Distribution Flashcards
What are compartments?
diff locations in body where drug is distributed (referred to theoretically)
describe initial absorption & distribution of drug:
initial absorption into “central compartment” (systemic circulation) is followed by distribution to “peripheral compartments” (ex: liver, brain, other organs & tissues);
After absorption & entry into systemic circulation, there is…
… an immediate rapid distribution throughout body, esp to well perfused tissues
What are the 4 main factors influencing distribution?
- blood flow (perfusion) - depending on tissue, can range frm 3-30% of cardiac output
- drug physiochemical properties (lipid solubility, pKa, molecular size)
- binding of drug to plasma prots & cellular binding prots
- barriers to distribution
What is most abundant plasma protein?
Albumin; many drugs have varying affinities (weak interactions - hydrostatic interactions, van der waals, not covalent bonds)
The Free:bound equilibrium in blood plasma is due to?
reversible binding
What kind of drug can diffuse out of bloodstream and into tissues & why?
Free drug only; b/c plasma proteins are huge & cannot cross capillary walls
explain the dynamic nature of free drug diffusing from blood into tissues:
as free drug diffuses from blood to tissue, more is released from plasma prots until tissue sites become saturated. also, as free drug is excreted, more is released from plasma prots
What is albumin?
The bus; has many sites where interactions w/ chemicals/drugs can occur
What is tissue (cellular) protein binding like in adipose tissue?
It’s an important storage depot for highly lipophilic drugs (& persistent organic pollutants)
What is tissue (cellular) protein binding like in the liver & kidney?
they have high binding capacity for certain drugs
What is tissue (cellular) protein binding like in bone?
bone binds certain drugs (ex: tetracyclines) & heavy metals (ex: lead)
Consider tissue (cellular) protein binding in lean vs obese individuals:
Might need to give more drug in obese animals if it is lipophilic drug that accumulates in fat
Consider tissue (cellular) protein binding in lactating individuals:
breast milk is high in fat & can accumulate lipophilic drugs where they can become route of exposure for neonate (but route of excretion for mom)
What are some barriers to drug distribution?
BBB & placental “barrier”