2007 Second Sitting Paper 1 Question 12

2007-2-12 The binding of a drug (D) to its receptor (R) is described by the equation

D + R DR. Explain the following terms

a) The ratio of koff / kon

b) The implications for a low value for the ratio

c) The term affinitiy

d) The clinical implications for a high value for affinitiy

e) Two physiological factors that affect the rate constant

a) The ratio of the koff / kon

- koff describes the rate constant for the reaction DR D + R

- kon describes the rate constant for the reaction D + R DR

- Rate constant is the rate at which a reaction will proceed in one direction if all other

parameters are equal

- The ratio of the two rate constants is the dissociation constant or kd,

The likelihood of the drug-receptor complex to dissociate into drug and

receptor

b) The implications for a low value for the ratio

- A low value of kd implies that the forward reaction of the drug binding to the

receptor (kon) is favoured over the reverse reaction of the drug and receptors

disassociating (koff)

- This may be due to high affinity between the drug and receptor

- Few molecules of drug are required to achieve a given level of receptor occupation

than a drug affecting the same receptor with a high kd

This drug is more potent

c) Affinity

- Affinity is the attraction between 2 molecules in forming a complex

- High affinity bonds have stronger inter-molecular bond

- It is inversely related to the kd

The higher the affinity, the lower the kd and vice versa

2007 Second Sitting Paper 1 Question 12

d) The clinical implications for a high value of affinity

- If a drug has high affinity for a receptor, it has a lower kd than a drug that has low

affinity for the same receptor

- Fewer molecules of the drug are required to achieve receptor occupancy of a certain

level

- The drug is more potent

e) Two physiological factors that affect the rate constant

- The rate constant is described by the Arrhenius equation

� = �������

Where

k = the rate constant

A = the pre-exponential factor for the specific reaction describing the frequency of

collisions in the correct orientation

Ea = the activation energy, the minimum energy required for the reaction to occur

R = Universal gas constant

T = Temperature in kelvin

As temperature increases the rate constant approaches A,

As the temperature decreases the rate constant approaches 0

Modifying the Arhenius Equation gives

� = ������

��

Where ΔG0 = Gibb’s Free Energy, the change in enthalpy and entropy at a given

temperature for the reaction

2007 Second Sitting Paper 1 Question 12

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