Pharmacodynamic barrier

Pharmaceutical barriers Insufficient chemical stability Poor solubility Inacceptable taste or odour Irritation or pain Pharmacokinetic barriers Insufficient oral absorption Marked presystemic metabolism Short duration of action Unfavorable distribution in the body Pharmacodynamic barriers Toxicity... 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

Pharmacodynamics Duration 1-4 weeks Absorption IM slow Time to peak serum levels 12-24 hours Duration 15-24 hours Absorption IM slow Distribution Poor blood-brain barrier penetration, enters breast milk Metabolism =30% hepatic inactivation Protein binding 65% Time to peak serum levels 1-4 hours Excretion Urine (60-90% as unchanged drug) Clearance Renal... 

Smith, B. J., Doran, A. C., Mclean, S., Tingley III, F. D., O Neil, C. A., Kajiji, S. M., P-glycoprotein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists, J. Pharmacol. Exp. Ther. 2001, 298, 1252-1259. 

The pharmacodynamics are affected due to altered levels of neurotransmitters and receptors in the central nervous system with age. The blood-brain barrier may be less effective, hence the brain may be exposed to higher drug and toxin levels in elderly subjects (Toornvliet et al. 2006). 

Changes in pharmacodynamics further complicate the pharmacology of many drugs in the neonate and infant. The blood-brain barrier is poorly developed, allowing more rapid transfer of drugs into the central nervous system (CNS). However, the response to higher brain concentrations may be tempered by an inadequate response due to lack of receptor maturation. 

The trials described so far have commonly shown a lack of usefulness of NKi receptor antagonists in the treatment of pain. But we do not know whether the failure of the selected compounds is a matter of pharmacodynamics (e.g. poor penetration of the blood brain barrier) or a genuine discrepancy between animal and human pain pathophysiology (Urban and Fox, 2000). Hence, animal tests should carefully be chosen whether they are predictive or not, and it would be helpful if a wider range of conditions could be examined (Hill, 2000a). Therefore, new preclinical analysis methods should be developed for a more effective judgement of likely clinical outcomes. 

This pharmacokinetic phase/pharmacodynamic phase model of dose-response can be described physiologically by considering each component of the phase as being separated by lipid membrane barriers that divide essentially aqueous environments. 

Describe the pharmacodynamic and pharmacokinetic barriers to effective plasmid-based gene delivery. 

Encephalopathy is a sign of advanced liver disease, either acute or chronic. It usually means that there is altered mechanics across the blood-brain barrier, probably increasing permeability and cerebral blood flow. As a result, patients are more susceptible to CNS side effects of drugs. There is also evidence that the pharmacodynamics, i.e. the receptor sensitivity, of drugs may be altered. 

The blocking action could also be implemented by administration of an enzyme or a catalytic antibody (regarded as an artificial enzyme) that not only binds but also accelerates cocaine metabolism and thereby frees itself for further binding [16-25]. Usually, a pharmacokinetic agent would not be expected to across the blood-brain barrier and thus would itself have no direct pharmacodynamic action, such as abuse liability [5]. 

The inherent pharmacologic properties of a drug determine its pharmacodynamic effects, and drug absorption, distribution, metabolism, and excretion are determined by the pharmacokinetic effects. The ease with which a drug passes into the systemic circulation and its ability to penetrate the blood-brain, blood-aqueous, or blood-retinal barriers determines the propensity to affect ocular tissues and functions. 

In the foregoing sections, pharmacon metabolism has been considered in relation to the pharmacodynamic, especially toxic aspects of action. Drug distribution also plays a role in the pharmacodynamic phase of drug action. Modulation of drug distribution, for instance, exclusion of penetration of particular barriers in the organism (e.g. the blood-brain barrier), or preferential bioactivation or bioinactivation in particular tissues, can modulate the spectrum of action of compounds and possibly exclude particular undesired effects. 

Distribution. Distribution is one of the important factors contributing to the duration of action of benzodiazepines. Benzodiazepines normally cross the blood-brain barrier quite easily and exert a pharmacodynamic... 

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