L.3 Volume distribution Flashcards
Define volume of distribution (Vd) and apparent VD
The amount of drug that has been going through to tissues compared to how much stays in the systemic circulation.
The amount of drug in the body (from iv dose)/ concentration of drug in the plasma.
Apparent Vd: The volume that the drug must be dissolved in to give the concentration that is found in plasma.
What are the physico-chemical properties of drugs which increase rate of drug distribution throughout the body
Size (small), ionisation (non ionisation), lipophilicity (lipophillic), - increased ability to cross cell membranes
What are the physiological factors which influence Vd
- Body mass and composition- more space for drugs to distribute so Vd higher.
- Tissue blood flow- delivery of drug to tissues
- Tissue binding- more accumulation in tissues increase Vd
- Plasma protein binding: retaining drugs in the plasma (too big can’t excrete easily). decrease Vd
- Physicochemical properties of the drug
- natural barriers (eg. blood brain) ability to pass barriers which increase Vd
Why is Vd not physiological - can be Apparent Vd
Vd can exceed the total body volume because
- Drugs can bind to tissues instead of being in the circulation
- Drugs can bind to plasma proteins (albumin) but it can’t distribute to tissues to have its effect so volume of distribution is low. If other drugs or disease effect binding then this usually doesn’t change unbound drug concentration due to increased elimination. (except for rare cases).
- Drugs can partitioning into tissues- lipophilic drugs in fat, drug absorption onto bone instead of active site
What is the time course of drug distribution for one / central compartment model
There is instantaneous distribution of the drug so drug reaches peak concentration immediately and then elimination with a constant clearance over time (straightish slope down)
What is the time course of drug distribution for two / blood to peripheral tissue compartment model
(measured from the first compartment)
Instantaneous distribution (peak conc) in the first beaker. Almost as quickly, there is biphasic decline in concentration where the drug distributes to the second compartment to reach equilibrium and there is elimination (slower) from the first beaker and then it comes back from the second to the first to be eliminated too.
In the peripheral beaker there is a slow rise and then slow fall
Why is Vd important
It helps to calculated loading dose bc higher Vd (more accumulation into the tissues) means longer time taken to reach steady state and time for all the drug to be eliminated.
What influences steady state concentration
Clearance of drug and rate of input. Not Vd. Vd influences the time taken to reach steady state conc/ all the drug to be eliminated
What is the loading dose and equation
The initial dose administered (iv bolus or oral) to achieve the target concentration in a short time. Loading dose (mg)= Vd x target concentration . Therefore it is dependent on Vd- Vd needs to be filled before it can reach target concentration.
