6 - Drug disposition Flashcards
What is drug disposition
Process whereby drug reversibly leaves blood stream and enters interstitium or cells
2 factors that make a drug easily cross a membrane
Hydrophobic
Lipophilic
Delivery from plasma to interstitium depends on (4)
Blood flow
Capillary permeability
Binding of drug to plasma & tissue proteins
Hydrophobicity
How does blood flow vary
Unequal cardiac output
What a slit junctions in capillaries for
They are large fenestrations that allow drugs to pass between blood and interstitium
What drugs do and don’t cross the blood brain barrier
Lipid soluble do pass through endothelial cells of capillaries in CNS
Ionised (polar) do not
Hydrophobic/hydrophilic - how to they cross membrane
Hydrophobic diffuse easily
Hydrophilic must go through slit junctions
Major drug binding protein
Plasma albumin
Are protein bound drugs active or inactive
Inactive - protein acts as drug reservoir
Equation regarding volume of distribution
Conc (steady state) - loading dose / Vd
3 components of water compartment in body
Plasma
Interstitial fluid
Intracellular fluid
Why would a drug be trapping in the plasma
Large MW or protein bound
Too big to move out of slit junctions
Vd = plasma water
Why would a drug be trapped in extra cellular fluid
Low MW, hydrophilic
Moves through slit junctions into interstitial
Unable to cross lupus membrane into intracellular
Vd = plasma + extra cellular
If a drug is in total body water …
It has low MW & hydrophobic
Moves through slit junctions and membranes into intracellular
Vd = plasma + extra cellular + intracellular
Is albumin bonding reversible
Yes
Loose bonds (not covalent)
