Distribution Flashcards
Define distribution.
-movement of drugs between plasma & cells/tissue
-reversible transfer of substance from one location to another within the body
CELLS/TISSUES:
1. Site of action (PD)
2. Site of storage (PK)
3. Site of metabolism (PK)
4. Site of excretion (PK)
*goal of therapy = drug present at site of action
>sufficient conc for specific time
*food animals = drug residue risk
Describe the routes of distribution.
-blood vessels
>tissue perfusion
>protein binding
-across biological membranes
Describe tissue perfusion.
*rate of tissue perfusion relative to mass affects distribution of drug to them
1. Highly perfused tissues (high distribution)
-brain, liver, kidney, gland, heart
2. Moderately perfused tissues
-muscle, skin
3. Poor perfused tissues
-bone, adipose tissue
Describe protein binding.
- In plasma
-albumin: acidic & neutral drugs (main transporter in blood)
-globulin: a1 glycoprotein - Free drugs: unbound
-part available for delivery to tissue
-metabolically active - Protein binding
-high protein binding -> low vol of distribution (stays in blood w no action)
-99% bound doesn’t equal 99% protein sites saturated
-only in closed system & saturated where binding site competition can occur
[% binding = bound/total x 100]
*binding is reversible! -> equilibrium
*variation of binding affinity based on conc of drugs
Describe routes of distribution across biological membranes.
-depend on site of action, multiple lipoidal membrane barriers crossed
-chemistry
>solubility
A) hydrosoluble: ionized, polar
B) liposolubles: cross membrane easier
>pH & ionization & ion trapping
-conc gradient
-pores, transport channels
>liver, kidney, BBB (difficult penetration & diffusion back to blood)
Describe the properties of the BBB.
-tight capillary endothelial junctions
-glial cells
-active transport mech for removal of organic acids or bases
>ex: p glycoprotein efflux pump
-constant flow of CSF into venous drainage
Describe redistribution.
-movement of drugs from tissue back to blood or other tissues
-movement of substance from high blood flow to med/low
Describe compartment models.
-compartment = tissue
>rate for which the rate of uptake & clearance of drug are similar
>models based on measurement of plasma conc in PK to determine PK parameters
Describe one compartment model.
-all tissues and organs which the drug penetrates behave as if they were in equilibrium w the blood
-plasma conc reflect as if drugs remain in blood
Describe the two compartment model.
-central & peripheral compartments
-drug distribute from central (blood) to peripheral (tissue)
Describe the three compartment model.
-central & peripheral (2)
-peripheral have diff affinity to the drug
Describe the rate of distribution.
-two compartment model
-log curve is biphasic with a (distribution) phase & B (elimination) phase
Describe the volume of distribution. (Vd)
-vol of fluid required to contain the amt of drug in the body at a conc equal to the plasma conc of the drug
-represents the extent of distribution of drugs
(Vd = amt of drug / plama conc)
-amount of drug in body depend on dose administered (IV VS extravascular)
>used to calc drug dose from targeted plasma conc
Describe the different Vd values.
- Vd < 1L/kg = low distribution
-drug confined to blood (central) - Vd = 1L/kg = moderate distribution
-drug penetrate some peripheral (tissue) - Vd > 1L/kg = lg distribution
-drug penetrate multiple peripheral
Describe the volume of distribution units.
