Pharmacokinetics III

Question 1

Describe the rates of distribution in the various tissues of the body.

Answer 1

Very rapid distribution into the gut

More slowly into the muscle because of low affinity for lipophilic drugs

High capacity - large sink, distributes much more slowly into the fat

Fat has a high affinity but is poorly perfused

Fat also has an enormous capacity for the drug

Question 2

three-compartment pharmacokinetic model

Answer 2

used to characterize the triexponential decline in plasma drug concentrations after rapid intravenous administration

drug is administered to the central volume V₁ after which it begins equilibrating with the rapidly equilibration V₂ and the slowly equilibrating V₃

volumes by volume-independent processes called intercompartmental clearances, Ci_F and Ci_S

at the same time, drug is irreversibly removed form the body by a volume-independnet process called elimination clearance, CI_E

Question 3

results of noninstantaneous drug distribution

Answer 3

termination of drug effect after a bolus or loading dose

accumulation during continuous adiministration

bolus and infusion appropriate only for drugs with high clinical margins of safety

Question 4

dose accumulation

Answer 4

if dosing intervals are not long enough to allow complete drug elimination, it will equilibrate through the body to a C_SS predicted by the dosing rate and Cl_E:

C_SS = I/Cl_E

Question 5

hydraulic model analogy

Answer 5

height of the water level in the individual buts are analogous to the drug concentration

each bucket is characterized by a cylindrical area, and the pipes connecting the buckets with each other or the outside world are characterized by a conductance G_i

water enters bucket 1 at the rate r(t) and leaks irreversibly through G₁

Question 6

How do beta-adrenergic blockades affect dosing?

Answer 6

distributes throughout the body in a flow-limited manner

slows heart rate and alters drug distribution

Question 7

pharmacodynamic lag

Answer 7

delay or inherent disconnect between arterial drug concentration and observed effect

effects onset while concentrations are decreasing

maintenance of effect when concentrations have already gone down

Question 8

biophase

Answer 8

the location where the receptors targeted by a specific drug resides