Pharmacokinetics Flashcards
What is pharmacodynamics?
What the drug does to the body.
Time course for the drug effect.
PD is important in determining the change in drug effect due to PK changes.
What is clinical pharmacokinetics?
Clinical pharmacokinetics is the application of pharmacokinetic and pharmacodynamic principles to the safe and effective therapeutic management of an individual person.
What is the one compartmental model?
Assumes drug distributes instantaneously throughout the body & equilibrates instantaneously between tissues.
What is the two compartmental model?
Assumes drug does not achieve instantaneous distribution, i.e. equilibrium, between compartments.
Slower drug distribution.
What is first order drug elimination?
Amount of drug eliminated in a set amount of time is directly proportional to amount of drug in the body.
Fraction of drug eliminated per unit time is constant.
Change in drug dose – proportional change in the drug concentration-time profile in the body.
More predictable changes in plasma concentration during dosage adjustment.
What is zero order drug elimination?
Amount of drug eliminated does not change with amount of drug in the body.
Change in dose – disproportional change in the drug concentration-time profile in the body.
More unpredictable.
Narrow therapeutic window, higher end of dosage range.
What is the volume of distribution?
Volume of fluid in which total amount of drug needs to be distributed to give a concentration equal to the measured plasma concentration.
Relates to:
Partitioning of drug between plasma and tissues.
Lipid vs water solubility.
Extent of drug plasma protein binding.
Used to calculate loading dose.
What factors affect volume of distribution?
Liver, renal, cardiac impairment. Reduced blood perfusion to tissues. Changes in plasma protein binding. Odema, ascites. Old age. Pregnancy.
What are the main routes of drug elimination:
Excreted unchanged (kidneys) and metabolism (usually liver).
Define clearance:
Clearance is the volume of plasma emptied of drug per unit time Lh-1
Clearance alters:
Drug-drug interactions.
Cardiac output.
Hepatic and renal impairment.
Plasma protein binding.
At steady state: rate in = rate out
Rate administration = rate elimination
Decrease in clearance means slower rate of elimination.
Leading to dosage adjustment.
Thus clearance determines the maintenance
dose.
What is the Elimination Rate Constant (K)
K is fraction of drug eliminated from compartment per unit time (h-1).
1st order elimination.
Amount drug eliminated decreases as plasma conc. decreases but the fraction of drug eliminated is constant.
K determines the rate of elimination.
Elimination rate = K x A (A = total amount drug in body).
Units of elimination rate: mgh-1.
What is half-life?
Time taken for plasma drug conc to fall by half what it was at beginning of measurement period .
When is TDM important?
Drug has a narrow therapeutic window.
Good concentration-response relationship.
No easily measurable physiological parameters.
To monitor compliance.
To confirm toxicity.
What are some criteria for TDM?
Narrow therapeutic window.
Pharmacokinetic variability.
Genetic factors, concurrent disease, multiple drug therapy.
Non-compliance, poor bioavailability.
Unusually rapid elimination.
Pharmacodynamic resistance to the drug.
Why do you need to optimize drug dosing regimen?
Suitable doses at a frequency which ensures maintenance of steady state plasma conc. within the therapeutic window, for entire duration of therapy.