Pharmacokinetics Flashcards
pharmacokinetics
the discipline that describes the absorption, distribution, metabolism, and excretion of drugs
*how the body affects the drugs
criteria for getting a drug to work
- unbound and active form of drug has to bind to receptor
- usually, the drug gets to the receptor via the plasma
- usually, the concentration of the drug at the active site decreases over time
steady state serum level
serum concentration when the amount of drug going into the patient = amount going out of the patient
*must be continued dosing to acheive
loading dose
one-time dose to get to a therapeutic level quickly
*usually followed by smaller amounts of continued dose
volume of distribution - definition
THEORETICAL volume that the amount of drug administered would occupy (it it were uniformly distributed) to provide the same concentration as it currently is in the blood plasma
volume of distribution - equation
Vd = amount of drug in body / concentration
concentration =
amount / volume
what will INCREASE volume of distribution (Vd)
extensive binding and/or distribution to the TISSUES
what will DECREASE volume of distribution (Vd)
increased binding to SERUM proteins
clearance - definition
represents a volume of plasma from which the drug is eliminated per unit time (volume/time)
rate of elimination = ? (for a first order process)
rate of elim = clearance x concentration
clearance - equation (for a first order process)
clearance = Vd x Ke
*note - Ke is the elimination rate constant
zero-order elimination of a drug
a CONSTANT AMOUNT is eliminated over time, regardless of concentration
*ex = 1 mg is eliminated every hour
*linear plot
first-order elimination of a drug
a constant PROPORTION is eliminated over time
*amount eliminated decreases as concentration decreases
*ex = 20% is eliminated every hour
*logarithmic plot
*MOST drugs are first-order
half-life - definition
time required to decrease the amount of drug in the body by HALF
half-life - equation
half-life = (0.7 x Vd) / clearance
how many half lives does it take to achieve steady state
~5 half-lives for ANY DOSAGE CHANGE (starting or stopping drugs)
are loading doses affected by changes in elimination
NO (but maintenance doses do)
how can you decrease concentration variability when giving a drug
give the drug more frequently
how does albumin affect volume of distribution
albumin is a serum protein, and many medications bind to it, SO:
*LOW serum albumin means more drug going into the tissues (HIGHER Vd)
*HIGH serum albumin means more drug staying in the plasma (LOWER Vd)
routes of absorption (how drugs cross membranes)
- passive diffusion
- facilitated passive diffusion
- active transport
- pinocytosis (rarely)
benefits of absorption of drug in small intestine
*largest surface area for drug absorption
*membranes more permeable than those in stomach
bioavailability (f) - definition
fraction of unchanged drug reaching SYSTEMIC CIRCULATION following administration from any route
bioavailability (f) for IV administration
= 1 (100% bioavailability)
bioavailability (f) - equation
f = AUCoral / AUCiv
loading dose- equation, including bioavailability
= (concentration x Vd) / f
maintenance dose - equation, including bioavailability
= (concentration x clearance) / f
*note - concentration is the TARGET concentration
first pass metabolism
the fraction of drug lost in absorption due to metabolism in the gut wall and liver
what is the main goal of drug metabolism
make the compound easier to excrete (by making it more water-soluble)
phase I reactions of metabolism in the liver
introduce or unmask a functional group (-OH, -NH2, -SH) via oxidation, reduction, or hydrolysis
phase II reactions of metabolism in the liver
conjugation with glucuronic acid, sulfuric acid, acetic acid, or an amino acid to make a polar compound
what is the most important phase I enzyme system
cytochrome P450 (CYP-450)
cytochrome P450 interactions
- substrate
- inhibitor
- inducer
cytochrome P450 - substrates
drugs that are a substrate of a CYP enzyme are metabolized via this pathway
cytochrome P450 - inhibitor
drugs that inhibit a CYP enzyme DECREASE the metabolism of active medications for that enzyme
*increase the concentration of active drug (compared to what you would normally see)
cytochrome P450 - inducer
drugs that INDUCE CYP enzymes increase the metabolism of active medications that are substrates for that enzyme
*decrease the concentration of active drug (compared to what you would normally see)
drugs that INDUCE CYP450
rifampin
phenobarbitol
carbamazepine
phenytoin
drugs that INHIBIT CYP450 (“magic rack”)
macrolides
amiodarone
grapefruit juice
INH
cimetidine
ritonavir
acute alcohol
ciprofloxacin
ketoconazole
common substrates of CYP450
warfarin
phenytoin
oral contraceptives
pharmacogenetics
the effects of a SINGLE genetic marker
pharmacogenomics
the COLLECTIVE influence of variability across the genome to modulate an individual’s drug response profile
what is the principle organ for excretion of drugs
KIDNEYS (for water-soluble substances)
-involves filtration, secretion, and reabsorption
