2.1 Pharamacokinetics Flashcards
Define Pharmacokinetics
Study of the movement of a drug into and out of the body
What the body does to the drug
Define pharmacodynamics
Study of drug effect and mechanisms of action
What the drug does to the body
Define pharmacogenetics
The effect of genetic variability on the pharmacokinetics or dynamics of a drug on an individual
How does bioavailability translate or clinical practice?
Calculate correct formulation
How does estimating half life translate into clinical practice?
Allows dosing regimes to be devised
What processes occur as part of pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
What is the therapeutic window?
Range of plasma concentration in which the drug has the desired effect
Define bioavailability (F)
The FRACTION of a dose which finds its way into a body compartment, usually the circulation
What is the bioavailability for an IV bolus?
100%
What are the axis for a bioavailability curve?
X time post dose
Y plasma concentration
What does the area under a bioavailability curve represent?
Total drug exposure
How can oral bioavailability be calculated?
F = AUC oral / AUC IV
What factors affect bioavailability?
Absorption
- drug formulation, age, food, vomiting, malabsorption
First pass metabolism
What sort of drug formulation is preferable and why?
Modified release once a day
Short half life needs to be given many times a day. Immediate release may dip out of the therapeutic window
What is first pass metabolism?
Any metabolism occurring before the drug enters the systemic circulation
Name three areas where first pass metabolism can occur
Gut lumen
Gut wall
Liver
Describe the effect of first pass metabolism in the gut lumen
Affect3 by gastric acid, proteolytic enzymes, grapefruit juice
Affects benzylpenicillin, insulin, cyclosporin
Describe the action of first pass metabolism in the gut wall
P-glycoprotein efflux pumps drugs out of the intestinal enterocytes back into the lumen
Eg ciclosporin
Name a drug that is extensively metabolised in the liver
Propranolol
What are two key factors in drug distribution?
Protein binding
Volume of distribution
Which state should drugs be in to have a therapeutic effect normally?
Unbound
What causes protein binding drug interactions?
Displacement of drugs from binding sites
What factors affect protein binding?
Hypoalbuminaemia
Pregnancy
Renal failure
Displacement by other drugs
In what circumstances will changes in protein binding causing changes in drug distribution be important?
High protein binding
Low Vd
Narrow therapeutic window
Describe what happens when you add a highly bound precipitant drug (B) to drug A
More highly protein bound drug b will steal binding sites
Increase free drug a
(Increases effects of a)