Pharmacokinetics Flashcards
is the protonated form of a weak acid ionized or non-ionized?
non-ionized
is the protonated form of a weak base ionized or non-ionized?
ionized
do ionized or non-ionized forms of molecules cross membranes more easily?
non-ionized
definition: pKa
pH at which 50% of drug is ionized and 50% is non-ionized
if the pH is less than the pKa of a drug, which form predominates?
protonated
if the pH is greater than the pKa of a drug, which form predominates?
unprotonated
are weak acids protonated or unprotonated in the low pH environment of the stomach?
protonated (non-ionized)
are weak bases protonated or unprotonated in the high pH environment of the intestines?
unprotonated (non-ionized)
what factors affect drug distribution?
- cardiovascular
- tissue binding
- molecule size
- lipid solubility
definition: phase I biotransformation
- generates more polar molecule by exposing functional group on parent compound
- readies compound for phase II
definition: phase II biotransformation
yields a more water soluble conjugated product to be excreted
what types of reactions occur under phase I biotransformation?
oxidative, reductive, hydrolytic
what types of reactions occur under phase II biotransformation?
- glucoronidation, sulfation, acetylation
2. glutathione conjugation, glycine conjugation, methylation, water conjugation
definition: first pass effect
- drug absorbed by the stomach or intestine will initially be carried to the liver by the portal vein
- orally administered drug will be exposed to metabolizing enzymes by the liver
- drug can be inactivated prior to reaching the intended target
what is the mechanism of drug elimination?
kidney
drug elimination in the kidney depends on what factors?
- GFR
- binding to plasma proteins
- alkalinization or acidification of urine
what are the two key parameters that impact drug dosage?
- volume of distribution
2. clearance
definition: volume of distribution
measure of the space in the body available to contain the drug (theoretical volume)
definition: clearance
- rate of elimination in relation to drug concentration
- expressed as mL/mg/kg
- helps determine capacity for drug removal by organs
equation: volume of distribution
V = amount of drug in body / concentration of drug in blood or plasma
regarding volume of distribution, how does a very large V impact drug distribution?
majority of the drug distributes to the extravascular compartment
regarding volume of distribution, how does a V that is smaller or closer to the actual blood or plasma volume impact drug distribution?
drug is retained primarily in the vasculature
equation: clearance
CL = rate of elimination / concentration of drug in blood or plasma
definition: zero order elimination
- specific amount of drug is eliminated over a period of time
- elimination process is at capacity or saturated
- independent of drug concentration
it doesn’t matter how much drug you give, you will only get rid of a certain amount because there are only so many enzymes - reduction is by a constant amount
what does zero order elimination look like on a time vs plasma concentration graph?
standard scale - negative linear
log scale - negative shoulder
definition: first order elimination
- not saturable
- clearance is constant over the range of drug concentrations in the body
can handle all the drug being delivered, and then some - will always eliminate a constant fraction of drug
what does first order elimination look like on a time vs plasma concentration graph?
standard scale - negative exponential (like half life)
log scale - negative linear
definition: capacity-limited elimination
point at which the concentration of the drug has saturated the elimination capacities of the system - mimics zero order kinetics
doesn’t matter if you’ve had 1 beer or 10 in an hour, you’ll always eliminate 1 beer per hour
definition: flow-dependent elimination
organ has high capacity or is NOT saturated by drug concentration - mimics first order kinetics
the greater the blood flow, the greater elimination
which drugs are eliminated in a capacity-limited fashion?
phenytoin, aspirin, alcohol
which drug is eliminated in a flow-dependent fashion?
propanolol
half life is dependent on what factors, if being eliminated by first order kinetics?
- volume of distribution
2. clearance
how can initial plasma concentration be determined in a one compartment system?
extrapolating the semi-log plot of plasma concentration vs time - requires low volume of distribution (one compartment system) and first order elimination
Cpo = dose / volume of distribution
what predicts the ratio of steady state concentration to dose seen following first dose?
accumulation factor
definition: accumulation factor
AF = 1 / fraction lost in one dosing interval
definition: bioavailability
the amount of drug that reaches the systemic circulation
what pharmacokinetic factors impact bioavailability?
- extraction ratio, clearance, hepatic blood flow
2. absorption, metabolism, distribution
how is bioavailability modeled graphically?
measure area under concentration of drug in blood vs time curve
what factors impact the area under the bioavailability curve?
rate and extent of absorption - dictate if drug will reach target concentration
what factor affects the extent to which a drug will reach circulation?
first pass metabolism / extraction ratio
definition: steady state concentration
point during dosing regimen when elimination of a drug is equal to bioavailability of drug - relationship between half life and steady state
the time a drug takes to reach steady state concentration is dependent only on which factor?
half life
what is required in order to administer a maintenance dose?
dosing rate (clearance x target concentration)
maintenance dose = dosing rate x dosing interval
