Drug Distribution Flashcards
What does drug distribution refer to?
Reversable transfer of drug between blood & extra vascular fluids + tissues
What does tissue distribution depend on?
Plasma protein binding
Tissue perfusion
Membrane characteristics
Transport mechanisms
Diseases and other drugs (esp renal failure, liver disease, obesity)
Elimination
What can be said about an unbound drug (not bound to plasma protein)?
Only unbound drug is biologically active.
What can change the amount of bound drug?
Renal failure
Hypoalbuminaemia
Pregnancy
Other drugs
When does protein binding matter?
Drug more than 90% bound
tissue distribution small
What are the parameters of the therapeutic range?
volume of distribution,
clearance
half-life
What is the volume of distribution?
Vd
Vol of plasma needed to account for total drug amount in patient
Units of litres per kg
What does a greater Vd indicate?
Increased ability to diffuse through lipid membranes
What is the Vd in theory
42L (in equal distribution in the body)
What is the definition of clearance?
Theoretical volume when drug is completely removed over a period of time
What is the measurement of clearance?
Measured in units of time (ml/min)
What does clearance depend on?
Dependent on concentration and urine flow rate for renal clearance.
Dependent on metabolism and biliary excretion for hepatic clearance.
What is the definition of half life?
Time taken for the drug conc. in the blood to decline to half of current value.
What is half life dependant on?
Volume of distribution
Rate of clearance.
What is the result of prolongation of the half life of a drug?
Will increase the toxicity of a drug.
What is drug elimination?
Removal of active drugs and metabolites from the body
Determines length of action of drug
What are the two components of drug elimination?
Metabolism (usually in the liver)
Excretion (kidney, biliary system/gut, lung, milk)
What is the primary organ for drug excretion
Kidney
What are the three main mechanisms for drug excretion by the kidney?
Glomerular filtration
Active tubular secretion
Passive tubular reabsorption
What is renal damage often a cause of?
Drug toxicity
Where are all unbound drugs filtered
Glomerulus
What happens after glomerular filtration decreased
Reduces drug clearance
Increased blood levels
Prolongation of half life
Toxicity
What is active tubular secretion
Drugs secreted into proximal renal tubule
Important to eliminate protein bound caionic/anionic drugs
what does passive tubular secretion involve
Filtrate moves down renal tubule
Any drug present is concentrated
Water is reabsorbed
Passive diffusion along conc gradient allows drug to move back through tubule into circulation
In which areas does passive diffusion occur in the kidney
Distal tubule
Collecting duct
What can effect passive tubular reabsorption
Renal failure
How much drug elimination does biliary secretion account for
5-95%
