Exam 2 Flashcards
for a specific drug following first order elimination kinetics, drug elimination rate (RE) is ________(constant/not constant)
not constant
for a specific drug following first order elimination kinetics, clearance (Cl) is _________(constant/not constant)
constant
for a specific drug following first order elimination kinetics, elimination rate constant (k) is __________ (constant/not constant)
constant
the volume of fluid cleared of drug per unit time
clearance (Cl)
target concentration of a drug, at this the administration rate (RA) is equal to elimination rate (RE) - drug in = drug out
steady state concentration (Css)
if dose increases, what happens to clearance?
no change
if dose increases, what happens to administration rate (RA)?
increases
if dose increases, what happens to elimination rate (RE) to compensate for increase in administration rate (RA)?
increase
glomerular filtration rate is proportional to what?
concentration of free drug
body weight, body surface area, edema, cardiac output, drug interactions, extraction ratio, genetics, liver function, plasma protein binding, renal function
factors that affect Cl
if clearance decreases, what happens to elimination rate (RE) initially?
decreases
if clearance decreases, what happens to concentration at steady state (Css)?
increases
if clearance decreases, what happens to rate elimination after Css increases?
increases to match RA
if a patient has renal insufficiency, what happens to clearance (and subsequently half life)?
decreases resulting in an increased half life
the sum total of all clearance processes in the body including renal (ke), hepatic (km), and lung (kl)
total clearance (ClT)
model in which you calculate the clearance through individual organs, clearance is the fraction of blood volume containing drug that flows through the organ and is eliminated per unit time, fraction of drug extracted by organ (ER)
physiologic model
does an ER value of less than 0.3 mean high or low efficacy of elimination?
low
does an ER value of greater than 0.7 mean high or low efficacy of elimination?
high
urinary pH is often used to ______(increase/decrease) the renal elimination of drugs following cases of acute toxicity, basic strategy is to _______ (increase/decrease) the tubular reabsorption of the drug by making the molecule more ionized and _________(increasing/decreasing) its ClR
increase, decrease, increasing
increasing urinary pH decreases reabsorption of _______(acidic/basic) drugs
acidic
decreasing urinary pH decreases reabsorption of __________ (acidic/basic) drugs
basic
is active secretion saturable or not saturable?
saturable
is glomerular filtration saturable or not saturable?
not saturable
excreted exclusively by glomerular filtration, indicator of renal function
creatinine
if a drug’s ClR (renal clearance) is less than ClCR (creatinine clearance), by what mechanism is the drug being renally cleared?
glomerular filtration and reabsorption
if a drug’s ClR (renal clearance) is greater than ClCR (creatinine clearance), by what mechanism is the drug being renally cleared?
glomerular filtration and active secretion
if a drug’s ClR (renal clearance) is equal to ClCR (creatinine clearance), by what mechanism is the drug being renally cleared?
glomerular filtration only
completely cleared by the kidneys via glomerular filtration, not reabsorbed or secreted
inulin
route of administration, physiochemical properties of the drug, type and design of dosage form, physiology of the absorption site
factors that affect drug absorption
surface area of the GIT (Crohn’s disease decreases surface area), stomach emptying rate, food, GI motility, muscle vascularity
factors affecting drug absorption through the GIT
the % or fraction of the administered drug dose of a drug that reaches systemic circulation, does not indicate rate of absorption, equals 1 for IV bolus or infusion
bioavailability (F)
determines the bioavailability of a drug given by an extravascular route by comparison with the same drug given via IV route
absolute bioavailability
used to assess bioequivalence between different brands of the same drug dosage product
relative bioavailability
______ indicates the extent of bioavailability (F) but is not the same as F
AUC
drug metabolism prior to drug reaching general circulation, reduces bioavailability, for oral drugs sites of this include the liver and small intestine
first pass metabolism
time delay in absorption after a single oral dose (physiology, enteric coating), point of intersection between residual and extrapolated lines
lag time (t0)
this happens with drugs with short elimination half life (large k), dosage forms with slow absorption rates (small ka)
flip-flop of k and ka (k is greater than ka when normally k is less than ka)
allows for precise control of drug concentration (avoid fluctuations for drugs with narrow therapeutic window), mixing of drugs with IV electrolytes and nutrients, direct control of duration of drug therapy, drug administered at slower rate for lower risk of ADRs (especially for drugs that slowly equilibrate with tissue and follow multi-compartment kinetics)
advantages of IV infusion
for one compartment model drugs, is the drug infusion zero or first order?
zero
for one compartment model drugs, is the drug elimination zero or first order?
first
what does R represent in IV infusion?
infusion rate (mL/min or mg/hr)
used to obtain target Css (concentration at steady state) as rapidly as possible
loading dose (DL)
distribution and equilibration of drug is required before steady state reached, time needed to reach Css depends entirely on distribution half life (t1/2a), loading dose (DL) required to rapidly achieve Css
two compartment model drugs
