4.17:
Quantitative Aspects of Drug-Receptor Interaction
The receptor occupancy theory states that the extent of a drug's response is related to the number of receptors it occupies.
A higher drug concentration leads to more occupied receptors, resulting in a higher response.
Drug–receptor complex formation is characterized by association and dissociation rates.
At equilibrium, the two rates are equal, and the ratio of their rate constants yields the equilibrium association constant Ka.
The inverse of Ka is the equilibrium dissociation constant Kd.
A higher Ka and a lower Kd value indicate greater drug affinity.
Fractional occupancy, calculated as the ratio of occupied receptors to total receptors and which is also expressed in terms of Kd, indicates the extent of binding at a given drug concentration.
Plotting fractional occupancy against the logarithmic scale of drug concentration shows that an increase in free drug concentration increases the fractional occupancy.
When the concentration equals Kd, the fractional occupancy reaches 0.5, indicating fifty percent receptor occupancy.
As the free drug concentration increases, the fractional occupancy approaches unity, resulting in a maximal response.
4.17:
Quantitative Aspects of Drug-Receptor Interaction
The receptor occupancy theory connects a drug's response to the number of occupied receptors. With higher drug concentrations, more receptors are occupied, leading to increased responses. The formation of drug-receptor complexes involves association and dissociation rates, which reach equilibrium when the forward and backward reactions are equal. The equilibrium association constant (Ka) and its inverse, the equilibrium dissociation constant (Kd), indicate drug affinity. Higher Ka and lower Kd values signify greater affinity, enabling more receptor binding even at low concentrations. Fractional occupancy, the ratio of occupied to total receptors, reveals the extent of binding at specific drug concentrations. When plotted against drug concentration on a logarithmic scale, fractional occupancy increases as free drug concentration rises, reaching 0.5 (50% receptor occupancy) when concentration equals Kd. As concentration continues to increase, fractional occupancy approaches unity, resulting in a maximal response.