measurements in pharmacology

Question 1

what is occupancy?

Answer 1

the proportion of receptors occupied

Question 2

how is occupancy calculated?

Answer 2

occupancy = number of receptors occupied/total number of receptors

Question 3

how can occupancy be measured?

Answer 3

via radioligand binding studies. specific binding = total bound - non specific binding

Question 4

what is the law of mass action?

Answer 4

rate of a reversible chemical reaction is proportional to the product of the concentration of reactants

Question 5

what is Kd? what is a high Kd indicative of?

Answer 5

Kd is dissociation constant. high Kd = low affinity

low Kd = high affinity

Question 6

why might response measurement not give a direct indication of occupancy?

Answer 6

as we are not measuring ligand binding directly but the consequences of binding via activation of second messengers

Question 7

when is a system said to have spare receptors?

Answer 7

if maximal response can be evoked when occupancy is low

Question 8

what information does EC50 provide?

Answer 8

the potency; higher the potency, lower the EC50 value

Question 9

what is a partial agonist?

Answer 9

when the response has a reduced Emax but the same EC50 value as other agonists

Question 10

what is meant by affinity?

Answer 10

the probability of a drug molecule binding to a free drug receptor at any given instant

Question 11

what is meant by intrinsic efficacy?

Answer 11

a measure of a single agonist-receptor complex’s ability to generate a response

Question 12

what is the efficacy of a full agonist?

Answer 12

1

Question 13

by what is the size of the response governed by?

Answer 13

total number of receptors and nature of receptor-response coupling

Question 14

what is chemical antagonism?

Answer 14

where two substances combine in solution so the effect of the active drug is lost

Question 15

what is pharmacokinetic antagonism?

Answer 15

can refer to a reduction in the drug that is absorbed, or a change in drug metabolism

Question 16

what is physiological antagonism?

Answer 16

where two drugs interact with opposing actions and cancel eachother out

Question 17

what is non-competitive antagonism?

Answer 17

blocks a step in the process between receptor activation and response

Question 18

what is competitive antagonism?

Answer 18

antagonist acts at the level of the receptor and competes with the agonist for occupancy of the receptor

Question 19

how is reversible competitive antagonism characterised?

Answer 19

shift of the concentration response to the right with no effect on the maximal response

Question 20

what is dose ratio?

Answer 20

how many more times agonist is needed in the presence of an antagonist

Question 21

how is dose ratio calculated?

Answer 21

concentration of agonist in the presence of an antagonist/concentration of agonist in the absence of antagonist

Question 22

how can dose ratio be utilised to determine a numerical value for affinity of antagonist for receptor?

Answer 22

pA2 value is given by -log10 of the concentration of antagonist which produces a DR = 2

Question 23

how can agonist potency be measured?

Answer 23

shild regression analysis. when log10(DR-1) = 0, pA2 is minus this value

Question 24

what is irreversible antagonism?

Answer 24

when the antagonism cannot be reversed by washing the tissue with a drug-free solution

Question 25

on what factors is pharmacokinetics dependent on? why?

Answer 25

1 - absorption
2- distribution 
3- metabolism 
4- excretion 
these factors determine the concentration and time course of drug distribution in the body

Question 26

what are the routes of drug absorption?

Answer 26

oral
sublingual 
rectal 
epithelial
inhalation 
injection

Question 27

what are the factors which affect drug absorption?

Answer 27

1 - site/method of administration
2 - molecular weight (affects rate of diffusion)
3 - lipid solubility
4 - pH and ionisation - only uncharged molecules can cross lipid bilayer
5- carrier mediated transport - active or facilitated

Question 28

what are the major body compartments for drug distribution?

Answer 28

1- extracellular fluid - plasma 4.5% bw, interstitial fluid 16%, lymph 1-2%
2- intracellular fluids 30-40%
3- transcellular fluid 2.5%
4- fat 20%

Question 29

what facilitates the blood-brain barrier?

Answer 29

tight junctions in the endothelial cells of blood cells

Question 30

what is meant by drug metabolism?

Answer 30

the enzymatic modification of drugs before excretion

Question 31

what happens in phase I and II of drug metabolism?

Answer 31

Phase I - chemical modifications in the form of oxidation, reduction or hydrolysis
Phase II - conjugation of functional groups

Question 32

through which mechanisms are drugs excreted?

Answer 32

renal excretion- (glomerular filtration 20%, active tubular secretion, slow reabsorption)
GI excretion
lung excretion

Question 33

describe the one compartment model

Answer 33

drug disappearance from plasma follows an exponential time course characterised by plasma half-life, which is proportional to volume of drug distribution, inversely proportional to rate of drug elimination

Question 34

how is the one compartment model applied to repeated doses or sustained delivery?

Answer 34

plasma concentration approaches a steady state value within 3-5 plasma half lives. this depends on the frequency of drug administration

Question 35

what is the method for a radioligand binding assay?

Answer 35

1- prepare cells or m membranes using detergent and centrifugation
2- add radiolabels to samples at different concentrations and equilibrate
4- when equilibrated, remove unbound drug by filtration
5- count the radioactivity of the filter

Question 36

give an example of a drug that is an irreversible antagonist

Answer 36

the alkylating drug dibenamine on histamine responses in the guinea pig ileum

Question 37

into which three parts is renal excretion of drugs separated into?

Answer 37

1- glomerular filtration (20% drugs removed this way)
2- active tubular secretion -pumped into filtrate and out into urine
3- slow reabsorption - things in glomerular filtrate reabsorped, drugs that are poorly lipid soluble are are excreted as they are slower to reabsorb

Question 38

what does it mean when drug clearance is not fit by a single exponential?

Answer 38

the presence of the two compartment model where drug is distributed into a second compartment