Pharmacokinetics Flashcards
What is pharmacokinetics?
study of HOW a drug moves through the body
what is pharmacodynamics?
study of a drugs EFFECT at its site of action
what is pharmacogenomics?
study of how our GENOME INFLUCENCES the drugs effect or kinetics in the body
what is the acronym for understanding the mechanisms of how a drug works?
ADME
what does the acronym ADME stand for?
absorption, distribution, metabolism, excretion
what is absorption influenced by the most?
method the drug was introduced to the body and how the drug distributes (IV most bioavailable, oral most common but not as high bioavailability)
what is the partition coefficient?
ratio of octanol/water that determines the hydrophobicity or hydrophilicity of the drug
what are some factors that effect absorption?
concentration of drug/route
regional blood flow
lipophilicity
Surface area/membrane thickness
**smaller non polar absorb best
what is the absorption trend for drugs that are passively absorbed?
the higher the concentration, the more lipid soluble, the lower molecular weight, larger SA, greater regional blood flow =
FASTER DIFFUSION
what is the trend for absorption of drugs that use active transport?
limited absorption because there are only so many receptors/trasporters (increasing dose does not increase concentration)
what are an example of an active transporter that can go against concentration gradient?
P-glycoprotein MDR-1 transporters
(remember these can take the drug that was brought in my one transporter and sent it right back out of the cell)
what is special about diffusion of drugs that use active transport?
these can go against the concentration gradient
if you want a drug to be able to cross the BBB what modification does it need?
needs to be very small and lipid soluble
why cant pregnant women use nicotine?
nicotine can cross the placenta and the fetal liver can not handle it causing harm to the baby
Aspirin has a pKa of 3.5, where will it absorb best?
stomach/early duodenum because that is the most acidic place
if you were to give a drug with a pKa of 13.6 absorb best?
distal small intestine but a drug with a pKa that high would be better to be taken a route other than oral because the stomach acid will mess with its pKa
what is ion trapping?
weak bases get protonated when they cross into the lumen so they can not cross back over, trapping them inside
if a patients urine is too basic how can you help the patient?
give them an acid (too acidic give base)
if a patient takes too much aspirin how can you help increase the clearance of the aspirin?
give them a base
what is bioavailability?
fraction of unchanged drug reaching systemic circulation following administration of any route
how does increasing the bioavailability of a drug shift the PO curve?
shift it up and to the left (to be closer to the IV one which is 100% bioavailable)
why cant ibuprofen be taken with warfarin?
IB will disrupt W binding to albumin which will enhance the anticoagulant effect (warfain is a blood thinner, if it cant thin the blood the patient will be at risk of clot, ib makes it so cant thin, dose if IB is waaaaay more then warfrin so it will bind more, if the warfin is loose could cause toxic effect)
what is the equation for volume of distribution?
amount of drug in body/plasma concentration
how does elimination change for drugs with high volume of distribution?
body needs longer time to eliminate the drug
how does elimination change for drugs with low volume of distribution?
elimination is faster
what are the three main determinants for Vd?
properties of drug
size of pt
diease state of pt
what are some properties of drugs with high Vd?
lipophilic, binds to fat, small molecular weight
what are some properties of drugs with a low Vd?
plasma protein bound, water soluble, large molecular weight
when you stop takng a drug what eliminates first, what is last and why is this important?
blood, brain, lean tissue, fat
important cause things that pool in fat will take longer to be eliminated so this can causes prolonged effect after administration of drug has stopped
if we know the Vd and the amount of drug given we can calculate…
plasma level of drug
what is the definition of bioavailability?
APPARENT volume that reveals how the drug will distribute in the body
what weight is Vd calculated for?
70kg or 150lb
very lipid soluble metabolites can do what?
enterohepatic recycling, allows drug to stay in circulation longer (ex diazepam, oral contraceptive, warfarin)
what is a phase I reaction?
adding polar things to make it more water soluble for favorable excretion (oxidation, reduction, hydrolysis)
what is a phase II reaction?
conjugation reactions that make the drug even more polar
do all drugs do phase one and two?
no some do both, just one, just two or neither
what is the P450 system?
enzymes in liver that make drugs more water soluble for excretion
does dose effect competition for drug metabolism?
yes, more dose will metabolize first
what are two other metabolism mechanisms that are non p450?
xanthine oxidase and alcohol dehydrogenase
what are inducers?
drugs or herbals that INCREASE the amount of SIP or P5450 action INCREASING the metabolic rate
what happens to plasma concentration of a drug when there is an inducer?
decreases (because the drug is being metabolized fast, this could be good or could be bad if you are trying to get to the therapeutic dose)
what is drug inhibitor?
decrease action of SIPS or P450, decrease the metabolism of the drug
what effect does inhibitor have on plasma concentration of the drug, what should be considered?
increases plasma concentration
potentially puts pt at risk of toxicity, drug dose must be considered
what type of drug (specifically) do you worry about most with inhibitors?
those with a low/narrow therapeutic window
what s biotransformation impacted by?
rate of blood flow to liver
rate of entry to liver (F)
P450 induction/inhibition
individual pt differences
diet/environmental factors
what is clearance?
volume of plasma from which a certain amount of drug is removed per unit time (ml/min or l/h)
what gives us the best indicator of clearance?
glomerular filtration rate (GFR)
normal 120 ml/min
less than 30 ml/min = renal failure
what do you to with a pt with renal failure?
start the dose much lower than you normally would
how do you solve for clearance rate?
rate of elim/plasma concentration
what is first order kinetics for elimination rate?
concentration of drug is PROPORTIONAL to elimination rate (half life is consistent)
what is zero order kinetics for drug elimination?
linear, concentration independent of elimination so you can increase the concentration and the drug will still clear at the same rate RISK TOXIXITY
what is half-life?
time it takes for 50% of drug to be metabolized (long half-life sticks around much longer than short that is why it is important to know)
