Pharmacokinetics Flashcards
what is Cmax? what is it determined by?
highest concentration achieved by the drug in plasma. deterred by amount and bioavailability of drug administered and relative rates fo absorption, distribution to tissues, and metabolism/elimination
what is Tmax
time at which the drug reaches its highest measured concentration in the plasma
what does the area under the concentration curve (AUC) measure
animals total exposure to drug
what is half life
length of time it takes for the concentration of drug in plasma to decrease by half
when dose is doubled, what happens to the duration of drug action
extended by one half-life
what is dose (mg/kg) determined by
minimum effective concentration and toxic concentration
what is dose interval (times per day) determined by
clearance and half life
if dosage interval is greater than 5 half lives, at what rate will the drug accumulate in the body
no drug will accumulate in the body
what is dose rate (dose of drug per unit time) determined by
dose and dose interval
when we reach steady state, what is the relationship between rate of elimination and dosing rate
rate of elimination = dosing rate (drug concentration is no longer changing)
you want to reach therapeutic concentration quickly but there is a long half life. how can you shorten the time until a clinical effect is seen
give a loading dose (equal to volume of distribution x desired drug concentration)
what is drug absorption
refers to movement of drug from its site of administration to the blood
when is absorption not considered to factor into the pharmacokinetics
when a drug is given IV
why are lipophilic drugs more readily absorbed
pass through hydrophobic lipid membrane more easily
what is a common generally safe route of administration for a drug that is affected by GI transit times? what are 3 factors influencing absorption of this route of administration?
oral; variable absorption between individuals, species, and fed/fasted status
what is bioavailability
percentage of a drug dose that reaches systemic circulation
what does it mean if there is a large difference between the oral and IV dose of a drug
poor bioavailability is likely
why are unionized drugs better at crossing lipid membranes than ionized drugs
more lipid soluble (like non-ionized in like)
what does relationship between pH of the environment and pKa of a drug determine
whether the drug is ionized or non-ionized in its environment, and therefore affects its absorption
what drug route of administration has a bioavailability of 100%
IV (intravenous)
name at least 3 factors that influence the speed of distribution
blood flow/organ perfusion; ability of the drug to bind to the specific tissue and to plasma proteins; extent of distribution; rate of dissuasion across membranes; active transport of the drug across membranes
what is Vd?
apparent volume of distribution: the theoretical volume that would be needed to maintain the total amount of administered drug at the initial concentration (C0) in plasma after IV administration (Or at Cmax after other forms of administration); represents degree of tissue distribution of drug
how is Vd calculated?
Vd (mL or L/kg) = dose (mg/kg) / C0 (mg/mL or mg/L)
what does a HIGH Vd value mean?
MORE distribution from the blood into the tissues, so significant intracellular penetration. a high Vd value DOES NOT indicate penetration into a specific site, only general tissue distribution.
what does a LOW Vd mean?
LESS distribution from blood into the tissues, so predominantly in ECF
ion trapping affects the apparent volume of distribution. what will each unit of pKa away from pH in a compartment result in?
a 10x change in concentration of the drug in that compartment
will a basic drug accumulate or be absorbed from an acidic environment
accumulate (this is a consequence of ion trapping)
will an acidic drug accumulate or be absorbed from an acidic environment
be absorbed. (this is a consequence of ion trapping)
Snickerdoodle has an infection. Her milk has a pH of 6.8 and her blood plasma has a pH of 7.4. You give her benzylpenicillin which has a pH of 2.7. Will the concentration of benzylpenicillin be greater in the milk or plasma?
plasma. (benzylpenicillin pKa < milk and plasma pH, so ionized form of benzylpenicillin will predominate in both milk and plasma. the plasma pH is further from the pKa of the drug, so the drug will be more ionized in the plasma, and more of the ionized drug will be in the plasma. the non-ionized drug will equilibrate between tissues, meaning that the total drug will be higher in the plasma.)
what is metabolism
biotransformation of drugs to facilitate elimination
how is metabolism generally achieved
by reactions that increase the polarity/water solubility of the drug
what is the main site of drug metabolism
liver
what are 3 important factors that influence metabolism
age (metabolic enzymes may not be fully functional in neonates), health (especially liver disease can reduce ability to metabolize drugs), species (species differences in ability to metabolize drugs; can’t extrapolate safe or effective doses between species)
main enzymes responsible for phase 1 drug metabolism
cytochrome P450 enzymes
briefly, what does phase 2 metabolism involve?
increase water solubility by conjugating drug to exogenous substrates (glucoronidation, sulphate conjugation, acetylation) and deactivate active metabolites
what are 3 types of conjugation in phase 2 metabolism
glucuronidation (transfer glucuronic acid to substrate), sulphate conjugation (transfer of sulphate to substrate), acetylation (transfer acetyl group to substrate). also glutathione conjugation and methylation, but these are less important
after phase 2 metabolism, large drug molecules are typically excreted in ______, while small drug molecules are typically excreted in ______
bile; urine
what is the most important organ of drug elimination
kidney (exception: large drug molecules are more likely to be eliminated via secretion from liver into bile)
what is distribution largely determined by? what system is most important for distribution?
blood flow; cardiovascular system
what is primary site of absorption of orally administered drugs
small intestine
what processes determine the rate of renal excretion?
filtration + secretion - reabsorption. (therefore drugs or diseases that affect renal function will alter the renal elimination of drugs)
what is total body clearance affected by
total body clearance = hepatic clearance + renal clearance + other clearance
