Drug Absorption 🗸 Flashcards
Four fates if drug absorption in the body
absorption
distribution
metabolism
excretion
absorption
drug is absorbed from site of administration, entry into the plasma
distribution
drug leaves bloodstream and is distributed into interstital and intracellular fluids
metabolism
drug transformation by metabolism -liver and other tissues
excretion
drug and/drug metabolites excreted in urine, faeces or bile
6 modes of of drug movement across cell barriers
passive diffusion
facilitated diffusion
active transport
endocytosis
pH and ionisation
pH trapping
Passive diffusion
directly through lipid/aquaporins
drugs with high lipid solubility have a high concentration gradient
facilitated diffusion
done via specialised carrier proteins and doesn’t require energy.
movement is down a concentration gradient
water-soluble drugs can use this as they wouldn’t be able to cross the barrier without a carrier
cam show saturation kinetics - limited amount of carriers
active transport
done via specialised carrier proteins, requires energy
can move molecules against concentration gradient
moves water soluble drugs and can show saturation kinetics
Endocytosis
invagination of a part of the membrane
drug encased in small vesicle then released into the cell
transport of large drugs across cell membrane
pH and Ionisation
only unionised forms readily diffuse across the bilayer
degree of ionisation depends of pKa and local pH
Henderson-hasselbalch equation can determine proportions of drug in a given pH
pKa in ionisation
pH at which 50% of the drug is ionised and 50% is unionised
Henderson-hasselbalch equation in ionisation
the lower the pKa, the stronger the acid
allows you to determine how active a drug may be in the body
pH trapping
‘trap’ a particular dug based on its physiological property in compartments that have a particular pH
facilitates absorption at target
where do weak bases accumulate in pH trapping?
compartments with low pH (the reverse is also true)
