Drug–Receptor Affinity

1. The ratio of the k_off / k_on
   • k_off describes the rate constant for the reaction DR → D + R
   • k_on 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 k_d,
     • The likelihood of the drug-receptor complex to dissociate into drug and receptor
2. The implications for a low value for the ratio
   • A low value of k_d implies that the forward reaction of the drug binding to the receptor (k_on) is favoured over the reverse reaction of the drug and receptors disassociating (k_off)
   • 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 k_d
     • This drug is more potent
3. 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 k_d
     • The higher the affinity, the lower the k_d and vice versa
4. The clinical implications for a high value of affinity
   • If a drug has high affinity for a receptor, it has a lower k_d 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
5. 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

Gladwin 2016

Answer by Gladwin