Lecture 7 Flashcards
What does ADME stand for?
Absorption, Distribution, Metabolism, Excretion
What are the mechanisms of the body which may stop the drug reaching and acting on its target? And what is one key way in which they are overcome?
Metabolism in the liver which may break down the compound, Biliary excretion, Renal excretion, binding and storage in tissues or being bound to plasma proteins
Use an enormous dose to help overcome body mechanisms
What are some key drug physiochemical properties for drug absorption?
Solubility in lipids or H2O which is important for absorption, distribution and excretion (most drugs have to balance water/fat solubility)
Chemical Structure which may have susceptibility to metabolism
What are the major organs involved in ADME?
GI tract (absorption), Liver (metabolism), Kidney (excretion), Lungs to a lesser extent for absorption and excretion of volatile anaesthetic gases
What are the four main mechanisms of transport across biological membranes?
Transcellular diffusion, Facilitated diffusion, active transport, endocytosis
What are the features of passive diffusion?
The most important mechanism of drug transport as most drugs are non-polar drugs and therefore lipid soluble
Concentration gradient is the driving force
No energy required
What are the features of facilitated diffusion?
For a few drugs movement occurs faster than predicted
Appears to depend on an oscillating carrier protein
Depends on concentration gradient
No energy required
Sugars and amino acids are the usual substrates so it is not as important for drugs but is sometimes used such as tetracyclines diffusion into bacteria
What are the features of active transport?
Can proceed against a concentration gradient but requires energy, can become saturated, can be organ specific
What does active transport allow?
Cells to accumulate compounds essential for growth, remove waste products, protect against toxins
What are the features of endocytosis?
Internalisation of a large molecule (MW>1000) such as Ig, hormones, cytokines, nanoparticles
What are the three steps involved in endocytosis?
Substrate binds to receptor
Invaginiation of receptor-substrate complex
Budding off and delivery of the vesicle into the cell
What are the features of filtration?
While most drugs have to cross through biological barriers, blood capillaries contain fenestrations that allows rapid interchange between blood and interstitial fluid
and glomerular capillaries which are extremely porous allowing all plasma constituents with the exception of macromolecules (MW>30,000) to pass through
