Lecture 3 Distribution Concepts Flashcards
What are the properties of the drugs for it to permeate the membrane via passive transcellular pathway?
Unbound and unionized
4 membrane characteristics?
- Tight junctions (BBB and gastric epithelial cells) VS fenestrations (blood capillaries and renal glomerular membrane)
- Memb thickness (0.005um - few mm)
- Equilibrium reached when unbound drug conc is same in aq phases on both sides of membranes - movement continues but net flux is zero
- carrier-mediated transport (facilitated and active; saturation pt present)
Normally, when logP increases, BBB permeability increases (linear).
Why are there some drugs that have high logP but have low permeability to BBB?
Very large molecules
Efflux pumps
Normally, when logP increases, BBB permeability increases (linear).
Why are there some drugs that have low logP but have high permeability to BBB?
Very small MW molecules
Uptake transporters
What are the 2 types of carrier-mediated transport?
- Passive facilitated diffusion
2. Active transport
What does it mean for Passive facilitated diffusion to have equilibrating transporters?
Unbound drug conc equal at equilibrium; transport is maximum
What does it mean for Active transport to have concentrating transporters?
ATP dependent, influx and efflux transporters
2 considerations for permeability rate limitation
- membrane properties (tight junctions or fenestrations)
- size and polarity of drug molecules (charge, hydro/lipophilicity, etc.)
What is the total body water for a 70kg patient?
42L
What is the plasma water (intravascular) for a 70kg patient?
3L
What is the intracellular volume (cells) for a 70kg patient?
27L
What is the extracellular water for a 70kg patient?
15L
What is the definition of apparent volume of distribution?
fluid volume in which a drug seems to be distributed to account for its plasma concentration.
What is the interstitial space (extravascular) for a 70kg patient?
12L
