Distribution Flashcards
What is distribution?
The process of reversible transfer of drug from the bloodstream to other areas of the body
What is rate and extent of distribution determined by?
How well perfused the tissue is
Binding of the drug to plasma proteins and tissue components
Permeability of tissue membranes to the drug
Ion trapping
P-glycoproteins
pKa
What are patient factors that affect drug distribution?
Oedema
Gender
Pregnancy
Ethnicity
Age
Dehydration
Health Status
What % of cardiac output goes to Kidneys?
22%
What % of cardiac output goes to the brain?
15%
How is blood flow distributed throughout the body?
More perfused organs receive more drug
What is Ion Trapping?
Basic drugs accumulate in acidic environments
Acidic drugs accumulate in basic environments
Drug becomes ionised in one compartment and is unable to cross membranes in it ionised form so it trapped
What is a compartment?
Sum of all those tissues into which a drug distributes at approximately the same rate
What are fast tissues?
Lots of blood and drug
What are slow tissues?
Less blood so drug takes longer to accumulate to concentration needed and so the reaction to the drug is slow/delayed
What happens in a single compartment?
All tissues are penetrated rapidly or not at all
Drug is assumed to spread instantly throughout all the space
Which organs are highly perfused?
Lungs
Kidneys
Liver
Brain
What is the perfusion of the lungs?
10ml/min/g
What is the perfusion of the kidneys?
4ml/min/g
What is the perfusion of the liver?
0.8ml/min/g
What is the perfusion of the brain?
0.5ml/min/g
What is the perfusion of fat?
0.03ml/min/g
What is the perfusion of muscle?
0.025ml/min/g
What is the perfusion of bone?
0.02ml/min/g
What organs are poorly perfused?
Fat, muscles and bone
How are compartments determined?
Blood and rapid tissues are the first compartment
Slow tissues are combined as the second compartment
What is the Volume of Distribution (Vd)?
Apparent Volume of distribution is the amount of fluid that would be required to contain the drug in the body at the same concentration as in the blood or plasma
Not a literal volume and should not be equated with a particular physiological space
Where can a drug be distributed to?
Plasma
Interstitial (extracellular) fluid
Intracellular fluid
What is Vd useful for?
Describing how well a drug is removed from the plasma and distributed to the tissues
What drugs will have small Vd?
Protein bound drugs that are trapped in plasma
What is the equation for Vd using drug strength and conc?
Vd = D/C
Where D = drug strength
C = Concentration of drug
Where is a drug with large Vd mainly found?
In the tissues and very little in the plasma
Where is a drug with medium Vd mainly found?
Similar drug conc in plasma and tissues
