Lecture 6 Flashcards
Factors affecting membrane transport of chemicals
– Molecular weight/shape.
– Polarity.
– Membrane composition.
– Membrane thickness
Mechanisms of transport across membranes
– Simple diffusion.
– Filtration.
– Facilitated diffusion.
– Active transport.
– Endocytosis.
Simple Diffusion
- Transport proceeds in the direction of the concentration
gradient. - Transport is not saturable.
- No structural specificity.
- No energy requirement.
Partition Coefficient
Governs diffusion of uncharged drugs
Filtration
- Transport of xenobiotics due to bulk flow of fluid phase.
- Requires large pores within the membrane.
- Kidney is the best example.
Facilitated Transport
– Proceeds in the direction of the concentration
gradient.
– Has no energy requirement
Active Transport
– Can proceed against a concentration gradient.
– Requires energy.
Endocytosis
Two mechanisms:
– Phagocytosis (particulates).
– Pinocytosis (bulk liquid).
Dermal Route of Exposure
- Xenobiotic must cross several cell
layers to reach blood vessels and
be absorbed. - Factors:
– Lipid solubility.
– Ionization.
– Hydration of skin site.
– Thickness of skin site. - Specialized skin structures.
Inhalation Route of Exposure
- Gases, vapors, and aerosols.
- Rapid absorption from lung due to:
– Large surface area.
– Thin barrier.
– High rate of blood flow. - Breathing rate and blood flow are important.
Respiratory Excretion
– Exhalation of volatiles.
– Mucociliary clearance
GI/Liver Excretion
– Biliary excretion.
– Unabsorbed material.
– Direct excretion.
Urinary Excretion
Glomerular filtration.
– Tubular secretion
Other Excretion
– Milk.
– Sweat.
– Hair.
– Nails.
– Saliva
Prodrug
A pharmacologically inactive chemical entity that, when metabolized
or chemically transformed, is converted into a pharmacologically
active drug.
Inhalation Route of Exposure
Gases, vapors, and aerosols.
* Rapid absorption from lung due to:
– Large surface area.
– Thin barrier.
– High rate of blood flow.
* Breathing rate and blood flow are important
Drug Distribution Rate and extent depend on:
– Relative blood flow to tissues.
– Size, lipid solubility, and ionization
state of molecule.
– Plasma protein binding.
– Tissue protein binding.
– Specialized barriers
Drug Distribution Phases:
– Initial phase determined by blood flow.
– Later phases determined by tissue
affinity.
Drug Distribution Some tissues can store drugs:
– Fat (highly lipid soluble drugs).
– Bone (e.g., lead)
High solubility (in blood) substances
have “ventilation limited” excretion
Low solubility (in blood) substances
have “perfusion” limited excretion
Elimination of Particulates from the Lung
- Particles cleared via the “mucociliary
escalator”. - Particles also cleared via lymphatic drainage.
- Dissolved substances from particles are
removed via bloodstream or lymph.