Theories of drug action

Question 1

what are endogenous mediators?

Answer 1

Chemical agent involved in the development of the inflammatory response

Question 2

state the main types of drug action [6]

Answer 2

1. agonists - activate receptors
2. antagonists - block receptors
3. ion channel interaction
4. enzyme activators
5. enzyme inhibitors
6. DNA interaction
7. inhibit transporters/pumps

Question 3

what is ventolin ?

Answer 3

chemical name is salbutamol

it is a β₂-adrenoreceptor agonist

Question 4

salbutamol leads to bronchodilation

explain the action of salbutamol

Answer 4

salbutamol binds to β₂ receptor, activating it

G protein changes shape , causing the GDP on the alpha subunit to be swapped for GTP

the alpha subunit simultaneously changes shape, transferring the GTP to the adenylyl cyclase

adenylyl cyclase is activated and uses ATP to form cAMP

cAMP leads to relaxation of airways via the action of protein kinases

Question 5

what are concentration response curves

describe their shape and its significant

Answer 5

x-axis = log con of agonist

y-axis = pharmacological response

sigmoidal curve = small change in conc results in significant change in drug response

Question 6

what is EC₅₀ ?

Answer 6

measure of drug potency

concentration of a compound where 50% of its maximal effect is observed.

the higher the EC₅₀ , the higher the conc required to result in a response

Question 7

what is eGFR?

Answer 7

estimated renal function ; tells you how to alter dose

Question 8

what is secondary prevention ?

Answer 8

prevents the event from occurring again

Question 9

name the 4 main superfamilies of receptors

also state the time needed for the response to come about

Answer 9

ligand gated ion channels (ms)

G protein coupled receptors (sec to mins)

catalytic receptors e.g receptor tyrosine kinases (min-hrs)

nuclear receptors (hr-days)

Question 10

where are β₂ and β₁ adrenoreceptors found?

Answer 10

β₂ found in lungs (2 lungs)

β₁ in heart (1 heart)

Question 11

what is affinity

Answer 11

ability of a drug to bind to its receptor

Question 12

what is efficacy?

Answer 12

ability of a drug once bound to activate the receptor via a conformational change

Question 13

what is the efficacy of antagonists?

Answer 13

zero

Question 14

what is the law of mass action

Answer 14

rates of binding/dissociation are proportional to conc

Question 15

what is the equation that gives you a measure of the affinity of a drug

Answer 15

given by its equilibrium dissociation constant

Question 16

what is K_D

Answer 16

conc of drugs needed to occupy 50% of receptors

Question 17

what is selectivity

Answer 17

preference of drug to binding to particular receptors

Question 18

What is the law of mass action

Answer 18

D + R ⇌ DR

forward rate = K_association[D][R]

backward rate = K_dissociation[DR]

at dynamic equilibrium, forward rate =backward rate so

K_{eqm dissociation} = [D][R] / [DR]

Question 19

What’s the difference between a full and partial agonist?

Answer 19

Partial agonists cannot activate the receptor to 100% of its capacity, full agonists can

Question 20

What are EC₅₀ and R_max values determined by?

Answer 20

affinity and efficacy

properties of the response caused by the drug

Question 21

How is the EC₅₀ and R_maxof an agonist affected by the presence of an antagonist

Answer 21

EC₅₀ is reduced but R_max remains the same

Question 22

Non-competitive antagonist drug action is non-surmountable

true or false?

Answer 22

True

Question 23

what is signal amplification?

Answer 23

max agonist response can occur without full occupancy of receptors

Question 24

How can you overcome the effect of a competitive antagonist ?

Answer 24

By increasing the conc of the agonist