Chlorpromazine Therapy Research Articles

Chlorpromazine Metabolism VIII: Blood Levels of Chlorpromazine and Its Sulfoxide in Schizophrenic Patients

A procedure was standardized for extracting chlorpromazine and its sulfoxide from the blood and for applying a recently developed fluorometric assay method to determine blood levels of these two compounds in schizophrenic patients receiving chlorpromazine therapy. The described methodology opens avenues for performing bioavailability and generic equivalence studies in humans.

Heat illness. II. Pathogenesis

The effects of elevated temperatures and the time-temperature combinations for irreversible damage are outlined. Coagulation abnormalities and the effects on the kidney, liver, heart, brain and serum enzymes, the role of electrolytes and water, including salt deficiency and the controversial question of salt supplements, potassium deficiency, changes in other electrolytes and sweat solutes, and rhabdomyolysis (including a discussion of experimental work on dogs) are reviewed. The section ends with a discussion of the effects of drugs and an account of a recent fatal case of heat stroke which may have been triggered by chlorpromazine therapy.

Effects of Chlorpromazine on Bilirubin Metabolism and Biliary Secretion in the Rat

Chlorpromazine (CPZ) is a long recognized cause of jaundice, but the mechanism by which this agent produces icteric liver disease is not well defined. This study examined some effects of CPZ administration on bilirubin metabolism and biliary secretion in the rat. Acute CPZ treatment (25 mg per kg intravenously) produced hemolysis and resulted in increased bilirubin output and stimulation of hepatic heme synthesis. Both unconjugated bilirubin and a gamma-azopigment found primarily in obstructed rat bile were seen. Acute infusion of hemoglobin solutions to simulate the hemolysis produced by acute CPZ treatment resulted in increased bilirubin output and increased hepatic heme synthesis, but no alterations in the normal conjugation pattern of bilirubin in bile were seen. Chronic CPZ treatment for 4 and 8 days (25 mg per kg intraperitoneally) increased bilirubin output without elevating plasma hemoglobin levels and increased the fraction of monoconjugated bilirubin in bile; the 8-day chronic treatment regimen also caused unconjugated bilirubin to appear in bile. No change in liver weight, bile salt, phospholipid, or cholesterol output was seen with chronic CPZ therapy. Changes in bilirubin production and conjugation caused by CPZ may be a contributing factor in this agent's hepatotoxicity.

Chlorpromazine therapy, and associated acute disturbances of cardiac rhythm.

Chlorpromazine therapy, and associated acute disturbances of cardiac rhythm.

EFFECT OF NARCOTIC WITHDRAWAL ON NEONATAL SLEEP PATTERNS

It is known that morphine and related compounds suppress REM sleep in the adult. This study was undertaken to determine if infants of heroin and methadone-addicted mothers would exhibit altered sleep patterns in withdrawal. EOG, EMG, and respiration were recorded by multichannel polygraph on 10 infants (4 methadone, 6 heroin) for 2½-4 hr. periods prior to, during, and after chlorpromazine therapy (2.0 mg/kg/d).It was found that heroin and methadone obliterated REM sleep and that periods of quiet sleep were rare before treatment. After a minimum of 48 hrs. therapy, brief but identifiable periods of REM appeared, increasing in frequency as successful withdrawal occurred. However REM occupied a maximum of 5% of sleep time.Since this state is normally present in the newborn and is thought to be that period of sleep in which neuronal protein synthesis is most active, and since heroin and methadone suppress REM, it was concluded that suitable treatment of withdrawal is essential, not simply to relieve symptoms, but also to promote more normal and necessary sleep patterns during this critical time of brain development. This may, indeed, be especially valuable for those infants already demonstrating intrauterine growth retardation with maternal addiction.

Childhood acromegaly: successful therapy with conventional radiation and effects of chlorpromazine on growth hormone and prolactin secretion.

ABSTRACT A pre-adolescent girl with gigantism is described in whom growth hormone, insulin, prolactin, thyrotropin and triiodothyronine measurements have been performed prior to conventional radiation therapy. An acute and chronic (62 days) trial and evaluation of chlorpromazine failed to decrease growth hormone or increase prolactin concentrations. Radiation therapy was associated with a prompt return to normal levels of fasting growth hormone concentrations 3 months following 5000 rad administration. A lack of fall in growth hormone levels while on chlorpromazine therapy suggests that chronic treatment with this drug is ineffective. Conventional x-ray therapy in this patient with childhood acromegaly was effective and may be the treatment of choice when non-invasive therapy is indicated.

Increased growth hormone in partial and total lipoatrophy.

Since some clinical and metabolic features of lipoatrophy suggest increased human growth hormone (HGH) activity, we studied HGH responses in five patients with partial or total lipoatrophy. Two patients with total lipoatrophy had elevated basal levels of HGH of 80 and 25 ng. per milliliter, while two with partial lipoatrophy had abnormally high levels after arginine stimulation. The elevated levels seemed to correlate with the clinical activity of the disease. In one of the patients there was a slowing of the growth rate and a moderate weight gain after long-term chlorpromazine therapy decreased HGH levels; a comparison of the immunoreactive HGH in her serum with that from a normal patient by serial dilution technics suggested that the two were immunologically identical, and chromatographic mobilities were also identical. Oral glucose suppressed elevated HGH in all of the patients. These studies suggest that HGH levels are elevated intermittently in lipoatrophic patients and that the increase may contribute to some features of the disease.

