pharmacology 3 - intro 3

Question 0

2 routes of elimination of a drug from the body?

Answer 0

1. biotransofrmation

2. excretion

Question 1

what are pharmacokinetics?

Answer 1

what body does to the drug

Question 2

excretion of a drug from where?

Answer 2

kidney 9renal) or biliary (gut)

Question 3

kidney excretion? water solubility? GFR? active transport from where?

Answer 3

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)

Question 4

where else can things be excreted from?

Answer 4

biliary, skin, pulmonary

Question 5

reabsorption from the kidney from urine?

Answer 5

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!!

Question 6

how do we quantify elimination? used to determine what? equation?

Answer 6

using T1/2. = 0.693/k (k is the slope gradient of the curve.)

this is used to determine dosing regimens.

Question 7

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?

Answer 7

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?

Question 8

what are the units of clearance? what is clearance? equation?

Answer 8

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

Question 9

how do we achieve a ‘steady state’ and what is it? after 7 half lives?

Answer 9

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%.

Question 10

3 ways to achieve staeady state? what would the graph look like?

Answer 10

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

Question 11

what are fisrt order kinetics as opposed to zero order?

Answer 11

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)

Question 12

what are pharmacodynamics?

Answer 12

what the drug does to the body!

Question 13

explain drug action? and drug effect?

Answer 13

drug action - interaction with the receptor

drug effect - subsequent chain of events caused by interaction with receptor.

Question 14

what is the drug receptor? eg?

Answer 14

anything the drug reacts with eg. muscarinic, enzyme, nucleic acid.

Question 15

what is a drug agonist? antagonist>

Answer 15

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)

Question 16

explain the terms - full/partial agonists?

Answer 16

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

Question 17

what is the DRC? what shape?

Answer 17

classic dose response curve (DRC) sigmoidal shape. response of tissue on y axis and conc of drug on the x axis.

Question 18

what is affinity?

Answer 18

tendancy to bind to a receptor

Question 19

what is efficacy?

Answer 19

how good at eliciting a response when bound eg. full/partial agonists.

Question 20

what is potency?

Answer 20

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.

Question 21

explain competitive or non-competitive antagonists? which reaches max efficacy stil? and how?

Answer 21

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!!

Question 22

drug plus receptor? equation? what is PA? equation? what is kd?

Answer 22

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)

Question 23

what happens to kd value if affinity is higher?

Answer 23

kd is reduced!! as less conc needed to occupy 50% receptors.