Pharmacokinetics (main slideshow - page 30 and up) Flashcards
where are drugs mostly metabolized
in the liver
what is the first phase of drug metabolism
modification that results in adding or exposing reactive groups to the drug
what is the second phase of drug metabolism
conjugation of the reactive group with a highly charged, water soluble substrate
what are some examples of reactive groups
-OH
-NH2
what is the result of drug metabolism
highly charged, sometimes inactive, mostly water soluble compound
many Phase 1 reactions of drug metabolism are catalyzed by members of what family
cytochrome P450
most drugs are metabolized by what cytochrome
CYP 3A4
where does CYP 3A4 exist?
liver and intestinal brush border membrane
what kind of drugs are ACTIVATED by metabolism
pro-drugs
what are 3 inducers of CYP activity
cigarette smoke
phenytoin
rifampin
what are 4 inhibitors of CYP activity
ketoconazole
erythromycin
grapefruit juice
THC
true or false: people can be genetically predisposed to have very high or very low CYP activity
True (for specific CYPs)
CYP inducers have what effect on therapeutic levels
decrease them (unless its a pro-drug, then they increase the levels)
CYP inhibitors have what effect on therapeutic levels
increases them due to accumulation of the drug (unless it’s a pro-drug, then the levels are decreased)
excretion of drugs occur mainly from what organ
the kidneys
although the kidneys are the main source of drug excretion, what other routes can they be excreted by
the GI tract
lungs
sweat glands
true or false: protein-bound drugs are filtered at the kidney
false, they are NOT
what kind of drugs are unlikely to be reabsorbed in the kidney
charged drugs
true or false: free drugs are filtered at the kidney
true
what is the elimination half-life
the time required to reduce the drug plasma concentration by 50%
true or false: half life is independent of the dose in most cases
true
after how many half lives is 100% of the drug assumed to be eliminated
4-5
what is Css
concentration at steady-state whereby absorption=elimination
(aka the levels of the drug stay steady)
if a drug is repeatedly administered before the previous dose is completely eliminated, what happens?
the drug levels accumulate with time
what does the time to steady-state depend solely on
elimination half life
when is steady state attained typically
after 4-5 half lives
what two things does the concentration level at Css depend on?
dose/dosage interval
bioavailability
in a continuous intravenous infusion, what would the dose/dosing interval be named
the infusion rate
what is the formula for the concentration level at steady-state
dose/ dosing interval*clearance
Css is proportional to:
F/CL
dose/dosage interval
bioavailability/clearance
what is a loading dose used for
to administer a higher initial dose to quickly reach a therapeutic concentration
what is the formula for a loading dose
Loading dose=Vd*target concentration
what are some physical processes that can cause pharmacological effects
changes in surface tension
lubrification
adsorption
what are some chemical processes that can cause pharmacological effects
neutralization
pH changes
changes in bodily fluids
what is affinity
force of attraction between receptor and drug
what is selectivity
degree to which a drug acts on a given target relative to other sites
what is agonism
when a drug has affinity for a receptor and binding to that receptor causes a pharmacological response
what is antagonism
when a drug has affinity for a receptor and binding to that receptor DOES NOT cause a pharmacological response
What 3 things does the dose-response curve determineq
min amount of drug to be used
max response a drug can elicit
how much to inc the dosage to produce the desired inc in response
what is the dose response curve
the relationship between size of an administered dose and the intensity of the response produced
what are the two properties of drugs that can be obtained from dose-response curves
efficacy
potency
what is potency
the amount of drug that must be given to elicit an effect
what is efficacy
the largest effect that a drug can produce
what is therapeutic drug monitoring
management of drug dosing regimen to keep drug levels within a normal rnage
