absorption of molecules 2 Flashcards
meaning of bioavailability
the amount of drug that enters the systemic circulation and is accessible at the site of action
what is required for absorption
the drug to be in a solution
what must occur for a drug to be in a solution
dissolution
what factors affect the concentration drugs in solution in the GI
- complexation
- adsorption
- chemical stability
- micellar solubilisation
complexation in the GI
mucin which is present in the GI fluids forms complexes with some drugs and reduces absorption and bioavailability
what does complexation lead to
reduction in absorption as its no longer a single molecule
meaning of adsorption
becoming part of, sticking to the surface
what can the co-administarion of drugs and molecules containing solid absorbents cause
the adsorbents interfering with the adsorption of drugs from the GI tract
what causes reduced chemical stability
- stomach pH (acidic hydrolysis)
- enzyme degradation
does micellar solubilisation increase or decrease solubility in GIT
increase
what depends on the ability of bile salts to solubilise drugs
mainly the lipophilicity of the drug
what does a micelle have
a hydrophobic tail (hates water)
a hydrophilic head (loves water)
what are surfactants designed specifically for
their surface-activity, they are pharmacologically inert excipients
what is a common feature in many surfactants
a long non polar hydrocarbon chain
what does the non polar hydrocarbon chain do on a surfactant
it attempts to escape contact with water, this drives molecules to accumulate at interface
what happens once surfactants can’t stay at the top anymore
they are forced to enter the water and in order to satisfy interaction processes they self associate
what happens when the surfactants self associate
the hydrophilic heads interact with eachother and the hydrophobic tails interact with eachother
step 1 of drug absorption from GIT
partitioning of molecules between the GIT fluid (aqueous) and the GIT membrane (non aqueous)
step 2 of drug absorption from GIT
diffusion occurs across the membrane from high C to low C
low C is due to constant removal of drug into bloodstream
step 3 of drug absorption from GIT
partioning of molecules between the GIT membrane (non aqueous) and extracellular fluid (aqueous)
before entering the bloodstream
is it the ionised or non-ionised form the drug that partitions into the membrane
the non-ionised form
what depends on the extent of ionisation in the pH-partition hypothesis
the pH of the GIT fluid and the pKa of the drug
how does the amount of non-ionised drug influence extent of absorption
as only this portion of the drug is available to diffuse across the membrane
Ka meaning
the dissociation constant
what is Ka a measure of
how strong or weak an acid or base is relative to water
rule of two - ACIDS
if you go 2 pHs below it will be 0% ionised and if you go 2 pHs above it will be 100% ionised
rule of two - bases
if you go 2 pHs below it will be 100% ionised and if you go 2 pHs above it will be 0% ionised
pKa of carboxylic acid
4.5
pKa of R-OH
4-11
pKa of R-NH2
3.5
pKa of R-N
5
what is logD
the distribution coefficient
log is logD dependent on
pH
is logD greater or less than logP
less
what happens with drugs in the fed state
liquid and disintegrated tablets empty with food
controlled release retained for longer
what happens with drugs in the fasted state
little discrimination between formulation types
how do high carb meal impact pH
they have little change
how do high protein meal affect pH
elevates pH
how does liquid mixed meal impact pH
it elevates it but returns to base levels
what happens above pH 5 in stomach
pepsin is denatured and gastric acid production is reduced
