how drugs work

Question 1

what is chemical signalling

Answer 1

the main mechanism by which biological function is controlled at all levels, from the single cell to the whole organism

Question 2

what is the function of receptors

Answer 2

chemical recognition

Question 3

what did Langley J.N 1905 do

Answer 3

he came up with the idea of ‘receptive substance’ to explain the actions of nicotine and curare on skeletal muscle

Question 4

what are drug targets

Answer 4

critical drug binding site

Question 5

what are the most drug targets

Answer 5

proteins

Question 6

exceptions of drug target

Answer 6

-any antimicrobial and antitumor drugs interact with DNA

–bisphosphonates used to treat osteoporosis bind Ca2+ salts

Question 7

what are the main types of regulatory proteins (4)

Answer 7

-receptors (classical signalling)
•ion channels
•enzymes
•carrier molecules (transporters)

Question 8

define the term receptor in pharmacology

Answer 8

it is used for protein molecule whose function is to recognise and respond to endogenous chemical signals

Question 9

what are the other molecules with which drugs interact with called

Answer 9

drug target

Question 10

how do receptors work (when agonist occurs)

Answer 10

• agonist activates receptor e.g. acetylcholine cytokine, steroid, growth factor receptors and then it can move directly through ion channel which closes/opens
• it can also go through a transduction mechanism which are three mechanisms:
• enzyme activation/ inhibition
• ion channel modulation
• DNA transcription

Question 11

what are the two types of ion channels and what do they do

Answer 11

• blocker- permeation blocker

- modulator- increased or decreased opening probability

Question 12

what did Hill A.V. 1909 do

Answer 12

he came up with the quantitative expression of the receptors

Question 13

what did Langmuir 1916 do

Answer 13

he independently derived the same equation as Hill which is why the equation is now known as Hill- Langmuir equation

Question 14

Clark A.J. 1926 experiment

Answer 14

• actions of acetylcholine and atropine on the frog’s isolated heart
• as the acetylcholine increases heart rate increases

Question 15

Gaddum J.H. 1926 experiment

Answer 15

-actions of adrenaline and ergotamine on the rabbit uterus

Question 16

what are inhibitors and where are they sat

Answer 16

sat on the active site and block the binding site

Question 17

what does B max mean

Answer 17

binding capacity

Question 18

what does K mean

Answer 18

equilibrium constant

Question 19

what does E max mean

Answer 19

maximum response

Question 20

describe transporter carrier molecule

Question 21

draw the binding curve

Answer 21

..

Question 22

describe the receptors in physiological systems and what do they do

Answer 22

-adrenaline (epinephrine) binds b-adrenoceptor in the heart (vascular smooth muscle)
•increase in force
•increase in heart rate

Question 23

what is non- uniform distribution of the drug

Answer 23

drug molecules must be bound to particular constituents (receptors) of cells and tissues in order to produce an effect

Question 24

what does pharmacological effects require

Answer 24

it requires non-uniform distribution of the drug

Question 25

agonist vs antagonist

Answer 25

- agonist activates receptor through signal transduction | - antagonist combines with the receptor without causing activation (no effect as the endogenous meditators are blocked)

Question 26

what is reciprocal

Answer 26

it is when individual classes of drugs bind only to certain targets and when individual targets recognise only certain classes of drug

Question 27

what will happen by increasing the dose of a drug

Answer 27

it will cause it to affect targets other than the principal one –can lead to side effects

Question 28

what is difference between agonist and antagonist regarding the efficacy and affinity

Answer 28

1) drug agonist bind to a receptor the affinity is K+1 and K-1 and then the efficacy is alpha and beta so therefore there is a response 2) dug antagonist bind to a receptor and has the same affinity however there is no efficacy as it is 0 therefore there is no response

Question 29

what does affinity mean

Answer 29

tendency of a drug to bind to a receptor

Question 30

what does efficacy mean

Answer 30

ability of a drug to activate the receptor–For antagonists, efficacy is zero (b = 0;

Question 31

partial vs full agonist

Answer 31

-partial agonists have intermediate efficacy, tissue response submaximal •Full agonists, efficacy is sufficient to elicit maximal tissue response

Question 32

what does a binding curve look like

Answer 32

...

Question 33

what does a logistic curve look like

Answer 33

....

Question 34

what does EC50 mean

Answer 34

concentration required to produce a 50% maximal response

Question 35

what does ED50 mean

Answer 35

dose required to produce a 50% maximal response

Question 36

what is a sigmoidal curve

Answer 36

when the mid portion of a curve is linear

Question 37

concentration-effect curve vs binding curve

Answer 37

concentration-effect curve cannot normally be used to measure affinity of a drug to a receptor •Response produced is not directly proportional to receptor occupancy

Question 38

where does a competitive antagonist bind too

Answer 38

it binds to the same site as an agonist

Question 39

what can happen if you raise agonist concentration

Answer 39

it can restore agonist occupancy

Question 40

explain dose ratio

Answer 40

ratio by which the agonist concentration has to be increased in the presence of antagonist to restore a given level of response

Question 41

difference between irreversible and reversible

Answer 41

...

Question 42

give an example of an irreversible enzyme inhibitor

Answer 42

aspirin (acetylsalicylic acid) •prolonged inhibition of platelet cyclooxygenase 1 (COX-1) and reduction of aggregation •irreversible acetylation of COX enzymes

Question 43

what does concentration effect demonstrate

Answer 43

relationship between drug concentration and the biological response

Question 44

what are the drug targets

Answer 44

receptors, Ion channels, enzymes, transporters

Question 45

what does partial agonist bring out

Answer 45

submaximal response

Question 46

what does inverse agonist reduce

Answer 46

the level of constitutive activation

Question 47

what does the two- state model take in account

Answer 47

constitutive activation