Distribution Lecture Flashcards
What happens to a drug after it is absorbed?
Must be delivered and taken up into tissues in order to reach their receptor site
Must reach a key site for metabolism and elimination
Define drug distribution
ALL processes that make up REVERSIBLE transfer of “free drug” circulating in the body and other sites that may bind the drug
Drug distribution is usually?
Non-homogenous.. Tissues differ markedly in the rates and quantity of drugs that they take up and this can influence drug action (redistribution can occur later)
Restricted uptake?
Serves a protective function
Decreases drugs ability to treat a disease that resides behind those restricted sites
What factors affect drug distribution?
Blood flow to clearance organs or target organs
Organ size and volume available to contain a drug
Capillary bed surface area
Capillary permeability
Drug uptake and bind by competing tissues
Cellular influx/effluc systems
Plasma protein binding
Presence of disease in key organ/tissues
What organs have high rates of blood flow?
Lung, kidney, liver, and brain
What organs have low rates of blood flow?
Resting muscle, skin, bone and fat
Tissues with high blood flow rates generally have?
High capillaries and a high capillary surface area for movement of substances across the capillary membranes into the organ or tissue
What are perfusion or flow limited?
Compounds for which uptake is sufficiently rapid that transfer is limited by delivery and not by permeability
- Usually smaller, lipid-soluble compounds –> “high-extraction ratio” drugs
What is capillary permeability?
Most allow ready exchange of small, water-soluble, polar, or charged compounds that can cross blood vessels via water-filled intercellular channels between cells
– can take hours to days for equilibrium
How can free drugs be affected?
Binding to plasma proteins such as albumin
OR
Active transport back out of a tissue cell by energy-dependent transport pumps (efflux pumps)
Plasma protein binding causes?
Less free fraction drug available in the plasma for uptake by the tissue
Structural features of a drug greatly impact?
Passage of the drug to certain restricted or sanctuary areas of the body
What is the CSF Sink Effect?
Removes stuff from the brain that has been inappropriately placed there
What is DPC681?
Protease inhibitor
- Inhibits protease that is necessary for HIV to complete its life cycle
- High efficient substrate for P450 3A4
