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.
