Flashcards in pharmacology 3 - intro 3 Deck (24):
what are pharmacokinetics?
what body does to the drug
2 routes of elimination of a drug from the body?
excretion of a drug from where?
kidney 9renal) or biliary (gut)
kidney excretion? water solubility? GFR? active transport from where?
water solubility plays a big part - polarity matters.
GFR - passive and depends on blood flow. depends also on size of molecule e.g if protein bound = too big.
active transport - PCT needs energy and against a concentration gradients - may become saturated also (limited)
where else can things be excreted from?
biliary, skin, pulmonary
reabsorption from the kidney from urine?
most particles can be reabsorped. depends on ionistaion degree again. if PH of urine can be manipulated to make more ionised in urine and so not reabsorbed and is excreted in urine. urine = alkaline!!
how do we quantify elimination? used to determine what? equation?
using T1/2. = 0.693/k (k is the slope gradient of the curve.)
this is used to determine dosing regimens.
what factors can affect the half life? (quantify elimination?) if kidney failure then what should happen to the half life and the dose given? what about a neonate?
1. access to sites of elimination
2. interaction with other drugs
3. physiological/pathological states (eg. kidney disease)/hepatic disease
4. renail failure - reduces clearance here. and t1/2 is increased, therefore the dose interval should be increased!
5. neonate with a greater VD? hey have more water volume in the body! - and ncreased half life since less drug presented to areas of excretion over time. so should again increase dose interval?
what are the units of clearance? what is clearance? equation?
c/b - volume of blood cleared of the drug by all elimination processes per unit time. ml/min.
t1/2 = 0.693 x vd/cb
how do we achieve a 'steady state' and what is it? after 7 half lives?
steady state is where levels of the drug remaine the same /stable from dose to dose. we achieve it by not assuming we have reached it until we have overcome 5 half lives - 95% or 7 half lives - 99%.
3 ways to achieve staeady state? what would the graph look like?
1. i/v CONTINOUS INFUSION
2. LOAD DOSE FOLLOWED BY REGULAR DOSE (FIXED)
3. FIXED INTERVAL OF REGULAR DOSE - TAKE 5-7 HALF LIVES TO REACH IT.
graph - t1/2 is the dose interval then will have 50% fluctuations around the steady state. - levels off after 5 half lives
what are fisrt order kinetics as opposed to zero order?
first order - high conc = higher elim rate (emilination rates changes with conc.)
zero - elim rate doesnt change and so may accumulate drug at higher concs. (unreliable half life)
what are pharmacodynamics?
what the drug does to the body!
explain drug action? and drug effect?
drug action - interaction with the receptor
drug effect - subsequent chain of events caused by interaction with receptor.
what is the drug receptor? eg?
anything the drug reacts with eg. muscarinic, enzyme, nucleic acid.
what is a drug agonist? antagonist>
agonist - drug thats binds and mimics the effect of the endogenous ligand (full/partial)
antagonist - drug that binds and has affinity but has no efficacy/intirnsic activity. it blocks the effect on the endogenous ligand /agonist by blocking the receptor site. (competitive,non)
explain the terms - full/partial agonists?
full - acheive maz response even if not all the receptors are accupied
partial - incapable of maz response even if all receptors are occupied. opioid - full
buperanoprhine - partial
what is the DRC? what shape?
classic dose response curve (DRC) sigmoidal shape. response of tissue on y axis and conc of drug on the x axis.
what is affinity?
tendancy to bind to a receptor
what is efficacy?
how good at eliciting a response when bound eg. full/partial agonists.
what is potency?
compare 2 drugs at different concentrations and see whic elicits more of a response at a certain concentrations. e.g durg on left of graph is more potent as it has max response at a lower concentration.
explain competitive or non-competitive antagonists? which reaches max efficacy stil? and how?
competitive - reversible as increaseing concenration of agonist can compete it off! not tightly bound. can still have max efficacy but need higher concentrations to reach it!!
non-competitive - irreversible (bad) as too tightly bound (covalent) eg. aspirin. would have to create more receptors in order to overcome the response. /enzyme. cant reach max efficacy!!
drug plus receptor? equation? what is PA? equation? what is kd?
R +L - R.L
more drug and more receptor means equation driven to the right!! more bound.
PA - occupancy of the % receptors occupied by the drug.
PA = CONC OF AGONIST/CONC+kd
kd - conc when 50% are occupied
nb - occupancy doesnt mean efficacy!!! (antagonists)