Inhibitory Effect of Chlorpromazine upon the Adrenal Cortical Response to Insulin Hypoglycemia in Man1

Christy, Nicholas P.; Longson, Donald; Horwitz, William A.; Knight, Mary M.

doi:10.1172/jci103452

Cited by 43 publications

(17 citation statements)

References 23 publications

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“…Analytic methods. Free plasma 17-OH-corticosteroid levels were determined by the Silber-Porter method (25) as modified in this laboratory (26). Plasma workers (20).…”

Section: Methodsmentioning

confidence: 99%

On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

Christy¹,

Wallace²,

W³

et al. 1959

J. Clin. Invest.

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The question of whether or not there is an increase in adrenal cortical secretion during pregnancy remains unsettled. Morphologic studies of the adrenal during gestation have revealed enlargement of the gland in some species (1) and no enlargement in others (2). In the human female, several groups of investigators have observed a progressive rise in the plasma 17-hydroxycorticosteroid (17-OH-corticosteroid) level during pregnancy (3-8). Paper chromatographic studies (9), confirmed in this laboratory (10), have indicated that the elevated plasma 17-OH-corticosteroid level is due to an increase in circulating hydrocortisone, and not to a nonspecific chromogen. Measurement of urinary 17-OH-corticosteroids has given equivocal results. Jayle, Desgrez, Serpicelli and Rozeg (11), Devis (12), Mills (13), and Appleby and Norymberski (14) found that the rise in urinary 17-OH-corticosteroids and 17-ketogenic steroids during pregnancy was of only moderate degree. Contradictory results have been obtained from studies of urinary 11-oxygenated 17-ketosteroids, the principal C19 metabolites of hydrocortisone (15). Dobriner, Lieberman, Rhoads and Taylor (16) crepancy between the finding of elevated plasma and of relatively normal urinary 17-OH-corticosteroid levels in pregnancy, Migeon, Bertrand and Wall investigated the rate of disappearance of injected 4-C14-hydrocortisone from plasma of pregnant women near term and found it to be delayed (20). These workers also observed a reduced rate of appearance of plasma and urine 17-OHcorticosteroid conjugates (glucuronides) after the administration of labeled hydrocortisone. These data suggested that the co-existence of high plasma (unconjugated) 17-OH-corticosteroid values and normal urine (unconjugated plus conjugated) 17-OH-corticosteroid values might be partly explained by the presence in both plasma and urine of a greater proportion of free hydrocortisone and a smaller proportion of conjugated hydrocortisone metabolites than normal (20). Devis (12) and Gray (21) have reported increased amounts of free 17-OH-corticosteroid in the urine of pregnant women. The present report describes studies upon the rate of hydrocortisone clearance from plasma in late pregnancy and in Laennec's cirrhosis, a condition in which hydrocortisone disposal rate is reportedly delayed (22)(23)(24). The data suggest that a delay in hydrocortisone clearance may not completely account for the elevated plasma 17-OHcorticosteroid levels observed in the pregnant state. MATERIALS AND METHODSPatients. Subjects were pregnant women in the third trimester of pregnancy who were not acutely ill and who showed no evidence of rheumatic heart disease, diabetes mellitus or pre-eclampsia. The women were hospitalized for premature rupture of the membranes or in anticipation of elective Caesarian section. Patients with Laennec's cirrhosis were six men and one woman with the typical clinical and laboratory features of parenchy-299

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“…Analytic methods. Free plasma 17-OH-corticosteroid levels were determined by the Silber-Porter method (25) as modified in this laboratory (26). Plasma workers (20).…”

Section: Methodsmentioning

confidence: 99%

On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

Christy¹,

Wallace²,

W³

et al. 1959

J. Clin. Invest.

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“…The hypoglycemic state is combated by the counterregulatory release of epinephrine (23), adrenocorticosteroids (24), and glucagon (25). Epinephrine and cortisol strongly inhibit the enhancing effect of insulin on glucose uptake by rat diaphragm (26,27), wherefore their presence in excess in test plasmas could have blunted the full betacytotropic effects of sulfonylurea agents.…”

Section: Comparison Of Insulagenic Potenciesmentioning

confidence: 99%

Quantitative Effects of Glucose, Sulfonylureas, Salicylate, and Indole-3-Acetic Acid on the Secretion of Insulin Activity Into Pancreatic Venous Blood*