PLASMA PROLACTIN ACTIVITY IN INAPPROPRIATE LACTATION

FORSYTH, ISABEL A.; BESSER, G. M.; EDWARDS, C. R. W.; FRANCIS, LYNN; MYRES, RITA P. Author Information

THE EFFECT OF CHLOROQUINE, CHLORPROMAZINE AND ULTRAVIOLET RADIATION ON THE CORNEAS OF PIGMENTED RABBITS

Following seven months of chloroquine or chlorpromazine administration in combination with chronic exposure to ultraviolet radiation, chloroquine and chlorpromazine keratopathy could not be produced in the pigmented rabbit. No measurable amounts of chloroquine or chlorpromazine were found in the experimental corneas. The hypothesis, that corneal changes seen in human beings following chloroquine or chlorpromazine therapy were unable to be reproduced in the laboratory animal because these changes were actinic radiation dependent, was not borne out, at least within the limits of this experiment.

Plasma prolactin activity in inappropriate lactation.

Using a bioassay dependent on the development of a lactogenic response in rabbit mammary tissue cultured in vitro, prolactin distinct from immunoreactive growth hormone has been found in the plasma of patients of both sexes with inappropriate lactation with and without evidence of pituitary tumours. It has also been found in one patient with primary hypothyroidism and galactorrhoea, and in another during chlorpromazine therapy, but not in nine patients with gynaecomastia without galactorrhoea. Plasma prolactin levels were examined in seven patients during oral glucose tolerance tests: no change occurred in the four patients with pituitary tumours, but the levels were suppressed in the three patients with normal pituitary fossae. Prolactin appears to be a distinct pituitary hormone in man, as in animals, and also to be aetiologically related to states of inappropriate lactation.

Lithium carbonate as a mood and total body water stabilizer.

LITHIUM carbonate has been increasingly used in psychiatry since 1949. 1 The evidence so far suggests that it is effective in at least a proportion of patients suffering from manic-depressive illness, and more recently interest in lithium carbonate has turned to the possibility that it acts prophylactically in some patients. 2-3 It is felt that it prevents the large and recurrent mood swings which might otherwise occur, but knowledge of its action is scanty. In view of its potential serious toxic effects when given to patients, 4,5 further information about its action is needed. Platman and Fieve 6 , have again noted that none of the current biological hypotheses in the affective disorders provides a satisfactory explanation for the clinical efficacy of lithium carbonate and they have emphasized that there are problems when there is concomitant chlorpromazine therapy. Its effect on

Glucose tolerance in man during chlorpromazine therapy.

Neither brief nor long chlorpromazine therapy appears to impair carbohydrate tolerance in hospitalized, mentally ill men under fifty yėars of age, as measured by a 100-gm., three-hour, oral glucose tolerance test.

Rabbit as a model for chlorpromazine-induced hyperpigmentation of the skin

Hyperpigmentation of exposed skin areas, comparable to that seen in less than 1 per cent of patients chronically dosed with chlorpromazine after intensive long-term therapy, has been produced in sixteen out of sixteen chronically dosed pigmented rabbits, receiving between 20–30 mg/kg per day. Thirty-min u.v. irradiation of a clipped or shaved area produced clear-cut hyperpigmentation of naturally pigmented skin areas in about 4 weeks. The characteristic occurrence of granular pigment in the dermis which is normally free of pigment was also observed. Hyperpigmented rabbits did not develop any concomitant ocular pathology, as seen in some patients on long-term, high-dosage chlorpromazine therapy.

Optic atrophy during chlorpromazine therapy.

Optic atrophy during chlorpromazine therapy.

Chlorpromazine therapy in a female albino mental patient: Clinical, histochemical and biochemical observations

Chlorpromazine therapy in a female albino mental patient: Clinical, histochemical and biochemical observations

The evaluation of chlorpromazine therapy in chronic schizophrenic women: A replicated experiment

The evaluation of chlorpromazine therapy in chronic schizophrenic women: A replicated experiment

Effects of caloric restriction on behavior and body weight during chlorpromazine therapy

Effects of caloric restriction on behavior and body weight during chlorpromazine therapy

Phenothiazines and diabetes in hospitalized women.

Between 1955 and 1966 the prevalence of diabetes among hospitalized psychotic women patients rose from 4.2 to 17.2 percent. The increase followed the introduction of chlorpromazine therapy in 1954. About every fourth patient who had been treated for one year or longer with more than 100 mg. daily of chlorpromazine or corresponding doses of another psychoactive pheno thiazine developed hyperglycemia and glycosuria. The disturbance resembled adult-onset diabetes, but there were fewer complications. In 25 percent of the patients remissions occurred either after withdrawal of the drug or reduction in dosage. Obese patients over 50 years old and those with a family history of diabetes were more often affected. Patients with paranoid schizophrenic reaction developed diabetes after phenothiazine therapy relatively more frequently than did those with other forms of schizophrenic reactions or with nonschizophrenic psychiatric diagnoses.

The Effect of Chlorpromazine on Oculocutaneous Pigmentation in the Guinea Pig

In March, 1964, Greiner and Berry (1) described in detail their observations of 70 patients with abnormal oculocutaneous pigmentation following long-term, high dose chlorpromazine therapy. They first noted this phenomenon in 1958. Several common factors were found in most patients; the majority were Caucasians with very fair skin, and had histories of prolonged sunlight exposure. Most of the patients were females and all of these were amenorrheic. The principal neuropsychiatrie disorders for which the drug was given were schizophrenia and mental deficiency. All patients had received very large, daily doses of chlorpromazine. Other authors have subsequently reported similar findings (2-7). The object of the present work was to attempt to reproduce the oculocutaneous pigmentation in the guinea pig. Once a suitable experimental technic was developed, it was hoped to elucidate the cause of the pigmentary defect and if possible the exact chemical nature of the pigment.

Depression of erythropoiesis associated with chlorpromazine therapy

Depression of erythropoiesis associated with chlorpromazine therapy