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TISSUE-LIPID SOLUBILITY AND "ADSORPTION" OF BARBITURATES

Date

1959-03

Journal Title

Journal ISSN

Volume Title

Publisher

ORCID

Type

Degree Level

Masters

Abstract

Since the barbiturates comprise one of the most widely used drug groups in modern therapy, their mode of action is of considerable interest and importance. None of the standard textbooks used in the teaching of pharmacology and related subjects, give s any reasonable explanation for the differences in rapidity of onset and duration of action of long- and short-acting barbiturates. The following statement as quoted from Jenkins and Hartung(1) is the standard treatment given to barbiturates. "The rapidity of onset and duration of action of the barbiturates depend in part on the structure and in part on the dosage, manner of administration, etc." This quotation is taken from the third edition (copyright 1949) and in the latest edition(2)(copyright 1957) they have modified their statement somewhat; that is, they have left the "etc." out. This stimulated the author to search further into the literature to see just what was known about barbiturates, particularly in regard to the mechanism of rapidity of onset and duration of action. Clinically, I was involved in the determination of blood barbit-urate levels and was therefore interested in recovery of barbiturates from serum . There is some discrepancy in the literature as to the degree of recovery using what appeared to be relatively similar methods of extraction.. Wright(3) and Walker(12) obtained only partial recovery, whereas Goldbaurn(4) approached complete recovery. My own experience using the procedure described later on was that of partial recovery. I thought this could possibly be due to "adsorption" to serum proteins as suggested by Maher(5), although Goldbaum(4) claimed the binding to be of a very weak n a t u r e z the complex being broken by contact with an organic solvent such as is used in the procedure. This prompted an investigation into extraction procedures and serum binding of barbiturates. During the course of my re ding I became interested in "adsorption" studies. All of the in vitro work was done on tissues of animal origin. Although drug reaction and metabolism are generally similar in humans, it was felt that some "adsorption" studies on human tissue would help complete the picture. Also, the "adsorption" studies had been carried out at relatively high barbiturate levels on rather dilute tissue preparations. Due to the development of slightly more sensitive methods(7) it was thought that studies using a more con-centrated tissue preparation and less barbiturate would be of value. It was not perfectly clear to me that metabolism was not a factor in some of the "adsorption" work done by Goldbaum. The latter portion of my thesis therefore involves the study of "adsorption" of a long-acting and a short-acting barbiturate to gray and white matter of human cerebrum, as well as to human liver. A brief study was done in regard to metabolism as a factor in "adsorption" to the above-mentioned tissues, during in vitro studies.

Description

Keywords

barbiturates

Citation

Degree

Master of Science (M.Sc.)

Department

Graduate Studies

Program

Advisor

Committee

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DOI

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