MODULE 1 Flashcards
Paracelsus
dose define the poision
toxicokinetics
what the body does to the xenobiotic
toxicodynamics
what the xenobiotic does to the body
summation
2+2=4
synergism
2+2=10
potentiation
0+2+10
antagonism
2+2=0
clearance
overall efficiency of xenobiotic removal from body
bioaccumulation
the net accumulation of xenobiotic in an organism from all exposure routes
bioconcentration
net accumulation of a xenobiotic in on organism is from water only
biomagnification
occurs when xenobiotic concentrations increase through at least three trophic levels
weak acid
more non-ionized
diffused into tissue
weak base
more ionized
become trapped
most important property
lipophilicity
most common absorption pathway
passive diffusion
active transport
ATP-binding cassette
facilitated diffusion
OAT family
relative lipid solubility
octanol-water partition coefficient
only form that can passively diffuse
nonionized form
most abundant plasma protein binding protein
albumin
detoxification
biotransformation results in a less toxic metabolite
bioactivation
biotransformation results in more toxic metabolite
High and very low metabolism in organs
High- liver
very low- brain
Phase 1
Cytochrome P450-dependent monooxygenases
cytochrome P450 reductase
Cofactor: NADPH
Glucuronidation
enzyme: UDP-glucuronsoyl transferase
cofactor: UDP-glucuronic acid
Sulfation
enzyme: sulfotransferase
cofactor:PAPS
Acetylation
Enzyme: N-acetyltransferase
Cofactor: acetyl coenzyme A
Glutathione
Enzyme: glutathione S-transferase
Cofactor: glutathione
methyl mercury
neurotoxic environmental toxicant
CYP3A4
human liver
paracellular
small molecules can cross cellular membranes
Excretion
glomerular filtration, tubular reabsorption, tubular secretion
tubular secretion
movement of xenobiotics into kidney filtrate
enterohepatic cycling
Xenobiotics excreted in the bile into intestine can be reabsorbed and distributed back to the liver (increase half-life)
most important excretion route
renal excretion
acid-base equation
What would be more preferentially absorbed from the stomach
(pH=2): a weak acid with pKa=3 or a weak acid with a pKa=4?
Log [HA]/[A-] = 3-2 = 1
Take antilog: [HA]/[A-] = 10
Log [HA]/[A-] = 4-2 = 2
Take antilog: [HA]/[A-] = 100
bioavailability
the fraction of an orally administered drug that reaches the systemic circulation in an unchanged form
bioavailability short answer
The humans had a pH that resulted in the drug being less non-ionized and readily absorbed
The humans had higher amount of plasma binding proteins decreasing the half-life of the xenobiotic
The human subject had a polymorphism that resulted in being a poor metabolizer
The human subject had a disease that increased the half-life of the xenobiotic
rats vs mice
One species is a poorer glucoronidators, meaning that some xenobiotics would stay in the body longer resulting in more toxic effects
One species was younger or older than the other species who have lower enzyme activities
One species was feed a diet that resulting in inhibition of CYP enzymes (decrease biotransformation of xenobiotics
The mice went through bioactivation resulting in a more toxic metabolite
The mice had a different pH of the stomach than rats
The mice had less albumin present resulting in freer xenobiotic in their system than plasma bound xenobiotics
The mice underwent enterohepatic cycling of the xenobiotic, increasing the half-life of the xenobiotic
