Distribution
movement of a drug from blood to target or a location in the body of action to another (sometimes irreversible)
exit, site of action
Before a drug can act, it must _____ the blood and enter the ______
Rate of Distribution
how fast the distribution occurs
Extravasation
drug transport out of systemic circulation
4.5-6 L
What is the blood volume on average?
Blood capillaries
extremely thin walls that allow for nutrients and gases to exchange
passive diffusion & blood pressure
Drug distribution is drive by what 2 things?
lipophilic & lipid soluble
What molecules are easiest absorbed by the tissues of the body?
Perfusion-limited tissue distribution
initial rate of drug distribution to various sites depends on blood flow to the tissue
First phase
rapid distribution to organs of high blood flow
brain, heart, liver, kidneys
What are some organs that partake in first phase distribution?
Second phase
slower distribution to muscle, most organs, skin, and fat which have moderate blood flow
Permeability-limited tissue distribution
drug distribution is limited by the slow diffusion of drug across
blood brain barrier, placenta
Which areas of the body have tightly-knit cell membranes?
False
Ionized drugs will be absorbed by the tissues and not remain in the plasma. T/F?
affects, half-life
Tissue distribution ___ the apparent volume of distribution, which in turn affects the ____ of drugs in the body.
Apparent Volume of Distribution
total amount of drug in the body to the plasma concentration at a given time
high Vd, higher dose
A drug with a ____ & leaves the plasma and enters the tissue will require a ____ of drug to achieve a given plasma concentration
True
Volume distribution cannot be less than plasma volume. T/F?
high hydrophilicity, small Vd
Drugs with ____ and high plasma protein binding tend to have ____
high lipophilicity, large Vd
Drugs with _____ and high tissue binding tend to have ______
Concentration gradient or partitioning, blood flow to target tissues, physiochemical properties of the drug molecules, binding to components in the blood and tissue
What are factors that determine the extent of distribution?
Albumin
binds drugs that are weak acids (most abundant)
Alph-acid glycoproteins
binds drugs that are weak bases
inactive
Protein-bound drugs are pharmacologically ______
lowers
Protein binding ___ effective concentration
less available free active drug
Greater binding =
less metabolization, elimination, & longer half-life
Greater binding results in what?
True
Reversible binding may serve as a storage depot to prolong action. T/F?
Free form
active, diffusible, available for biotransformation and excretion
Bound form
-inert, non-diffusible, not available for metabolism and excretion
-major reservoir for drugs
-co-administration effects of drugs can occur
-binding is reversible
Glipizide
Which drug has a high affinity for protein binding?
drug interactions, drug persists in body longer
What are some effects of high plasma protein binding?