Distribution Flashcards
what are the compartments for distribution?
plasma, extracellular interstitial fluid, intracellular fluid, transcellular fluid
which factors influence distribution?
- permeability across tissue barriers
- binding wishing compartments
- pH partition
- Fat:water partition
in our bodies drugs are in bound form or free form
bound form inactive – free form metabolised and extorted
equilibruim
how are the CNS and the brian protected from drugs/spread?
continuous layer of endothelial cells with tight junctions
how may the tight junctions in the endothelia be disrupted in the CNS?
inflammation
white blood cells and some small molecules can then pass
why will pass the BBB?
water, some lipid soluble molecules (small) and glucose
what size of molecules can pass through the BBB
smaller than 5000 dalton
why do the brain and muscle equilibrate quickly (if the substance crosses the BBB)
because they are highly vasularised
fat takes long time to equilibrate, why?
low vascularisation
what is the volume of distribution?
the theoretical volume that would be necessary to contain the total of administered drug (Q) at the same conc. that is observed in the plasma (Cp)
which factors that are related to the drug affect distribution?
Lipid solubility Molecular size Degree of ionisation Cellular binding Duration of action Therapeutic effects Toxic effects
which factors that are related to the body affect distribution?
Vascularity Transport mechanisms Blood/Placental barriers Free and bound forms of drugs Drug interaction Drug reservoirs Plasma binding proteins
protein + drug equilibrates with
protein drug compelx
plasma proteins can bind drugs to keep them in
an inactive form
in the plasma what does the protein albumin mainly bind to?
acidic and neutral drugs
in the plasma what does HSA normally bind to?
acidic and neutral drugs
in the plasma what does A1A normally bind to?
basic drugs
which drugs extensively bind to plasma proteins/
warren, statins, naproxen, diclophenac, naladixic acid
which drug barely bind to plasma proteins in the blood?
ahminoglycosides, fluconozole, codeine, lithium, ethanol
which are the major compartments of the body for distribution and what are their %?
- plasma (5%)
- interstitial fluid (16%)
- intracellular fluid (35%)
- transcellular fluid (2%)
- fat (20%)
define volume of distribution (Vd)
the volume of plasma that would contain the total body content of the drug at a concentration equal to that in the plasma
lipid in-soluble drugs are mainly confined to
the plasma and interstitial fluids, and do not enter the brain following acute dosing
lipid soluble drugs reach all (a) and may accumulate in (b)
a - compartments
b - fat
for drugs that accumulate outside the plasma compartments, Vd may
exceed total body volume
