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C J Carr

Publications and source records attributed to C J Carr.

At least 37 records · Page 2Linked to original sources
PubMed1985

History of the synthesis and pharmacology of isosorbide dinitrate.

A major research program in the University of Maryland School of Medicine, Department of Pharmacology, in the 1930s was the preparation of a large number of sugar alcohols and their anhydrides as substitute carbohydrates for diabetic diets. As an outgrowth of this work, many of these polyols were converted to their nitrate esters and investigated for their vasodilating properties. The organic nitrates that were synthesized were examined for their potency, duration of action, and possible therapeutic use. It was demonstrated that, contrary to prior belief, the depressor and vasodilating action was exhibited by their own molecular structure and not through hydrolysis and reduction to nitrite. The search for the finer mechanism(s) of action on the vascular musculature showed that these nitrated polyols and their anhydrides inhibited arterial adenosine triphosphatase, although this enzyme inhibition did not correlate with pharmacologic activity. Today the mechanism of action of these drugs is not clearly understood at the cellular level. The 1,4:3,6-dianhydrosorbitol 2,5-dinitrate (isosorbide dinitrate) was synthesized, studied, and reported in 1940. It appeared to be a useful drug because blood levels of the unhydrolyzed ester were found to persist for long periods of time. Subsequent clinical studies in the 1960s demonstrated its prophylactic value in angina pectoris and its prolonged action as a therapeutic asset. In 1967 the mononitrate was shown to be formed in vivo when the dinitrate was administered orally and has been studied as the possible pharmacodynamically active moiety.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

The evaluation of the carcinogenicity of environmental substances.

A review of the current status of carcinogenicity assessment leads to a number of observations that raise specific questions about the conduct and techniques of these bioassays. An approach is suggested that avoids many of the scientific controversies associated with the use of excessively high doses that cause secondary toxicity, leading to a promoter-like effect. Recommendations are made to utilize toxicokinetic data that relate metabolic characteristics of a chemical to its potential carcinogenic effects.

Animals↗
PubMed1982

Food and drug interactions.

A significant contribution could be made to patient care if nutritional biochemists, basic and clinical toxicologists, and pharmacologists in the various fields were to mount the studies needed to understand the nature of food-drug interactions. If only a small fraction of the 120 billion dollars per year spent for food or the 10 billion dollars expended for drugs were allocated for research in this area, advances might be made for the health of the nation. Changes in man's diet produce marked effects on drug metabolism. We know that changing a customary diet to one high in protein and low in carbohydrate increases the rates of metabolism of antipyrine and theophylline, and shifting to an isocaloric diet of low protein-high carbohydrate slows the rates of metabolism of these drugs. Presumably, high-protein-low carbohydrate diets in man resemble the animal studies with high protein diets that show enhanced hepatic drug metabolism. However, numerous studies emphasize the considerable individual variability to changes in human diets; some people have dramatic changes, whereas others exhibit little or no response. Similar individuality has been found in the response to enzyme induction by smoking. Numerous foods and food ingredients affect drug metabolism in human beings and apparently follow the same patterns as found in experimental animal studies with changes in the levels of cytochrome P-450 dependent monooxygenases in the liver and intestine. These changes presumably exert some protective action against environmental carcinogens, cocarcinogens, or promoters. Dietary modifications are brought about by use of weight-reducing diets, vegetarian diets, hospitalization, or post-operative regimens. These diets are often continued for long periods of time and it is likely they result in changes in the metabolism by the body of subsequently administered drugs or exposure to environmental chemicals. Methods are needed to measure inter-individual and inter-group differences in metabolism of foreign compounds in order to accurately assess dietary influences on drug metabolism and vice versa. Epidemiologic studies of rigorously selected human populations, coupled with the newer sensitive chemical analytical methods, will provide the necessary data base for these investigations.

Animals↗
PubMed1970

Man and drugs.

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Amphetamine↗