Distribution Flashcards
(26 cards)
What influences distribution physiologically
perfusion : blood flow
transportation: movement from vascular space
- transcellular : pass through cell
-paracellular : movement bw cells (large molecules)
Volume of Distribution
volume which drug appears to have been dissolved, reversible and dynamic process
- influences the conc of drugs in different areas, if the drug gets to SoA
depends on Q and properties of drug
What influence drug transport
drug permeability
membrane SE
conc gradient
What traits increase permeability
lipophilicity
unionized at pH 7.4
low MW
**biologics: are too large and therefore transport via paracellular + driven by osmotic pressure
What can limit rate of distribution
Either perfusion (Q) or permeability
** generally drugs are low MW, lipophilic and unionized so generally distribution is perfusion limited
Ex of Permeability limited distribution
Brain : high perfusion but limited by permeability
- only get super lipophilic drugs that aren’t substrate for PGP into brain through BBB
-BBB: less permeable, efflux pumps
What is PGP
p-glycoprotein: plays a role in limiting shit into the brain
- found in BBB and placenta, liver, kidney etc
T or F: V tells us the rate of distribution of the drug in the body
F - is tells us the tendency of the drug to stay in the plasma / measure of the extent of distribution
—- higher V :less in plasma
What is the minimum value for V
plasma v - 3L
- no max value
** can only measure V after IV admin
What does an increase in V do to t1/2 and K?
increase in V —- increase in t1/2 and decrease in K
** doesn’t tell us where the drug actually is
Changes to V impact on plasma time profile
increase in V —- decrease in k but increase in t1/2
—- steeper slope
—- decrease in Co ; intercept down
Difference in V bw hydrophilic and hydrophobic drug
hydrophilic: may have similar V to ECF
- decrease if dehydrated or if increase in renal or hepatic
—— change based on fluid status
hydrophobic drug: large V if obese
What are here normal HCT
M - 0.45
W- 0.4
T or F: blood volume is normal 7-8% of IBW
T - 5-6L
How to calculate amount of drug in plasma
Take BV as % of BW — 8% times weight
—- volume of blood
— Plasma volume = BV X (1-HCT)
——- this will give you plasma V
Amount in plasma = C of drug in plasma * V of plasma
How to get total amount of drug in body
Take V of distribution and * by weight === total V
Amount = V* C
Common drug traits that give small V
- large and can’t pass vascular walls (biologic)
- small + hydrophilic
- increase PPB— stuck in plasma
Traits that give large V
— increase degree of permeability (small, lipophilic, unionized)
- decrease PPB
- increase affinity to tissue proteins
T or F: total conc of drug in plasma is only equal to unbound c
F - equal to both added together
What is fu
unbound fraction (Cunbound/C total)
How does ultrafiltration work
way to measure PPB
- add plasma to device which has membrane with MW cutoff of 10kDa; only things smaller than this can pass through
- if drug PPB - it will be larger than 10kDA
—- only pass through is not PPB
- measure how much pass through vs what put in === degree of PPB
Albumin
- main PPB; bind to endogenous substrates
- can bind to acidic and basic drugs
80% of proteins in plasma but also found extravascular
- multiple binding sites for drugs
Alpha-1- acid glycoprotein
- only bind to B drugs
- smaller than albumin, acute phase reactant (increase in expression when stressed)
- single drug binding site
- less concentration of it in plasma
What can cause a decrease in albumin
renal disease, liver disease, surgery == decrease when stressed
—— decrease in albumin = increase in fu
