3 drug transfer- absorption Flashcards
A change in absorption leads to change in…
AUC, tmax, F (maybe t1/2 if absorption greatly prolonged)
A change in distribution leads to a change in…
t1/2, V,
A change in elimination leads to a change in…
AUC, Cl, t1/2,
possible mechanisms of absorptions of drugs
- pinocytosis (rare)
- filtration (glomerular): requires high hydrostatic pressure
- active transport - drugs structurally related to endogenous chemicals (tubular secretion)
- bulk flow of water- small water soluble drugs
- passive diffusion- most common mechanism
what does the rate and amount of passive diffusion depend on?
conc gradient, SA available for transfer, thickness membrane, a constant itself dependent on chemical characteristics of blood- molecular size and lipid solubility
rate of transfer and residence time at membrane
in which ionised form are drugs able to diffuse across a membrane?
in the uncharged form
what determines drug ionisation
for weak acid and bases, pKa = pH at which drug remains 50:50 charged: uncharged
what form would weak acids be at decreasing pH?
uncharged form
what form would weak bases be at decreasing ph?
charged form (BH+) accepted proton
give the characteristics of absorption for weak acids in the body
unlikely to enter BB (plasma has higher pH so exists in charged form)
absorption from stomach and intestine
charactersitics of absorption of weak bases in the body
likely to enter BB as exists in uncharged form in plasma
negligible absorption from stomach
good absorption from intestines
likely to be secreted in stomach and saliva
how does the presence of food effect drug absorption in the stomach, what type of drugs would be effected?
SA of stomach
increases time in stomach
- Acid stable drugs have slowed absorption
- Acid labile drugs stay longer and so more readily broken down- taken before food
- Some drugs: “Take before food”
- PPIs acid labile and so given in gastro- resistant capsules.
stomach has small SA
discuss the absorption of omeprazole (PPi)
capsule is a weak base- prevents breakdown by acid
capsule degrades at ph 5-6 in duodenum
acts systemically to inhibit PP in parietal cells so needs to be absorbed first
PPi is activated at acidic pH
drug absorption in small intestines
•Large surface area
- Major site of absorption
- Good blood flow
- Long residence time
- pH ~ 5.3
–Most weak acid and weak bases absorbed as high levels of uncharged drugs
define first pass metabolism
drugs absorbed from organs (eg. intestines) go ot liver via hepatic portal vein so may be metabolised before reaching systemic circulation
