Henry W. Elliott

Effects of Acute and Chronic Administration of Narcotic Analgesics on Growth Hormone and Corticotrophin (ACTH) Secretion in Rats

Publisher Summary This chapter focuses on the experiments that are designed (1) to compare the acute effects of various narcotic analgesics on growth hormone (GH) and corticotrophin (ACTH)-secretion, and (2) to examine endocrine aspects of tolerance in rats treated chronically with morphine or methadone. The effects of narcotic analgesics on ACTH-secretion and on hypothalamo-pituitary systems have been reviewed recently. The effects of narcotic analgesics on GH and ACTH secretion in rats appear to be dose-related. The lower doses of morphine, methadone and codeine employed in this study mainly caused a rise of plasma GH and had little or no effect on plasma corticosterone. Higher doses of morphine and methadone produced increases of both plasma corticosterone and GH. Acute abstinence produced by naloxone resulted in a marked increase of plasma corticosterone and a diminution of plasma GH. Dose-response studies with narcotic antagonists showed that nalorphine produced simultaneous increases of plasma corticosterone and GH, while naloxone had no consistent effects on GH or ACTH secretion.

Central nervous system and cardiovascular effects of lorazepam in man.

A group of 15 healthy adult men was divided into three groups for a double‐blind study of the sedative‐hypnotic activity of single oral doses of lorazepam, a new member of the benzodiazepine series. Premedication procedures included complete blood counts, liver function tests, urinalyses, electroencephalograms, electrocardiograms and observations of central nervous system activity, as well as response to CO2, cardiac output, and peripheral vascular resistance. Three subfects received 100 mg. of sodium pentobarbital, 4 subfects received 2.5 mg., 4 subiects, 5.0 mg., and the remaining 4, 7.5 mg. of lorazepam. The same observations were repeated on all at intervals throughout the day of the test. There were no significant changes in laboratory findings or electrocardiograms and no severe impairment of respiratory and cardiovascular centers. The compound probably acts indirectly on vasomotor reflexes by way of the central nervous system. The serum concentrations of lorazepam reached a peak between 2 and 6 hours and then declined slowly. Clinical recovery occurred in 6 to 8 hours in all but one subject, even though serum levels were appreciable at 24 hours. About two thirds of the doses were recovered in urine as glucuronide within 96 hours.

Actions and metabolism of codeine (methylmorphine) administration by continuous intravenous infusion to humans.

Miosis produced by codeine is not antagonized by nalorphine until large oral doses are administered for several days. The present experiment was conducted in order to further study this characteristic of the codeine effect. Eight healthy male volunteers, who were former drug users, were divided into two groups. Subjects in the first group were given a continuous infusion of codeine, 30 mg/hr for 11-16 hr. No subjective effects were reported by the volunteers. In three of the individuals definite miosis antagonized by nalorphine was observed at 9.5 hr. The dose of codeine for the second group was 60 mg/hr for 11 hr. Mild but definite subjective effects were experienced by each of the participants in this group. Miosis appeared between 2 and 6 hr. Challenges at 4 and 6 hr were positive in two subjects and negative or equivocal in the other two. Codeine was excreted in the urine as free and conjugated codeine, morphine, and norcodeine. Maximum rates of excretion were similar for both groups, suggesting that the maximum amount of codeine that can be metabolized is equal or less than 30 mg/hr. Also codeine clearance, being greater than creatinine clearance, suggests that codeine might be excreted by glomerular filtration and tubular secretion. Blood levels of codeine in the 60 mg/hr group were about 10 times those reported as therapeutic. However, morphine or norcodeine were not detectable by the methods used.

Relationship of plasma meperidine levels to changes in anxiety and hostility

Abstract Six adult male former drug users were given single 100-mg doses of meperidine by the intramuscular route and an additional six were administered 100-mg doses by the oral route in a single-blind situation. Anxiety and hostility were measured by speech-content analysis before and after drug administration and correlated with plasma concentrations of meperidine. Significant decreases in anxiety and outward overt hostility scores occurred 1 to 1.5 hr postdrug when plasma meperidine concentrations were high, with return of these affect scores toward predrug values at 6 hr when plasma concentrations of meperidine were falling. Meperidine was found to resemble sedative-hypnotics in its effects on anxiety and hostility. Significant correlations were noted between plasma meperidine concentration and decrease in anxiety and hostility inward scores. The findings are consistent with the hypothesis that narcotic abuse is enhanced through the psychological effects of these drugs.

Content analysis of speech samples to determine effect of lorazepam on anxiety.

A study is described illustrating the me, in neuropsychpharmacologic studies, of an objective measure of psychological states, such as anxiety, through the content analysis of 5 minute samples of speech. In this report, the psychoactive drug tested was a new benzodiazepine, lorazepam. It was found to exert significant antianxiety effects (p <0.05) as measured by the content analysis method when administered parenterally at a dosage of 5.0 mg. compared to anxiety changes occurring after no drug or 3.0 mg. of lorazepam. Interesting physiological changes in relation to drug dose and anxiety inhibition were followed and are also reported.

Drug therapy of anxiety.

Sedatives have been used as antianxiety agents since the mid-1800s, when the action of the bromide ion on the central nervous system was recognized. Long-acting sedatives, such as phenobarbital and the benzodiazepines, currently are preferred because of their less intense, more constant effect and reduced risk of abuse as compared with the short-acting drugs.

A comparison of the effect of propylthiouracil on the respiration of thyroid slices from humans, chickens and rats

1. The QO2 of thyroid slices from hyperthyroid patients treated with propylthiouracil (PTU) was 140% that of slices from euthyroid patients. Similar results were obtained using thyroid slices from PTU fed and control chickens. 2. PTU feeding caused thyroid hyperplasia, increased QO2 more than could be accounted for by the hyperplasia but neither increased QO2 of muscle, cerebral cortex or spleen nor altered serum T4 levels. 3. PTU in drinking water increased the size and vascularity of thyroids from control but not hypophysectomized rats and had no effect on QO2. 4. The observations made on human, chicken and rat thryoid apparently reflect the effects of TSH rather than a direct action of PTU.