Seltzer¹

1962

J. Clin. Invest.

161

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It is now clear that the predominant metabolic effect of sulfonylurea compounds is to release insulin from pancreatic beta cells. In addition, assays by Yalow, Black, Villazon and Berson (1) of insulin concentrations in peripheral blood indicate that the secretory potency of sulfonylureas is substantially weaker than that of glucose. More quantitative comparison of insulin-releasing activities of individual substances, however, requires knowledge of both the concentration of insulin in pancreatic venous blood, and the latter's rate of flow. A suitable closed circuit enabling these measurements was devised by Metz (2), who determined total insulin outflow from the pancreaticoduodenal vein draining the right pancreatic limb in dogs during glucose infusion into the femoral vein. The latter technic was employed in the present study to determine total secretion of insulin activity from a segment of dog pancreas for 30 minutes after glucose or a hypoglycemia-inducing agent was injected into a peripheral vein. Although glucose and three sulfonylurea compounds all promptly initiated release of insulin, glucose was by far the most potent insulogenic substance. In contrast, neither salicylate nor indole-3-acetic acid altered the rate of insulin secretion. METHODSMongrel dogs of either sex, weighing between 10 and 15 kg, were used in all experiments. During a quarantine period of 14 days, animals were metabolically stabilized on a daily ration of meat and Purina laboratory chow, which provided approximately 60 g protein, 20 g fat and 90 g carbohydrate. In early experiments, intact dogs were used after a 24-hour fasting period.

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“…G-s Cristy et al 15 reported a diminished adrenoeortical response to insulin hypoglycaemia in chlorpromazine-treated patients; Gold et al 1~ observed that chlorpromazine decreased the response to injections of metyrapone (su-4885), although the response to operation was unaffected. Sloane et aI.…”

Section: Discussionmentioning

confidence: 99%

An objective evaluation of tranquillizers as preanaesthetic medication: effect on adrenocortical function

Oyama

Kimura

Takazawa

et al. 1969

Can. Anaes. Soc. J.

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BECAUSE a large number of patients seem to be anxious before operation, 1,~ understanding of the emotional problems of surgical patients by anaesthesiologists is important for the improvement of their care. Most workers ~-5 have been in general agreement that the anxiety experienced by patients preoperatively causes no significant effect on the adrenocortical function. However, we recently found that preoperative apprehension as a stress does elicit adrenocortical stimulation judged by the peripheral plasma cortisol level. It was also demonstrated that the circulating cortisol level is a useful parameter for the objective evaluation of premedicating drugs. ~ Due to differences in the species studied, the experimental design, and the validity of methods of analysis, there is considerable debate about the specific effect of tranquillizing drugs, reserpine and chlorpromazine, on the adrenocortical activity. 6-s The present study of 54 patients, therefore, was undertaken first to investigate the sedative effects of tranquillizing drugs such as hydroxyzine (Atarax, Vistaril), diazepam (Cercine, Horizone, Valium), and nitrazepam (Nelbon, Benzalin, Mogadon) in preoperative patients, and second to correlate subjective sedation by these agents with alterations in adrenocortical activity. METHODSFifty-four patients who underwent operations were the subjects of the study. They ranged from 15 to 60 years of age and were free from endocrine, renal, and hepatic disease. The operations were scheduled to start at 9:00 A~. Premedication was administered by mouth at 8:00 PM on the day before operation and 7:00 A~ on the day of operation, just after the first blood sampling. Eleven patients who served as a placebo group received 2 tablets of maltose. Hydroxyzine (2.5 mg/kg) was administered to 14 patients; 15 patients took diazepam (0.2 mg/kg) and 14 patients had nitrazepam (0.2 mg/kg). All received atropine 0.25 mg intravenously and intramuscularly at 8:30 AN before induction and just after the last blood sampling. Subjective evaluations were made by asking whether the patients could sleep, had fear or concerns about their operations, or felt drowsy. These questionnaires were employed just prior to induction in the operating room, where the data were collected by the double-blind method.

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Inhibitory Effect of Chlorpromazine upon the Adrenal Cortical Response to Insulin Hypoglycemia in Man1

Cited by 43 publications

References 23 publications

On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

Quantitative Effects of Glucose, Sulfonylureas, Salicylate, and Indole-3-Acetic Acid on the Secretion of Insulin Activity Into Pancreatic Venous Blood*

An objective evaluation of tranquillizers as preanaesthetic medication: effect on adrenocortical function

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