J. Weldon Bellville

The respiratory and subjective effects of pentazocine

Pentazocine, a new potent analgesic, was studied to determine the respiratory depressant effects. It is a potent respiratory depressant whose dose‐effect curve slope is not significantly different from that of morphine. In respiratory depressant effect it is estimated that 21 mg. of pentazocine is equivalent to 10 mg. of morphine. However, the time‐effect curve for pentazocine appeared to be different from that of morphine for it achieved a higher initial peak effect and showed a more rapid decline.

Respiratory and subjective effects of d‐ and I‐pentazocine

The relative respiratory depressant potencies of the d‐ and l‐isomers of pentazocine were determined in a crossover study. The l‐isomer was found to be a potent respiratory depressant (13 mg. ≎ 10 mg. morphine). The response to 30 and 60 mg. of the d‐isomer did not differ significantly from placebo. The possibility that higher doses of d‐pentazocine might produce significant respiratory depression cannot be dismissed, however. Sub;ective effects similar to those produced by morphine were noted, although there appeared to be qualitative differences. Lightheaded and dreamy reactions were noted more frequently, for instance, after l‐pentazocine. Some effects, such as anxiety, were reported after d‐pentazocine while their opposites, stich as relaxation, were reported following administration of the l‐isomer.

On-line Computation of Cardiac Output from Dye Dilution Curves

An analog computer circuit for calculating cardiac output and mean transit time has been described which receives as its input the output of a cuvette densitometer. The results obtained with the computer have been compared with those obtained by the usual method.

Evaluating side effects of analgesics in a cooperative clinical study

Studies in large numbers of patients successfully identified incidence and severity of adverse effects of analgesic agents in patients with postoperative pain. In a series of studies, such data from 5 hospitals taking part in the Veterans Administration Cooperative Analgesic Study were pooled. The survey involved up to 1,000 patients receiving more than 2,000 medications in the comparison of a single drug with morphine. Statistical methodology and standardized training of nurse observers permitted pooling data from separate sources. For some side effects, it was possible to make relative potency estimates. The approach used overcomes many of the disadvantages of both the small, controlled study (in which too few patients participate to provide meaningful information about side effects) and the large, uncontrolled study (where bias in reporting and missing information seriously impair the data obtained).

THE INTERACTION OF MORPHINE AND D-TUBOCURARINE ON RESPIRATION AND GRIP STRENGTH IN MAN.

In healthy male volunteers, morphine in combination with d‐tubocurarine produces a greater decrease in responsiveness to end expiratory carbon dioxide than does morphine alone.

A comparison of the respiratory depressant effects of dextropropoxyphene and codeine in man

Twelve volunteers were given placebo and graded doses of codeine and dextropropoxyphene to determine the relative respiratory potency of oral dextropropoxyphene and oral codeine. Carbon dioxide response curves were prepared from data accumulated with a rebreathing technique. The relative respiratory potency, p, was calculated as 0.33. According to this calculation, 180 mg. of dextropropoxyphene administered orally produces respiratory depression equal to that of 60 mg. of codeine orally.

The interaction of morphine and nalorphine on respiration

A study was carried out in volunteers to determine the relative potency as respiratory depressants of nalorphine and morphine and their interaction when administered together. The relative potency of nalorphine when compared to morphine was found to be 0.74 (13.5 mg. nalorphine ≎ 10 mg. morphine). The data are consistent with the hypothesis that antagonism of the respiratory effects of morphine by nalorphine is related primarily to differences in intrinsic activity of the drugs and not solely in their receptor affinity. Thus, their interaction could be classified as competitive dualism.

An on-line hybrid computing system for dynamic respiratory response studies☆

This paper describes a hybrid computing system for on-line human respiratory studies. A digital computer dictates the subjects inspired CO2 concentration through a servocontrolled breathing chamber. The inspired CO2 is varied so that the alveolar CO2 concentration has a useful dynamic perturbation. A special purpose analog computer system measures and displays respiratory response data in real time and an on-line digital system accumulates these data on a breath-to-breath basis. A digitally controlled breath sound simulator is used to study the subjects voluntary interaction with his involuntary CO2 response. Examples of experimental data are presented. The system is presently in use in ongoing studies of the normal and drug-altered respiratory control system.

The respiratory effects of codeine and morphine in man

A controlled study was carried out in human volunteers to compare the respiratory effects of codeine and morphine administered intramuscularly and codeine administered orally and intram1lScularly. Codeine intramuscularly was found to be 0.1 as potent as morphine. Oral codeine was 0.72 as potent as intramuscular codeine. These relative potency estimates are in close agreement to those published for analgesic relative potency. It is concluded that when intramuscular morphine and codeine or oral and intramuscular codeine are given in equianalgesic doses, similar degrees of respiratory depression are induced.

The hypnotic effects of codeine and secobarbital and their interaction in man

Codeine and secobarbital and a combination of the two were studied as nighttime hypnotics. There was a positive dose effect between 60 and 180 mg. of secobarbital, but increasing the dose of codeine from 30 to 90 mg. appeared to show a stimulant effect on onset and duration of sleep. Taken together, codeine plus secobarbital were more effective than was secobarbital alone. Analysis indicated that this interaction represented synergism.