Anticholinergic prophylaxis in young adults treated with neuroleptic drugs.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C R Lake
Publications and source records attributed to C R Lake.
Effects of naloxone and thyrotropin-releasing hormone on plasma catecholamines, corticosterone, and arterial pressure in normal and endotoxemic rats.
To investigate the possible involvement of the adrenal cortex and medulla in the cardiovascular effects of naloxone and thyrotropin-releasing hormone (TRH) in endotoxic shock, plasma epinephrine, norepinephrine, dopamine, and corticosterone were measured along with hemodynamic variables during naloxone and TRH treatment of normal and endotoxemic rats. In the absence of endotoxemia, naloxone (3 mg/kg, iv) did not significantly alter mean arterial pressure or plasma catecholamine or corticosterone levels. In contrast, following TRH administration (4 mg/kg, iv), an increase in mean arterial pressure was associated with significant increases in plasma epinephrine, norepinephrine, and corticosterone. TRH also produced a transient increase in plasma glucose levels. Endotoxic shock was associated with marked increases in plasma catecholamine levels, with epinephrine levels showing the greatest change, and significant though less pronounced increases in corticosterone. Both naloxone and TRH significantly elevated mean arterial pressures of endotoxemic rats, although neither of these compounds significantly altered the plasma catecholamine and corticosterone responses to endotoxin. Naloxone and TRH also failed to alter endotoxin-induced changes in plasma glucose levels. These results indicate that the cardiovascular effects of naloxone and TRH in endotoxic shock do not simply arise from an enhancement of adrenal catecholamine or corticosterone secretion.
Animals↗
Effects of alcohol on cerebrospinal fluid norepinephrine in rhesus monkeys.
Alcohol (1-3 g/kg) significantly increased the concentration of cerebrospinal fluid (CSF) norepinephrine (NE) in rhesus monkeys. This effect is consistent with the previously demonstrated activational and possible antidepressant effect of low doses of alcohol. The greatest increase was observed in subjects with low baseline levels of CSF NE. Individual differences in activation or euphoria could be related to differential increases in CSF NE following alcohol consumption.
Alcohol Drinking↗
Effects of carbamazepine on noradrenergic mechanisms in affectively ill patients.
Noradrenergic mechanisms have been postulated to account for the anticonvulsant and psychotropic effects of carbamazepine. In order to assess this possibility in man, cerebrospinal fluid (CSF) was obtained from affectively ill patients before and during treatment with carbamazepine (average duration 29 days) at doses averaging 860 mg/day, achieving blood levels of 8.86 micrograms/ml. Neither plasma nor CSF norepinephrine (NE) nor CSF 3-methoxy-4-hydroxy-phenylglycol (MHPG) was significantly altered by carbamazepine. Baseline medication-free values in 21 depressed patients were not predictive of the degree of subsequent clinical antidepressant response. CSF NE decreased in four manic patients treated with carbamazepine. The many effects of carbamazepine on noradrenergic mechanisms in animals are discussed in relationship to these first studies of carbamazepine in man.
Affective Disorders, Psychotic↗
Altered norepinephrine metabolism following long-term weight recovery in patients with anorexia nervosa.
This study evaluated the relationship between noradrenergic function and long-term weight recovery in patients with anorexia nervosa. Eleven patients with long-term weight maintenance (6 to 72 months) had lower plasma and cerebrospinal fluid concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol than did healthy controls. Reduced noradrenergic activity may be associated with long-term stability of weight recovery in patients with anorexia nervosa.
Adolescent↗
Biological alterations in the primary affective disorders and other tricyclic-responsive disorders.
Noradrenergic function was studied in patients with primary affective disorder and other tricyclic-responsive disorders including obsessive-compulsive disorder, anorexia nervosa and panic attack/agoraphobia in medication-free states. Pre-synaptic noradrenergic activity was assessed by assaying plasma concentrations of norepinephrine (NE) and its metabolite 3-methoxy,4-hydroxyphenylglycol (MHPG). Noradrenergic receptor responsiveness was evaluated by measuring plasma growth hormone (GH), MHPG, and NE responses to clonidine. Binding of tritiated dihydroergocriptine (3H-DHE) and biochemical responsiveness of alpha 2-adrenergic receptors were measured in platelet preparations. These studies suggest that noradrenergic activity may be altered in several tricyclic-responsive disorders and are consistent with the possibility that tricyclic antidepressants may serve to stabilize a dysregulated noradrenergic system in patients from several diagnostic categories.
Adult↗
A longitudinal evaluation of thyroid function in critically ill surgical patients.
