a drug has been administered to a patient and absorbed into the circulation. the next step is distribution. what is distribution?
movement of the drug from the systemic circulation into tissues - to the target tissue, to the site of action of the drug
do drugs mainly leave the circulation through the arteries, veins, or capillaries?
what is the main barrier that drug molecules have to cross to leave the systemic circulation?
what type of cells are capillary walls composed of?
endothelial cells - simple squamous shape
how do lipophilic drugs leave capillaries?
diffuse through the cell membranes of the endothelial cells - the cells lining the capillaries. also through fenestrations
how do hydrophilic drugs leave capillaries?
through fenestrations or cross cell membranes by carrier proteins
what are fenestrations?
gaps between the endothelial cells lining capillaries
can plasma proteins (albumins and globulins) leave capillaries through fenestrations? why or why not?
no - they are too big
what are the 3 parts of the body that have extra barriers to drug molecules leaving the systemic circulation?
CNS - brain and spinal cord, eye, prostate
does the placenta present much of a barrier to most drug?
in general, you should assume that when you give a drug to a pregnant female, you are also drugging her fetus unless proven otherwise. true or false?
what is the blood-brain barrier (BBB)?
an anatomical arrangement of the lining of the capillaries in the brain. consists of 1) a lack of fenestrations in these capillaries and 2) an extra layer of glial (supportive tissue) cells between these capillaries and brain tissue
as a result of the blood-brain barrier, can very lipophilic drug molecules get into neurons?
as a result of the blood-brain barrier, can very hydrophilic drug molecules get into neurons?
can very tiny molecules, such as H20, O2, and CO2 get into neurons?
skeletal muscle, liver, kidney, and brain are all well-perfused tissues. are drugs distributed to these tissues quickly or slowly?
fat is poorly perfused tissue. are drugs distributed to fat quickly?
what is "redistribution" of a drug?
movement of drug from the blood, to the target tissue (brain), back to the blood, and then to a second tissue (fat)
what do we mean when we say that a drug is "protein-bound"?
individual molecules of the drug are temporarily "stuck" to individual molecules of plasma proteins in the blood by a chemical attraction.
do all drugs have the same degree of protein-binding?
can patient pH affect the degree to which a protein-bound drug is bound?
when a drug is protein-bound in the patient's circulatory system, does this mean that all of the drug molecules are bound?
no-some are bond and some are free, in a characteristic ratio for that drug
can individually protein-bound drug molecules diffuse of out of the circulatory system?
can individually protein-bound drug molecules be metabolized by the liver?
can individually protein-bound drug molecules be excreted by the kidneys?
do individually protein-bound drug molecules stay in the patient's circulation forever? if not, how do they get out?
no - individual molecules drift into and out of their bonds with plasma proteins. while they are free, they can diffuse into tissue, be metabolized or be excreted.
what effect does hypoproteinemia have on the activity of a drug that is normally protein-bound - will the drug show more activity in the patient or less?
if a hypoproteinemic patient needs a normall protein-bound drug, should the dose be increased or decreased?
what is "volume of distribution"?
an indictaion of the extent to which a drug is distributed throughout the patient's body
if you give a normal dose of a drug to a dehydrated animal, will blood levels of the drug be higher or lower than normal? how should the dose be adjusted?
blood level will be higher. dose should be lowered