Tolerance dispositional

Utilize rats, sheep, and/or cattle to study the disposition of selected xenobiotics such as 2,3,7,8-TCDD and protocols that might enhance tolerance... 

When repeated doses of a drug are given, tolerance to the drug may arise if it affects its own disposition or response. Enzyme activities can be enhanced, which leads to an increased capacity for metabolism (e.g. patients on chronic therapy with barbiturates metabolise the drugs more rapidly than patients who have not previously taken the drugs). Alternatively, the receptor sensitivity may be modified so that the effect of a particular concentration of a drug is reduced after chronic use (e.g. the sedative effects of benzodiazepines). 

Therapeutic Concentration. In plasma, usually in the range 0.05 to l.Opg/ml. During methadone maintenance treatment there are often considerable fluctuations in plasma concentrations from day to day, and there appears to be a decrease in concentration as dispositional tolerance develops. 

Air quality standards have to take into account the seasonal fluctuation of tolerance. The level below which no effect will be seen on Norway spruce under field conditions is, however, much lower than that found in this fumigation experiment. The observed differences between graftings and seedlings and between both progenies (see Fig. 2) require greater numbers of replication for verification and interpretation because environmental stress and genetic disposition have to be separated from each other. 

Chave JP, Munafo A, Chatton JY, Dayer P, Glauser MP, Biollaz J. Once-a-week azithromycin in AIDS patients tolerability, kinetics, and effects on zidovudine disposition. Antimicrob Agents Chemother 1992 36(5) 1013-18. 

Functional tolerance to nicotine s effects is acquired quickly. Dispositional tolerance to nicotine also seems to develop. 

Regular use of alcohol results in some dispositional tolerance (see Chapter 5 for our detailed discussion of tolerance). Therefore, the drinker must consume greater quantities of alcohol in order to maintain a certain BAC. Dispositional tolerance can be reversed with a peritrd of abstinence from alcohol. Functional tolerance has a greater practical influence than does dispositional tolerance in altering how alcohol affects a person with repeated use. Tolerance to alcohol may be both acute and protracted. 

Alcohol use leads to dispositional tolerance and, more important, to both acute and protracted functional tolerance. 

Dispositional tolerance An increase in the rate of metabolizing a drug as a result of its regular use (Chapter 5). 

Hunt CA, Jones RT (1980) Tolerance and disposition of tetrahydrocannabinol in man. J Pharmacol Exp Ther 215 35-44... 

Merodio M, Irache JM, Valamanesh F, Mirshahi M. Ocular disposition and tolerance of ganciclovir-loaded albumin nanoparticles after intravitreal injection in rats. Biomaterials 2002 23 1587-1594. 

The clinician should have an understanding of in vivo antimicrobial agent disposition in order to select the most appropriate therapy for a given infection and to help monitor for clinical or bacteri-ologic efficacy. Serum concentration monitoring is the most common method used to attempt to maximize efficacy and minimize toxicity of antimicrobials. Since most antimicrobials are well tolerated at their usual doses, only a select few agents (e.g., aminoglycosides, chloramphenicol, and vancomycin) are monitored routinely in the current clinical environment. There are a number of direct and indirect methods that are used to quantify the concentration of antimicrobial in an experimental sample. 

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