What needs to happen to a drug once it has been absorbed?
Needs to be distributed to the tissue
What is drug distribution?
Refers to the reversible transfer of a drug between the blood and the extra-vascular fluids and tissues of the body
What is tissue distribution impacted by?
Plasma protein binding
Membrane characteristics (blood brain barrier, blood-testis/ovary barrier)
Diseases and other drugs
What do many drugs bind to?
Proteins such as albumin or alpha1-glycoprotein
When is the drug biologically active?
When it is unbound
What can drugs binding to proteins be described as?
What is the amount of drug bound changed by?
Saturability of binding
What does a small change in the amount of unbound drug lead to?
A massive change in the drug action, for example:
A drug that is 96% bound changes to 92%, so the amount of active drug has doubled
What is the therapeutic range?
Concentration of drug to achieve the desired therapeutic effect
What is the ability to achieve the therapeutic range affected by?
Volume of distribution
What is apparent volume of distribution (Vd)?
Volume of plasma that would be necassary to account for the total amount of drug in a patient's body, if that drug was present throughout the body at the same concentration as found in the plasma (expressed as L/kg)
What is the apparent volume of distribution (Vd) expressed as?
What is a formula that describes the apparent volume of distribution?
Vd = (total amount of drug in the body) / (drug blood plasma concentration)
What does it mean if a drug has a high volume of distribution?
It will go to the tissue
What does it mean if a drug has a low volume of distribution?
It will stay in the plasma
If the drug spread through every membrane what would the volume of distribution be (Vd)?
42L (because there are 42L of fluid in the average body)
What would the volume of distribution be if the blood cannot penetrate cells?
What would the volume of distribution be if the drug is highly protein bound?
What is clearance (Cl)?
Theoretical volume from which a drug is completely removed over a period of time (measure in units of time ml/min)
What is clearance expressed as?
What are the two kinds of clearance?
What is clearance a measure of?
What does clearance depend on?
Concentration and urin flow rate for renal clearance
Metabolism and bilary excretion for hepatic clearance
What is half life (t1/2)?
Time taken for the drug concentration in the blood to decline to half of the current value
What does half life depend on?
Volume of distribution
Rate of clearance
How many half lifes does it generally take to clear a drug?
What does prolongation of half life increase?
What could prolongation of half life be due to?
Reduction in clearance
Large volume of distribution
What does knowledge of a drugs half life allow?
Us to work out how often a drug needs to be administered
How are most drugs given to achieve their therapeutic effect?