| How are drugs distributed in the body? | After drugs reach the blood (and minorly lymph), they should go to target organ/ tissues.
They circulate in a specific form (bound -usually to albumin or glycoproteins, or free)
They should get to the targets in a therapeutic concentration (enough to exert action) |
| What factors influence drug distribution? | Blood flow to tissue, capillary permeability, lipophilicity of the drug, degree of binding to the proteins
Usually muscles, viscera and fat get delivered drugs slowly while other organs have a higher rate of distribution like liver, brain, spleen...
There also should be equilibrium between drug in blood and target organ (bound drugs in blood compensate the drugs that go to interstitium) |
| How does blood flow influence drug distribution? | Blood flow varies among organs and tissues.
An example is propofol (anesthetic which is very lipophilic goes directly to the brain and crosses BBB easily, exerts action for 15 min since after it crosses barrier easily blood should equilibrate it so the drugs entering brain will go back to the blood and after this much time exert action on other tissues
Blood flow is also related to the organ mass so we should look at normalized blood flow (ml/kg/min |
| How does capillary permeability affect drug distribution? | Diff structural characteristics of capillary and drug nature determine drug distribution.
Brain: continuous capillaries, liver: fenestrated (drug enters passively or actively by transporters)
ex: levodopa has specific transporters in BBB
Cardiac muscles drugs entry is through endocytosis |
