MODULE 2 Flashcards
idiosyncratic
genetically based abnormal reactivity to a xenobiotic with no known cause
noncovalent binding
most common reaction, reversible
receptors
cellular proteins that normally serve as receptors for endogenous ligands
stereoisomers
have the same molecular formula but can have different effects
agonist
xenobiotics that bind to receptor and mimic the effect of the endogenous ligand
antagonist
xenobiotics that bind to receptor and produce no effect
partial agonist
xenobiotics that bind to receptor and produce a lesser effect than the endogenous ligand
60% of all pharmaceuticals
G protein-coupled receptors
endocrine disrupting chemicals
Nuclear hormone receptors
orphan receptors
orphan receptors are receptors with no known endogenous ligand
thiol groups are repaired by
thioredoxin and glutaredoxin
three enzymes involved in DNA repair
endonuclease, DNA polymerase, DNA ligase
fibrosis
results in excessive deposition (overproduction) of extracellular matrix proteins
most toxic ROS produced
.OH
ROS can damage cell membrane by a process called
lipid peroxidation
Xenobiotic induced proteotoxicity that causes improperly folded proteins can be repaired by
heat shock proteins
The two-electron reduction reaction that detoxifies quinones is catalyzed by
NQO
motor vehicles produce
ozone
cocaine
inhibits NE reuptake
cyanide
inhibits cytochrome c oxidase
botulinum
blocks Ach release
fluoreoacetate
inhibits aconitase
a-bungarotoxin
binds nicotinic receptors
y-hydroxybutyrate/benzodiazepines
activates GABA
dinitrophenol
donates protons to inner mitochondrial matrix
Atropine
muscarinic receptor antagonist
black widow spider venom
empties presynaptic vesicles
warfarin
inhibits activation of vitamin k channels
pentachlorophenol
causes protons to leak back into inner mitochondrial matrix
rotenone
inhibits NADH-coenzyme q reductase
tetrodotoxin
blocks Na+ channels
chlordecone
inhibits ATP synthase
CO
displaces O2 on hemoglobin
paraquat
involved in redox cycling
ethylene glycol
forms oxalate crystals
OP
inhibits AchE
DDT
overstimulates Na+ channels
colchicine
destroys microtubules involved in mitosis
PCB
AhR agonist
thalidomide
poly g promotors decrease growth factors
fluoxetine
inhibit Serotonin reuptake
modifying factors of toxicity
Age: older mammals have reduced clearance of xenobiotics increasing their toxic effects
Nutritional status: a high fat diet exposes individuals to a greater amount of legacy contaminants
Disease: a persons with a a diseases affecting the liver will have reduced clearance, increasing the toxic effect of a xenobiotic
Physical factors: mobile phone radiation may have cancer-causing effects
Social factors: crowded and isolation conditions are known to increase toxic effects
Sex: males and females have different enzymes involved in biotransformation which can lead to having a more toxic response
OP poisoning
Atropine: muscarinic receptor antagonist blocks parasympathetic effects that dominate OP poisoning
Pralidoxime: used to reactivate AChE
Benzodiazepine: anxiolytic drug used to relieve CNS anxiety and seizures
SLUDS
salivation, lacrimation, urination, defecation, sweating
OP
OPs inhibit SChE causing massive overstimulation of nicotinic and muscarinic receptors
Parasympathetic system dominates during OP poisoning
Apoptosis
Cell suicide
Active
Single cells
Cell shrinkage
Hours
Normal ATP
No inflammation
Internucleosomal DNA cleavage
necrosis
Cell murder
Passive
Cluster of cells
Cell swelling and rupture
Hours to days
Decreased ATP
Inflammation