Drug Aborption Flashcards
What are the factors that determine movement across the cell membrane?
- characteristics of the membrane.
- mechanisms of passage across membrane.
- dwell time of drug-membrane interface
- physicochemical characteristics of drug
- pH of microenvironment
- surface area
Where does most of drug absorption occur?
small intestine
Inner wall of small intestine is covered by numerous folds called plicae circulares
The surface of these folds contain villi and microvilli
Transcellular diffusion
The passive movement of drug through lipid membranes. This
movement is driven by concentration gradient.
95% of drugs are predominantly absorbed by passive transcellular diffusion
can be increased by removing ionized groups, increasing lipophilicity, reducing size
Paracellular diffusion
The passive movement of drug between cells via tight junctions.This movement is driven by concentration gradient.
Toxins and other insults may open tight junctions increasing permeability
Facilitated diffusion
A carrier-mediated process that involves a transport protein which moves drug with a concentration gradient.
Active transport
A carrier-mediated process that requires energy and can move drug against a concentration gradient.
Fick’s Law of Diffusion
dQ/dt= PC1
P= permeability constant
linear relationship
Gastrointestinal transit time
may be altered by food or drugs, can influence both the extent and rate of absorption
longer emptying of stomach, high 1/2 life, smaller concentration
shorter emptying of stomach, lower 1/2 life, higher concentration
Difference between passive and carrier-mediated diffusion
the latter is saturable and subject to competitive drug-drug interactions
slide 16 for graphs
Consequences of the Efflux transporter P-glycoprotein
- Limited drug absorption
- Enhanced drug elimination
- Limited distribution
Mechanism by which nanoparticles cross biological membranes
Endocytosis: Typically for large molecules
dependent of particle size
slide 21
