ADME 2 Flashcards
what are the two routes to absorption?
transcellular and paracellular
what percentage of cardiac output supplies the GI tract?
10%
what is paracellular absorption also known as?
connective absorption
what sizes do molecules have to be in order to pass through the paracellular route?
radius less than 4 armstrongs
which way does passive diffusion move through a conc gradient?
down a conc gradient
what’s a problem with injecting phenytoin?
crystallisation in muscle tissue due to difference in PH
what is the problem with taking phenytoin orally?
poor absorption from the stomach- bad at low ph
absorption is irregular
is passive diffusion specific or non-specific?
non-specific, anything lipid soluble(most drugs)
what is facilitated diffusion?
Movement of drug across a cell membrane via a specialised transport system embedded in the cell membrane
- occurs without energy
- no conc gradient
where does active transport get its energy from?
from the hydrolysis of ADP to ATP
what system provides 1/3 of the energy we use?
na+/k+ ATPase channel
controls signals through the brain and water flow in cells
for passive diffusion are the species usually charged or non-charged?
non-charged
what is a requirement of passive diffusion?
must be in solution
what kind of equilibrium does passive diffusion have?
dynamic
what are the 6 requirements for passive diffusion?
1-water solubility 2- lipid solubility 3-molecule must be unionised 4-Molecular size 5-Concentration at site of absorption 6-Surface area of site of absorption
what do ionised compounds form?
complexes with endogenous ions resulting in an neutral species overall
what is lipinski’s rule of 5?
- Not more than 5 hydrogen bond donors
- Not more than 10 hydrogen bond acceptors(nitrogen or oxygen atoms)
- A molecular weight under 500 daltons(amu)
- A partition coefficient (log P) less than 5
what is the ph partition hypothesis?
When pH on one side of a membrane differs from the pH on the other side, then if the drug is either an acid or a base, the drug will be ionised to different extents on each side of the membrane
what happens in sink conditions?
Absorbed drug is removed by bloodstream•
Equilibrium is never established•
(High) concentration gradient is maintained
how much of a weak acid is ionised at ph=pka+2
99%
how much of a weak base is ionised at ph=pka+2
1%
what is the equation for the fraction of drug ionised?
1/1+antilog <10(ph-pka)