Pharmacodynamics drug-receptor interactions

Finally, developmental differences in pharmacodynamics can be observed in the absence of age-associated changes in the dose versus plasma concentration relationship. Marshall and Kearns demonstrated developmental differences in the pharmacodynamics of cyclosporin. In this study, the IC50 for interleukin-2 (IL-2) expression observed in peripheral blood monocytes obtained from infants less than 12 months of age and exposed in vitro to cyclosporin was approximately 50% of the value observed for older children. In this particular example, the pharmacodynamic differences appeared not to be the consequence of developmental dependence on pharmacokinetics but rather, in the true drug-receptor interaction. 

Drug-receptor interactions Dose-response relationships Molecular models of receptors and signal transduction mechanisms Biotransformation Pharmacokinetics Pharmacodynamics... 

QSAR studies are not restricted to the optimization of biological activity at the pharmacodynamic phase. Since toxicity also arises from drug-receptor interactions, the QSAR... 

As stated in Chapter 10, when the drug—receptor interaction involves feedback, the system becomes more complex. Hence, we will first present modeling and associated mathematical analysis of two typical processes. This will be followed by several examples involving drug pharmacodynamics organized around pharmacotherapy with drugs affecting the endocrine, central nervous, and cardiovascular systems. 

Although the maximum-effect pharmacodynamic models are empirically based/ they do incorporate the concept of a maximum effect predicted by the drug-receptor interactions described earlier. The Hill equation/ which takes the same form as the equation describing drug effect as a function of receptor occupancy/ relates a continuous drug effect to the drug concentration at the effect site as shown ... 

Pharmacodynamic phase Quality of the drug-receptor interaction Nature and intensity of the biological response Maximal activity Maximal selectivity Minimal toxicity... 

The most important differences between enantiomers occur in drug receptor interactions. Indeed, Lehmann [34] has stated, the stereoselectivity displayed by pharmacological systems constitutes the best evidence that receptors exist and that they incorporate concrete molecular entities as integral components of their active-sites. In contrast to the pharmacokinetic properties of a pair of enantiomers (Sec. 4), differences in pharmacodynamic activity tend to be more marked, and eudismic ratios of 100 to 1000 are not uncommon. 

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