ADME One Flashcards
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What are the physico-chemical properties of drugs?
- Solubility in lipids(non-polar-good) and water (ionized-good)
- Chemical structure
What is the solubility of a drug important for?In regards to ADME
Absorption, distribution and excretion
What is the chemical structure of a drug important for IN regards to ADME?
Susceptibility to metabolism
What are the major organs involved in absorption?
GI tract
WWhat are the major organs involved in metabolism?
Liver
What are the major organs involved in excretion?
kidney
What are the lungs important in with regards to ADME?
Absorption and excretion of volatile anesthetic gases
What does ADME affect?
Onset of drug action and duration + intensity of drug effect.
What sort of molecules are distributed faster?
Small, uncharged and lipid soluble drugs will distribute faster and more widely than bulky, ionized, water soluble drugs.
(most drugs most dissolve through the lipid bilayer and lipid soluble = nonpolar
What are the four main mechanisms of transport across the biological membranes?
Transcellular passive diffusion (90%)
Facilitated diffusion
Active transport
Endocytosis
What are the key features of Passive diffusion?
- Most important mechanism (90%) do this.
- Applies to non-polar drugs (i.e lipid soluble)
- Concentration gradient is the driving force
- No energy required
What are the key features of facilitated diffusion?
-Some drugs move faster than predicted, this appears to depend on an OSCILLATING carrier protein
- Depends on concentration gradient
- No energy required
- Sugars and AA are the usual substrates
(not so important for drugs)
i.e tetracyclines diffusion into bacteria
What are the specifics for active transport?
- Can proceed against a concentration gradient
- Requires energy (ATP)
- Can become saturated
- Specific organs i.e Liver, BBB, Kidney, Gut epithelium
What does active transport allow cells to do?
1) Accumulate compounds essential for growth
2) remove waste products
3) Protects against toxins
What are the principles of endocytosis?
Endocytosis = pinocytosis
- Internalization of large molecules and nano particles by cell
- Mainly for drugs with MW above 1000 i.e cytokines, hormones, growth factors etc
What are the three steps of endocytosis?
1) Substrate binds to receptors
2) Invagination of receptor-substrate complex
3) Budding off and delivery of vesicle into cell.
What is the last mechanism of drug movement?
Filtration
What are the important steps of filtration?
Most drugs pass through cells except in:
Blood capillaries - Contain fenestrations that allows rapid interchange between blood and interstitial fluid
Glomerular capillaries - Extremely porous allowing the passage of all plasma constituents except macromolecules MW 30k+
