2) Pharmacokinetics Flashcards
Define pharmacokinetics:
Movement of drug into and out of the body
Define pharmacodynamics:
Drug effect and mechanism of action
Define pharmacogenetics:
Effect of genetic variability on pharmacokinetics or dynamics of drug
Describe the processes a drug goes under when it enters the body:
Absorption, distribution, metabolism, elimination
What is bioavailability?
Fraction of a dose that finds its way into a body compartment
What is the equation for bioavailability?
amount of drug reaching circulation/total drug administered
What factors affect the absorption of a drug?
Formulation
Age
Lipid or water soluble
Vomiting/malabsorption
What two factors affect bioavailability?
Absorption
First pass metabolism
What is first pass metabolism?
Any metabolism occurring before the drug enters systemic circulation
Occurs in gut lumen, gut wall and liver
What factors affect the distribution of a drug?
Protein binding
Volume of distribution
What proteins do drugs commonly bind to?
Albumin, globulins, lipoproteins and acid glycoproteins
When are protein binding drug interactions important?
If drug has high protein binding
Low volume of distribution
Narrow therapeutic window
What factors affect protein binding?
Hypoalbuminemia
Pregnancy
Renal failure
Displacement by other drugs
What is the volume of distribution?
Measure of how widely a drug is distributed in body tissues
What is the equation for calculating volume of distribution?
dose/conc of drug at T0
Give examples of drugs with a low volume of distribution:
Furosemide, warfarin
Give examples of drugs with a high volume of distribution:
Amiloride, digoxin
What are pro-drugs? Give an example:
Inactive until metabolism
L-DOPA
How is the action of cytochrome p450 influenced?
By inducers and inhibitors
Age, liver disease, hepatic blood flow, smoking and alcohol
Give examples of CYP450 isoenzymes:
CYP 2D6, 2C9, 2C19, 3A4
How does CYP2D6 vary in different populations?
Absent in 7% of Caucasians
Hyperactive in 30% of East Africans
What are the routes of elimination for a drug?
Kidneys, lungs, sweat and bile
What 3 processes determine the overall renal excretion of a drug?
GFR
Passive tubular reabsorption
Active tubular secretion
What is clearance?
Ability of body to excrete drug
Define 1st order kinetics in regard to drug elimination:
Rate of elimination proportional to drug level, half life defined
Define zero order kinetics in regard to drug elimination:
Rate of elimination is constant
How is half life calculated?
(0.693 x Vd)/Clearance
When should drugs be monitored?
Zero order, long half life, narrow therapeutic window, risk of drug-drug interactions, known toxic effects
What factors affect clearance?
Heart - blood flow to liver and kidneys
Renal and hepatic diseases
