3 – Distribution Flashcards
Central compartment to peripheral compartments
- Initial absorption to systemic circulation followed by distribution to liver, brain, other organs and tissues
4 main factors influencing distribution
- Blood flow (perfusion): tissue dependent
- Drug physiochemical properties: lipid solubility, pKa, molecular size
- Binding of drug to plasma proteins and cellular binding proteins
- Barriers to distribution
- Binding of drug to plasma proteins and cellular binding proteins
a. Albumin is most abundant
b. Only FREE drug can diffuse out of bloodstream
i. As it diffuses (or is excreted), more is released from plasma proteins
- Barriers to distribution
-BBB
-placental barrier
BBB
-highly joined endothelial cells surrounding CNS and active transporter removal
i. *NOT fully developed in embryo and at birth (important toxicological implications)
Placental barrier
-ASSUME all drugs entering maternal circulation can cross the placenta unless proven otherwise
i. Drugs are tested extensively to see if they cause teratogenic effects to offspring
Tissue (cellular) protein binding: liver and kidney
-high binding capacity for certain drugs
Tissue (cellular) protein binding: adipose tissue
important storage for highly lipophilic drugs
o May need to give more drug to an obese animal
o Lactation: breast milk is high in fat and lipophilic drugs can accumulate
Route of excretion for the mother is the route of exposure to the neonate
Tissue (cellular) protein binding: bone
binds certain drugs and heavy metals
o Ex. lead mimics Ca2+
Volume of Distribution (VD)
- How widely a drug is distributed throughout the body
- “proportionality constant” used to compare distribution of drugs
- VD = total drug dose (mg) / plasma drug conc. (mg/L)
- HIGH: extensive distribution and high affinity for tissues
- LOW: restricted to blood plasma, mainly due to high plasma protein binding
