs 1-5 weeks following severe intoxication
Definition
Organophosphates-induced delayed neuropathy (OPIDN)
Term
organophosphates inhibit this to cause symmetrical sensory-motor degeneration of peripheral nerves and spinal cord
Definition
neuropathy target esterase (NTE)
Term
symmetrical sensory-motor degeneration of peripheral nerves and spinal cord
Definition
--> muscle weakness, ataxia and subsequent paralysis of the limbs
Term
NTE
Definition
deacylates the major neuronal membrane phospholipid, phosphatidylcholine
Term
produces damage to the organ of Corti,including the destruction of auditory sensory cells
Definition
Cisplatin
Term
begins 3-4 days after Cisplatin toxicity;
Definition
Ototoxicity
Term
symmetrical peripheral axonal sensorimotor neuropathy early in therapy
Definition
--> paresthesia and severe motor weakness
Term
interferenece with microtubule, affecting axonal transport
Definition
vincristine-induced sensorimotor neuropathy
Term
interference with salutatory conduction or the facilitated propagation of action potentials along myelinated axons
Definition
drug-induced myelinopathy
Term
produce myelin
Definition
Schwann cells
Term
drug-induced myelinopathy
Definition
may progress to axonopathy
Term
Lead-induced neurotoxicity, hexachlorophene-induced spongiform encephalopathy, nitrous oxide-induced myelinopathy, carbon monoxide-induced encephalopathy
Definition
drug-induced myelinopathy
Term
primary target is the CNS; diff. mechanisms include oxidative stress, intensification of apoptosis of neurons, interfering with Ca-dependent enzyme like nitric oxide synthase
Definition
Lead-induced neurotoxicity
Term
inhibit respiratory D-lactate dehydrogenase and interfere with the electron transport chain
Definition
hexachlorophene
Term
Hexachlorophene
Definition
mitochondrial neurotoxin especially toxic to developing oligodendrocytes
Term
myelin with water-filled spaces or vacuoles (spongiform encephalopathy)
Definition
biomarker for hexachlorophene effects
Term
irreversibly oxidizes cobalt ion in methylcobalamin and inhibits the synthesis of methionine
Definition
nitrous oxide
Term
Lack of S-adenosylmetionine
Definition
impairs methylation of myelin sheath phospholipids --> reduction in myelin formation
Term
causes endothelial and platelet release of NO and formation of oxygen free radiccals including peroxynitrite
Definition
carbon monoxide
Term
causes delayed but reversible demyelination of white matter, which can lead to edema and necrosis
Definition
Lipid peroxidation
Term
Irreversible neuronal loss peripherally or centrally
Definition
Neuronopathy
Term
neuronopathy clinical disease state
Definition
Alzheimer's disease
Term
twisted fragments of protein
Definition
neurofibrillary tangles
Term
amyloid plaques
Definition
abnormal clusters of amyloid and tau protein remnants
Term
drug-induced neuronopathy
Definition
MPTP-induced parkinsonism, Methylmercury-induced neuropathy, Arsenic-induced neurotoxicit, Streptomycin-induced ototoxicity
Term
a by product of MPP synthesis
Definition
MPTP
Term
MPTP--> MPP+
Definition
taken up into dopamine neurons
Term
attacks the mitochondrion and inhibits energy production, causing neuronopathy and a syndrome resembling advanced parkinsonism
Definition
MPP+
Term
organic form of mercy and the form of mercury that is most easily bioaccumulated
Definition
MeHg
Term
major source of human exposure to MeHg in the U.S.
Definition
consumption of contaminated fish
Term
cerebral palsy, blindness, deafness, growth problems, mental retardation, microcephaly
Definition
Minamata disease
Term
reacts with the thiol groups of proteins and enzymes and inhibits their catalytic activity
Definition
Arsenic
Term
causes changes in the cytoskeletal protein composition and hyper-phosphorylation
Definition
Arsenic-induced Neurotoxicity
Term
key mechanism of As-induced neuronopathy
Definition
disorganization of the cytoskeletal framework
Term
disruption of mitochondrial protein synthesis and the formation of free oxygen radicals
Definition
Aminoglycoside ototoxicity
Term
out of the all ototoxic drugs, these are the most vestibulotoxic
Definition
Aminoglycosides
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