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Pharm1 Pharmacokinetics

What is clearance? The removal of a drug in units of volume/time.
Intensity of effect related... To drug concentration at receptor sites.
Duration of action related to... How long drug conc. at receptor site remains high enough to provide response.
One-compartment model easiest to use, and many drugs follow this scheme. Assumes a single compartment which is in equilibrium which accounts for drug in plasma, and various tissues.
Two (or more) compartment models more difficult to model. Seen when drug moves into tissues and is handled at different rates than central plasma compartment.
Two compartment model... Involves both distributive and elimination phases normally.I
Describe log plot of two compartment model: Log plot does not give a single straight line, but instead shows two phases.
What is zero-order kinetics? The rate is independent of the concentration.
What happens if a process (ex.- elimination) is dependent on a carrier or enzyme that may become saturated? Rate now no longer dependant on concentration, but instead becomes constant, at least until concentration falls below saturation. (Zero-order kinetics)
Bioavailability: Percentage of a drug or drug product that enters the general systemic circulation. Includes not only amount entering body, but also rate of entry.
What is the volume of distribution? The volume of distribution, Vd, is the apparent or “virtual” volume into which a drug distributes.
Can Vd be larger than the total plasma volume in the body? heparin = 5 liters (plasma only) chlordiazepoxide = 28 liters (extracellular water) imipramine = 1600 liters (highly lipid soluble)
Knowledge of the Vd is also important in estimating the... Loading dose.
About how many half-lives to reach steady-state? Five.
Drugs with a t1/2 less than 6 hours require a <blank> to use them in repeated doses. Very wide therapeutic window.
Drugs with narrow therapeutic windows should be given by... Continuous infusion.
First pass may be saturable, and like all liver metabolism may increase due to... Enzyme induction.
High Extraction Ratio: ClH controlled by blood flow rate, Strong first-pass effect, Plasma protein binding may facilitate clearance
Low Extraction Ratio: ClH controlled by intrinsic clearance, Biotransformation limited by diffusion, Plasma protein binding reduces clearance, Sensitive to enzyme inhibition and induction
Rate of renal excretion = Rate of filtration + Rate of secretion – Rate of reabsorption
For Biliary Excretion: ClB = (Conc. in bile / Conc. In plasma) Bile flow
What is normal bile flow? Bile flow normally 0.5 – 0.8 ml/min.

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