Organs most affected by toxins - ANSWERSTarget organs (use a lot of ATP/oxygen)
-Lungs
-Heart
-Kidneys
-Brain
-Liver
,Peripheral nerves
Toxicokinetics - ANSWERSQuantitative description of the concentration of a xenobiotic in body
-How concentration changes with time
-Has effects on duration of action
-Influenced by ADME
Toxicodynamics - ANSWERSQuantitative description of the effects of a xenobiotic
-Tissue, cellular, molecular
Measurable components of ADME - ANSWERSAbsorption - can measure administered drug and
concentration in blood
Distribution - difficult to measure (requires tissue samples that can be difficult to obtain)
Metabolism - can measure blood, but not target tissue
Excretion - can measure excreted concentration of drug
Elimination kinetics - ANSWERSRate(el) = k(el) x concentration in blood
-First order
First order elimination - ANSWERSC(t) = C(o) x e^(-kt)
t(1/2) = 0.693/k
Half Life - ANSWERS-Varies based on chemical properties
-Synthetic drugs like Asprin are designed to have a short enough half-life to allow for re-dosing
, -Bioaccumulation is usually due to increased half life
-Half life of metals in bone is extremely high (can only be removed from blood using chelation)
One-compartment model - ANSWERSAbsorption and Elimination
-Difficult to measure due to complexity/barriers
-Oral/dermal absorption increases C(a)
-Uptake from air will not alter C(a)
dC/dt = k(a)C(a) - k(el)C(1)
= rate in - rate out
Dosing/Exposure - ANSWERSSingle dose: Almost never happens
Intermittent exposure: Chance for bioaccumulation based on t1/2
-Possible to increase elimination from body, but easier to decrease exposure
-Extremely lipophilic compounds can actually be released by fat loss
Repeated dosing: Want short t1/2 to prevent accumulation to toxic levels
Continuous exposure: Doesn't happen except sometimes in air
-Concentration depends on elimination
Two-compartment model - ANSWERSC = A(e)^(-at) + B(e)^(-bt)
a (alpha) - distribution phase
b (beta) - elimination phase
Three-compartment model - ANSWERSC = A(e)^(-at) + B(e)^(-bt) + C(e)^(-yt)
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