Test 1-Mass transfer Flashcards
What is mass transfer (definition)?
A net movement of mass from one location to another in response to applied driving forces
When and where in the human body does mass transfer happen?
Occurs across different types of cell membranes and under different physiological conditions
What studies is mass transfer important for?
Dosage form design
ADME
What does diffusion of a drug through biological membrane involve?
Diffusion
Partitioning
Permeation
What is the diffusion step?
The drug’s diffusion through the aqueous medium that bathes the membrane
What is the partitioning step?
Passage of the drug molecules form the aqueous medium of the GI fluids into the lipid bilayer of the membrane
What is the permeation step?
Diffusion of the drug through the membrane
What is drug permeation?
Drug transfer - molecular diffusion of the drug through relatively non porous media
What does drug permeation depend on?
Drug partitioning
The structural nature of biological membrane
The nature of diffusion layer (GI content)
What is drug partitioning?
The ability of the drug to distribute in a mixture of aqueous and lipid system
How is drug partitioning across biological membrane measured?
By using a mixture of octanol (nonpolar) and water (polar) to get Kd and then Lop P which represents the drugs lipophilicity
What does lipophilicity affect?
Aqueous solubility (decreases with an increasing Log P)
Permability (increases with increase in Log P)
How do most therapeutic agents exist?
As either weakly acidic or basic in nature
What does aqueous solubility of a drug depend on?
pKa or the dissociation constant
pH of the solution
TF: The ionized states of a drug exhibit greater aqueous solubility than un ionized states
True because the ionized states are polar
What does pH of the surrounding fluid affect for the drug?
Solubility
Dissolution
Permeation
What kind of drugs are predominantly present in their un-ionized forms in the GI fluid in the stomach and upper part of the duodenum?
Weakly acidic drugs because of the lower pH which aids in their permeation in these areas
What kind of drugs are poorly absorbed in the stomach?
Weakly basic drugs
They exist largely in the ionized states at the GI pH
Why is the lipophilic nature of drugs important?
Because the biological membranes are lipid barriers
What is the most common process for the passage of drugs through biological membranes?
Passive diffusion
What is passive diffusion?
When drugs diffuse across a cell membrane from a region of high concentration (GI fluid) to a region of low concentration (blood)
What is diffusion rate directly proportional to?
The gradient
TF: small particles pass the membranes much slower than large molecules
False
They diffuse faster
What is passive diffusion of drugs governed by?
Fick’s law of diffusion
Drug molecules bound to other structural materials do/dont participate in diffusion process?
Do not
What happens in transcellular transport?
Drugs diffuse through the matrix or core of the membrane
Transcellular transport is ______ across different tissue membranes.
Constant
What does transcellular transport depend on?
Lipophilicity, polarity and molecular weight of drug molecule
What happens during paracellular transport?
Drugs diffuse through the water filled gaps between adjacent cells
Paracellular transport ____ from tissue to tissue.
Vary
What does paracellular transport depend on?
Size of the junction and size of the drug molecules
What polar compounds cross the biological membrane faster than non polar compounds?
Ones that have specialized carrier and transporters
What is the best studied system of active transport?
ATPase proteins that are particularly important in maintaining concentration gradients of small ions in cells
What are transporters?
Proteins that reside on biological membranes and serve to facilitate the passage of chemicals into or out of a cell
What do transporters located on the intestinal membrane influence?
Drug absorption
What do transporters on the hepatocyte influence?
Metabolism
What do transporters on the renal tubular membrane influence?
Excretion
What is MRP?
Multi-Drug Resistance Proteins
What is BSEP?
Bile Salt export pump
What are the two broad classes of transporters?
Influx (uptake) transporters
Efflux transporters
What do influx transporters do?
Transport drugs into the tissue/cell
What type of transporter is MRP?
Efflux
What type of transporter is BSEP?
Efflux
What do efflux transporters do?
Transport drug out of the tissue/cell
What are OATPs and what type of transporters are they?
Organic anionic transport proteins
Influx
What type of transporter is p-glycoprotein?
Efflux
What is MDR1 and what type of transporter is it?
Multi drug resistance 1
Efflux
What is BCRP and what type of transporter is it?
Breast cancer receptor proteins
Efflux
What is pore transport?
The aqueous channels which exist in cell membranes to allow very small hydrophilic molecules such as urea, water and low molecular weight sugars to be transported into the cell
