Pharm1 Pharmacokinetics
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| What is clearance? | The removal of a drug in units of volume/time.
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| Intensity of effect related... | To drug concentration at receptor sites.
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| Duration of action related to... | How long drug conc. at receptor site remains high enough to provide response.
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| 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.
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| 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.
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| Two compartment model... | Involves both distributive and elimination phases normally.I
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| Describe log plot of two compartment model: | Log plot does not give a single straight line, but instead shows two phases.
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| What is zero-order kinetics? | The rate is independent of the concentration.
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| 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)
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| 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.
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| What is the volume of distribution? | The volume of distribution, Vd, is the apparent or “virtual” volume into which a drug distributes.
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| 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)
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| Knowledge of the Vd is also important in estimating the... | Loading dose.
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| About how many half-lives to reach steady-state? | Five.
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| Drugs with a t1/2 less than 6 hours require a <blank> to use them in repeated doses. | Very wide therapeutic window.
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| Drugs with narrow therapeutic windows should be given by... | Continuous infusion.
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| First pass may be saturable, and like all liver metabolism may increase due to... | Enzyme induction.
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| High Extraction Ratio: | ClH controlled by blood flow rate, Strong first-pass effect, Plasma protein binding may facilitate clearance
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| Low Extraction Ratio: | ClH controlled by intrinsic clearance, Biotransformation limited by diffusion, Plasma protein binding reduces clearance, Sensitive to enzyme inhibition and induction
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| Rate of renal excretion = | Rate of filtration + Rate of secretion – Rate of reabsorption
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| For Biliary Excretion: | ClB = (Conc. in bile / Conc. In plasma) Bile flow
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| What is normal bile flow? | Bile flow normally 0.5 – 0.8 ml/min.
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