Pharmacodynamics: Receptor Theory

Question 1

what is pharmacodynamics

Answer 1

what a drug does to the body

Question 2

what is critical in determining drug actions

Answer 2

concentration of drug molecules

Question 3

what is Bmax

Answer 3

maximum binding capacity- information about receptor number

Question 4

what is kD

Answer 4

dissociation constant

• index of affinity lower value = higher affinity
• reciprocal of affinity

Question 5

what is the log of a number

Answer 5

the power which 10 has to be raised to to get that number

Question 6

what are ligand concentrations usually

Answer 6

less than a mole

Question 7

antagonists

Answer 7

bind to the receptor and simply block the binding of other ligands and do not cause the receptor to activate

they have affinity but no efficacy

Question 8

agonists

Answer 8

they have affinity and intrinsic efficacy as they can generate or stabilise an active form of the receptor

Question 9

what is efficacy

Answer 9

intrinsic efficacy and a response

Question 10

what is clinical efficacy

Answer 10

an indication of how well a treatment succeeds in achieving its aim

Question 11

what is a response

Answer 11

change in signalling pathway

change in cell or tissue behaviour

Question 12

what is EC 50

Answer 12

effective concentration giving 50% pf the maximal response

AKA potency

Question 13

what is concentration- drugs

Answer 13

known concentration of drug at site of action

Question 14

dose

Answer 14

concentration at site of action generally unknown

Question 15

where is the therapeutic target in asthma?

Answer 15

beta 2 adrenoceptors in the airways- they provide functional antagonism of contraction which causes relaxation of smoth muscle to relieve bronchospasm

Question 16

How do we achieve selectivity/ specificity?

Answer 16

drugs like salbutamol have different affinities at different beta adrenoceptors for example its affinity at the beta 2 adrenoceptor is higher than at the beta 1 adrenoceptor in the heart. There is a higher efficacy at the beta 2 adrenoceptor

Question 17

what determins ec50

Answer 17

affinity and efficacy

Question 18

which is variable and what is fixed

Answer 18

affinity and intrinsic efficacy- fixed

potency- varies e.g. no of receptors

Question 19

what are spare receptors

Answer 19

when an agonist induces a full respose without occuping all receptors the receptors that are left are spare receptors

when <100% occupancy = 100% response

Question 20

what is the purpose of spare receptors?

Answer 20

they increase sensitivity/ potency- allow responses at low concentrations of agonist

Question 21

what affects receptor number

Answer 21

tend to increase with low activity (up-regulation)
tend to decrease with high activity (down-regulation)
physiological, pathological or drug-induced changes

Question 22

What are partial agonists?

Answer 22

ligands or chemicals that evoke responses that lower the maximal response of a full agonist (i.e. they have a lower Emax values therefore lower intrinsic efficacy)

they have lower intrinsic activity and lower efficacy

Question 23

how are partial agonists relevant as drugs

Answer 23

can allow a more controlled response

work in the absence or low levels of endogenous ligands- but ca act as an antagonist if high levels of full agonist

Question 24

what is functional antagonism

Answer 24

antagonism of a cellular/tissue event being mediated by one mechanism by another mechanism

Question 25

what is an antagonist

Answer 25

antagonism of the action of an agonist at its receptor using a ligand

Question 26

reversible competitive antagonism

Answer 26

relies on a dynamic equilibrium between ligands and receptors- ligands can associate and dissociate

they outcompete the agonist and bind reversibly

cause a parallel shift to the right of agonist concentration-response curve
can be overcome

Question 27

what is IC50

Answer 27

gives an indication of antagonist affinity but influenced by [antagonist] and strength of stimulus

Question 28

irreversible competitive antagonism

Answer 28

when the antagonist dissociates slowly or not at all

with increased [antagonist] or increased time more receptors are blocked by antagonist- NON-SURMOUNTABLE

Causes a parallel shift to the right pf the agonist response curve and at higher concentrations supress the maximal response so Emax decreases

Question 29

non-competetive antagonism

Answer 29

bind at any site other than where the natural ligand binds

reduce orthosteric ligand affinity and/or efficacy