Pharmacodynamic pathways

Desensitization describes the rapid signal attenuation in response to stimulation of cells by receptor agonists. Changes in the coupling efficiency of receptors to signal transduction pathways and receptor internalization can account for desensitization and the development of pharmacodynamic tolerance. 

The pharmacodynamics and molecular biology of the possible pathways involved in the action of these pharmacological therapies have been extensively reviewed [24-28],... 

Fig. 15.4 Diagram showing the main pharma cokinetic and pharmacodynamic events mediated by the gene-protein network within the endothelial cells (EC), pericytes (P) and astrocytes (A). The intracellular cross-talk pathways that modulate the blood-brain bar-...

In this example, clarithromycin, a potent CYP3A inhibitor blocks the principal pathway of pimozide metabolism (CYP3A), and plasma concentrations of pimozide increase. A higher pimozide concentration (a pharmacokinetic effect) is associated with prolongation of QT c in EKG readings and potentially fatal torsades de pointes (via potassium channel blockade, a pharmacodynamic effect see Flockhart et al., 2000, May-hew et ah, 2000). As exemplified by this vignette, the... 

Olanzapine is metabolized by several pathways and is therefore unlikely to be affected by concurrent administration of other medications. Because olanzapine does not appear to inhibit any cytochrome P450 enzymes, it should not increase the availability of other medications through inhibition of such enzymes. Additive pharmacodynamic effects are expected if olanzapine is combined with medications that also have anticholinergic, antihistaminic, or aj-adrenergic side effects. 

Key Words pharmacogenetics pharmacogenomics pharmacokinetics pharmacodynamics polymorphisms candidate gene approaeh pathway analysis genomewide sean... 

Many of the pharmacodynamic interactions of most interest to the anaesthetist occur in pathways associated with the various divisions of the nervous system, central and autonomic, and thus influence the control of the cardiovascular system. 

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