Flashcards in Lecture 13 Deck (30)
What are the components of a drug diffusion study apparatus?
membrane separating the compartments
stirrer bars (on in each compartment)
tube where substance enters, and tube where substances leaves
What happens in the donor and receptor compartments over time?
the concentration of the sample will decrease in the donor compartment and increase in the receptor compartment by diffusion through the membrane until equilbrium is reached
how can the mass transfer process be maintained / hve the time extended to reach equilibrium?
we can apply sink conditions
what are sink conditions?
in many diffusion experiments this consist of continually removing and replacing the receptor compartment with fresh solvent to maintain its concentration at a low level.
What can steady diffusion across a think film be described by?
the first law of fick
What happens if you increase the membrane thickness?
the flux will decrease
Why are the receptor and donor concentrations measured instead of the actual concentration gradient?
measurement of the actual concentration gradient is very difficult to do
What doesn't C1 = donor concentration and C2 = receptor concentration?
the concentrations are related to each other by the equation K = C1/Cd = C2/Cr
what is K?
the partition coefficient of the diffusant between the membrane/solvent
what can change K?
under sink conditions, what does the receptor concentration equal approximately?
0 as you are constantly removing the substance to maintain a low level
What is the permeability coefficient?
related to flux by the equation J = PCd
How can permeability also be expressed?
Dm/dt = SPCd or M = SPCdt
where M is the amount of permeant in the receptor
S is the total area of the membrane
How can the permeability coefficient be measured?
we can graph the amount of permeant in the receptor vs. time
If S and Cd are known, the straight line of this graph can be used to calculate P.
P = slope/Cd x S
Why is the graph of amount of permeant in receptor vs. time a reaction of zero order?
there is no change in rate
What is lag time?
theoretically we should maintain a steady state under sink conditions however in reality there is a lag time
How can we get rid of the lag time?
as we are not interested in the lag time we can rewrite the time component of M = SPCdt to substract the lag time
How do we substract the lag time?
M = SPCd (t-tl)
where tl is the time required for a penetrant to establish a uniform concentration gradient within the membrane separating the donor from the receptor compartments
What can we calculate by plotting mass of penetrant vs. time?
lag time, diffusion coefficient, and permeability coefficient
what is a permeation study?
What is the basic structure of the mammalian skin?
What is osmosis?
Is the diffusion of a solvent through a semipermeable membrane (NOT solute)
Follows the laws of diffusion, where the concentration gradient is the driving force
What is dialysis
This is the separation process based on unequal rates of passage of solutes and the solvent through a semipermeable membrane
What is hemodialysis
process through which blood is filtered specifically to exclude certain small molecules like K+, urea while preserving larger molecules (proteins)
What is ultrafiltration
Process used to separate macromolecules using a membrane and involves applying hydraulic pressure
We use molecular weight cut-off membranes which are specific pore sized to allow substances of molecular weight lower than the pores to go through
What are the mechanisms of transport across biological membranes?
What is passive transport
simple diffusion through driven by concentration gradient on the two sides of the membrane
Usually for lipid soluble compounds like vitamins, small molecules such as water and CO2
They move from an area of high concenration to an area of low concentration either by diffusing directly across the membrane or through a protein channel which is usually embedded in the membrane
What is active transport?
where a carrier or membrane transporter is used to bind a drug and transport it across the membrane
Energy is required as the driving force as it can proceed against the concentration gradient
What is facilitated transport?
This process does not require energy.
However it does need a specific carrier.
Usually for very large drugs.
It again uses the concentration gradient as the driving force.