Pharmacodynamics affinity

Pharmacogenetics the responses to dmgs may be significantiy different according to heritable factors that can modulate pharmacodynamic or pharmacogenetic factors (118). Atypical cholinesterase occurs in about 1 in 2000 Caucasians and is associated with a markedly reduced sensitivity to hydrolysis of the muscle-relaxant cholinesterase. Similarly, the reduced sensitivity to the anticoagulant warfarin is associated with a reduced receptor affinity. 

Of the many types of data plots that are used to help explain the pharmacodynamics of drugs, which plot is very useful for determining the total number of receptors and the affinity of a drug for those receptors in a tissue or membrane ... 

One frequently encounters the case where the equilibrium dissociation constant (iQ, see above) is defined by microconstants with Tast rates on and off the receptor. However, any change in potency in a chemical series (affinity) must represent an increase in the on (k+i) rate or a decrease in the off rate (fe i). Occasionally, either by accident or design, the off rate is altered dramatically enough to redefine the receptor kinetics of the compound such that the rates influence the actual pharmacodynam-... 

There was a direct relationship between the effect and the plasma concentration in the rat pharmacodynamic data and it was well described by a simple Emax model. Based on preclinical models for efficacy, a 90% effect was considered as the target for therapeutic effect. Finally the human C90 (human concentration corresponding to 90% effect, C90 man) was estimated by accounting for the different affinities and unbound fractions of each compound for the rat and human receptors as follows ... 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

Although the mechanisms of action for antisense oligodeoxynucleotide and 2 -MOE partially modified ASOs are the same, the 2 -MOE modifications provide increased affinity to the target mRNA while maintaining favorable RNase H activity and, therefore, enhanced potency and specificity over the first-generation ASOs [28, 40, 44, 45]. The pharmacodynamic section of this chapter will, once again, focus on 2 -MOE partially modified ASOs. 

Ariens, E., Affinity and intrinsic activity in the theory of competitive inhibition. I. Problems and theory, Archives Internationales de Pharmacodynamic et de Therapie, Vol. 99, No. 1, 1954, pp. 32-49. 

Structural differences of ARBs influence the variation in pharmacological (pharmacokinetic /pharmacodynamic) properties of these drugs. Affinity for the ATj receptor is highest with candesartan, followed by irbesartan, losartan, valsartan, and telmisartan. Differences and affinities at the ATj receptor are also involved in... 

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