The Effects Of Agonists And Cr Response Curves

Question 1

Drug effect:

Answer 1

Positive or negative effect- receptors
Magnitude of effects- amount of drugs and number of receptors
Type of effect- what the receptor does

Question 2

Agonists:

Answer 2

Drugs that interacts with the receptors and resulting in a complex that creates a response
Can alter the activity of a receptor (drug efficacy)
-can be positive which causes an increase in the receptor activity
-can be negative which causes a decrease in receptor activity

the size of responses changes with the proportion of receptors occupied by the organist, which can change with the concentration of the organist. The proportion of receptors occupied is known as occupancy.

Question 3

Occupancy:

Answer 3

Occupancy occupied= number of receptors/ total number of receptors

Question 4

Relationship between occupancy and concentration of a drug:

Answer 4

Explains the relationship between occupancy and agnostic concentration:
As the agonist concentration increases the occupancy increases sigmoidally (means occupancy increases fast to start with but slows down as most receptors start to become occupied)

Question 5

Free receptor + agonist

Answer 5

K1
Free receptor ——>Agonist R complex ——>Activatiion of
<——
K2

transduction ———> Response system

Question 6

Rates

Answer 6

Forward rate= k1 [free receptor][agonist]
Backward rate= k2 [agonist-R complex]
At equilibrium: Forward rate= backward rate

Question 7

K A

Answer 7

Ka= backward rate constant (k2)/ forward rate constant(k1)

As Ka increases the backward rate of a reaction increases
A drug with higher Ka has higher backward reaction and tend to form fewer complex at a particular concentration
As Ka increases, affinity decreases

Question 8

K1 (N total - Na)= k2 (Na)

Answer 8

Na= number of receptors occupied by agonist
N total= total number of receptors
N total- Na= number of free receptors
[A]= concentration against agonist

Question 9

Occupancy= [A]/ [A] +k A

Answer 9

Equation describes how occupancy varies with the concentration of the agonist
KA is an important constant and numerically equal to the concentration of drug at which HALF the receptors are occupied

Question 10

Different types of agonists

Answer 10

Full agonists- they bind and activate receptor , 100% efficacy at receptor e.g. isoproterenol (which mimics action of adrenaline at B adrenoreceptor) e.g morphine mimics the action of endorphins at N-oploid receptors in the CNS

Partial agonist- have only partial efficacy at the receptor compared to a full agonist e.g. buspirone ,aripirazole

Question 11

Measuring occupancy experimentally

Answer 11

It’s hard to measure how occupancy varies with agonist concentration so we measure how a biological response varies with agonist concentration e.g.contraction or relaxation of a muscle
This is done by plotting concentration response curves which allows us to see differences between agonists

Question 12

3 Factors that determine dose response curves

Answer 12

Potency (EC50)- measure of the concentration of a drug at which becomes effective. Referred to as [A] which is the ligand,agonist,drug or hormone that binds to the receptor and initiates the response the lower the [A]50 the lower the concentration of a drug required to produce 50% of max effect and the higher the potency

Efficacy (Emax)- it’s the maximum possible effect for the agonist. Below a certain concentration of A, the response becomes too low to measure but at higher concentrations it becomes appreciable and rises with the increasing A concentration until it reaches really high concentrations where it cannot be further increased by the increase of A concentration and a max response/effect is achieved which is Emax

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