Biological Barriers to Drug Absorption

Biological Barriers to Drug Absorption

• Drug absorption involves multiple steps from ingestion to reaching target cells
• The body has various barriers (epithelia and endothelia) that influence drug absorption
• Different types of epithelia and endothelia have varying permeabilities, impacting how easily a drug can pass through
• Simple squamous epithelium, like blood vessel linings, demonstrates excellent permeability
• Simple columnar epithelium, found in the stomach and intestines, exhibits very good permeability
• Stratified squamous non-keratinized epithelium in areas like the vagina and cornea has intermediate to very good permeability
• Stratified squamous keratinized epithelium, such as the skin, has poor permeability
• The absorption site thickness plays a key role; absorption sites are often single-layered.
• Regions needing strong barrier properties typically have multiple cell layers
• Capillaries, which carry drug molecules, exhibit varying permeability across different tissues
• Skin and muscle capillaries feature continuous endothelia with tight junctions, contributing to low permeability
• Capillaries in the intestines have sinusoidal endothelia with open fenestrae, enabling high permeability
• Liver capillaries boast fenestrated endothelia for substantial permeability

Transport Routes Across Epithelia

• Transcellular route: Drugs permeate the phospholipid bilayer, favoring higher lipid solubility and low molecular weight
• Paracellular route: Drugs pass through tight junctions between cells, influenced by tight junction permeability
• Transporters: Key proteins aiding drug absorption and influencing drug concentration
• Efflux transporters act to remove drugs, working against concentration gradients. P-Glycoprotein (P-gp) is a prominent example
• Influx transporters often assist related molecules, such as nutrients
• Some drugs can have similar structures to natural substrate molecules, improving their absorption.

Types of Transporters

• Uniport: Transports a single substance
• Symport: Transports multiple substances in the same direction
• Antiport: Transports substances in opposite directions.
• Active transport: Uses cellular energy, often against a concentration gradient
• Examples of active transporters are Na+/K+ ATPase, which facilitates essential cell processes
• Multiple families of transporters exist contributing to absorption of nutrients
• PEPT1 plays a crucial role in transporting di- and tri-peptides in the intestines

Cellular Uptake Mechanisms

• Pinocytosis: Cells engulf small fluid droplets using membrane vesicles.
• Receptor-mediated endocytosis: Cells take up specific substances using receptor ligands on cell surfaces, followed by vesicle formation and internalization.
• Phagocytosis involves engulfing larger particulate material through membrane deformation

Absorption Considerations

• Optimal log P values are important for efficient drug absorption in various locations like the cornea, nose, lungs, etc.
• Blood flow greatly affects drug distribution and absorption rates

Other Important Notes

• Grapefruit juice contains compounds that inhibit P-gp, impacting drug absorption

This quiz explores the complex interactions between various biological barriers affecting drug absorption in the body. Understand how different types of epithelia and endothelia influence drug permeability, and learn about the characteristics of these barriers in various regions of the body. Test your knowledge of permeability and absorption processes.