Mass Transfer Lecture 9/28/22 Flashcards
Define mass transfer?
Is a net movement of “mass” from one location to another in response to applied driving forces
What is ADME?
Absorption, distribution, metabolism, and excretion
What is dissolution?
Individual particles dissolved in the body
After undergoing dissolution, the drug is in gastrointestinal fluids in solution form ready to permeate biological membrane, leading to its (blank)?
Absorption
Diffusion step?
The drugs diffusion through the aqueous medium that bathes the membrane
Partitioning step?
Passage of the drug molecules from the aqueous medium of the gastrointestinal fluids into the lipid bilayer of the membrane
(Blank) is the molecular diffusion of the drug through relatively nonporous media
Drug permeation (transfer)
Drug permeation across the biological membrane primarily depends on:
- Drug partitioning
- The structural nature of biological membrane (both its biochemical compositions and its thickness)
- The nature of diffusion layer (the gastrointestinal content)
(Blank) is the ability of the drug to distribute in a mixture of aqueous (polar) and lipid (nonpolar) system.
Drug partitioning
If the drug is hydrophilic, the majority of the drug remains in what?
Water; but a trace of the drug is in the lipophilic part in order to maintain equilibrium
What is the distribution coefficient or partition coefficient of the drug, which is constant to a drug?
Kd
The logarithm of the partition coefficient (Log P) measures what
Lipophilicity (lipid solubility) of the drug
Lipophilicity is important physiochemical property of drug as it affects:
-aqueous solubility (polarity) decreases with increased Log P value
-permeability increases with increase in Log P value
Drug partitioning across biological membrane has been evaluated using the mixture of (blank) and (blank)
Octanol (representing the lipid, nonpolar system )
And
Water (representing the polar system)
Most therapeutic agents exist as either weakly (blank) or (blank) in nature
Acidic or basic
Aqueous solubility of a weekly acidic or basic drug, depends on the drugs (blank)
Dissociation constant (pKa) and the pH of the solution
The (blank) states of a drug exhibit greater aqueous solubility than the (blank) states
Ionized
Unionized
Mainly weekly acidic and basic drugs are subjected to ionization in the gastrointestinal tract. Therefore, there solubility dissolution and permeation are influenced by
The pH of the surrounding fluid
Basic drugs are dissolved Better in what kind of environment
Acidic environment
Acidic drugs are dissolved better in what kind of environment
Basic environment
Basic are absorbed better in what kind of environment
Basic environment
Acidic are absorbed better in what kind of environment
Acidic environment
Most weekly acidic drugs are predominantly present in what
In their unionized or nonpolar forms at lower acidic pH of the gastric fluid, which favors their permeation from the stomach, as well as from the upper part Duodenum of the intestine. But some very weekly acidic drugs who’s PKA values are greater than eight remain in an unionized form at all pH values Which favors their faster passage across biological membrane
Most weekly basic drugs are poly absorbed in the stomach because
They exist, largely in the ionized or polar states at pH 1-3. But weekly basic drugs with PKA values less than four remain Unionized through the intestine that favors there permeation
Review on biochemical composition of the membrane:
Polar heads and nonpolar tails
Biological membranes act as lipid barriers, and the lipophilic or nonpolar Nature of drug molecules is important.
Transfer mechanisms across membrane:
Passive diffusion (MW in range 100-400)
Pore transport (MW less than 100)
Carrier mediated
Ion pair transport (charged) (ionized)
Endocytosis (macromolecules)
What is the most common process for passage of drugs through biological membranes?
Passive diffusion
Passive diffusion is driven by the concentration gradient of
Drug across a membrane
Do drug molecules bound to other structural materials, such as proteins, tissues, participate in diffusion process ?
No
Governed by Ficks Law
When bound concentration decreases, unbound
Unbound is available for transfer now
Increase in thickness of membrane , (blank) absorption
Slower
(Note: all other parts of Ficks Law have a ( increase , increase in absorption relationship)
What is transcellular transport
Drugs diffuse through the matrix or core of the membrane. Constant across different tissues membranes. Depends on lipophilicity, polarity, and molecular weight of drug molecule.
What is paracellular transport?
Drugs diffuse through the water field gaps between adjacent cells. Very from tissue to tissue. Depends on size of the junction and size of drug molecule. (Has to be small in size to squeeze between cells)
Some polar compounds cross biological membrane faster than non-polar compounds through
Specialized carriers / transporters
What are the two carrier mediated transport systems?
Facilitated diffusion and active transport
What is facilitated diffusion?
It is less important, and is due to specific nature of this transport system, because drugs are specific to the body
What is active transport?
More important and goes against a concentration gradient and utilizes ATP and energy drives the movement
Transporters are proteins that reside on biological membranes and serve to facilitate the passage of chemicals into or out of a cell.
What are the two broad classes of transporters?
Influx, transporters, and efflux transporters
What are influx transporters?(uptake)
Transport drugs into the tissue or cell, and is most common. Organic anionic transport proteins are examples.
What are Efflux transporters?
Transport drugs out of the cell or tissue. P-glycoprotein and MDR1 are examples.
What is pore transport?
The aqueous channels which exist in cell membranes, allow very small, hydrophilic molecules, such as your rear water and low molecular weight sugars to be transported into the cells. However, because of the limited pore size, this pathway is of minor importance for drug absorption.
What are the two types of endocytosis?
Pinocytosis and phagocytosis
What is pinocytosis?
Cell drinking and occurs when dissolved solute are internalize through binding to nonspecific or specific membrane receptors
What is phagocytosis?
Cell eating, and occurs when a particulate matter is taken inside a cell