Thyroid hormone alterations (known as the "sick-euthyroid syndrome") are common following major surgery, but the time course for appearance and recovery from these alterations has not previously been longitudinally studied in a large group of surgical patients. The authors prospectively studied 59 patients undergoing major surgery (coronary artery bypass grafting, pneumonectomy, or subtotal colectomy). Compared with preoperative values, the mean serum T4, T3, free T3, and TSH concentrations decreased significantly (p less than 0.05) following surgery. Serum reverse T3 and T3 resin uptake index increased, while free T4 levels remained unchanged. These changes were seen within 6 hours of surgery and normalized by 1 week after surgery. Although the serum TSH response to TRH was normal before and after surgery in 56 of the 59 patients, the maximal TRH-induced increase in serum TSH and the integrated serum TSH response to TRH were suppressed in the early perioperative period. This postoperative TSH suppression correlated with elevated postoperative plasma dopamine concentrations (r = 0.57, p less than 0.05). Three patients with compensated primary hypothyroidism were detected in the study and represent the first documentation of serial thyroid hormone and TSH levels in hypothyroid patients undergoing major surgery. These patients had similar changes in thyroid hormone values compared with euthyroid patients. The serum TSH response to TRH was suppressed into the normal range in two of these patients on the day following surgery. The authors conclude that the sick-euthyroid syndrome occurs within a few hours of major surgery and remits with convalescence. Postoperative decreases in serum TSH may mask the diagnosis of hypothyroidism. Surgical consultants should be aware of these rapid postoperative changes so that thyroid function tests are properly interpreted in patients who have undergone major surgery.
Adult↗
The hemodynamic and plasma catecholamine responses to routine restorative dental care.
Eleven healthy, normotensive males undergoing routine restorative dental care were evaluated during treatment for possible hemodynamic alterations in response to potential sympathetic nervous system stimulation. It is concluded that once acceptable local anesthesia is achieved, the hemodynamic and sympathetic responses to routine restorative dental care are minimal. These findings serve as a baseline for further studies evaluating the response of medically and pharmacologically compromised patients to similar dental procedures.
Adult↗
Disturbances of norepinephrine metabolism and alpha-2 adrenergic receptor activity in anorexia nervosa: relationship to nutritional state.
Explore the source record for details and available documents.
Adult↗
The effects of dopamine agonists on human cardiovascular and sympathetic nervous systems.
We gave people four different dopamine agonists and monitored blood pressure, heart rate and circulating catecholamine levels. Bromocriptine decreased blood pressure and plasma norepinephrine levels. Dopamine increased pulse pressure, heart rate and circulating epinephrine (E) and norepinephrine (NE) levels. Dopamine agonists tend to diminish blood pressure by inhibiting sympathetic neuronal discharge of NE and, to a lesser extent, by stimulating dopamine vascular receptors. However, dopamine and L-dopa can be converted to NE and E, both of which have pressor effects. The complex cardiovascular effects of dopamine agonists are the result of stimulation of dopamine vascular and neuronal receptors and the production of NE and E.
Adult↗
Hemodynamic and plasma catecholamine responses to epinephrine-containing perianal lidocaine anesthesia.
Despite the frequent use of large volumes (30-40 ml) of epinephrine-containing local anesthetic solutions for ano-rectal surgery, little is known about the anesthetic-induced hemodynamic consequences. Therefore, we measured the heart rate, blood pressure, and plasma catecholamine (norepinephrine and epinephrine) responses to the perianal injection of 40 ml of 0.5% lidocaine alone (n = 8) or 0.5% lidocaine with 1:200,000 epinephrine (n = 10) in 18 healthy adults undergoing outpatient ano-rectal surgery. The mean +/- SEM plasma epinephrine concentration increased from a baseline of 42 +/- 7 pg/ml to a peak of 622 +/- 94 pg/ml 4 min after injection of epinephrine-containing anesthetic (P less than 0.001), whereas lidocaine alone increased the mean plasma value from 36 +/- 9 pg/ml (baseline) to only 69 +/- 16 pg/ml (not significantly different) at its peak. Despite the increases in plasma epinephrine levels in the group receiving epinephrine-containing anesthesia, no changes in blood pressure, heart rate, or plasma norepinephrine levels were observed. Given the advantages (including prolongation of the duration of anesthesia) of adding epinephrine to perianal local anesthetics, our data support its safe use in healthy adults.
Adult↗
Plasma cortisol responses to clonidine in depressed patients and controls. Evidence for a possible alteration in noradrenergic-neuroendocrine relationships.
Plasma cortisol responses to the intravenous administration of clonidine hydrochloride and placebo were evaluated in depressed patients and controls. Depressed patients had higher mean baseline cortisol levels than controls. Cortisol levels decreased during the morning study period following both placebo and 2 micrograms/kg of clonidine hydrochloride in the depressed patients, but the cortisol decrease was sixfold greater on the day of clonidine administration; these placebo-clonidine differences were statistically significant, whether calculated on an absolute decrement basis or as a percent change. In contrast, controls responded to clonidine with only a 1.5-fold greater cortisol reduction than that found after placebo, a nonsignificant difference from the day of placebo administration. Reductions in the concentration of plasma 3-methoxy-4-hydroxyphenylglycol following clonidine administration were significantly negatively correlated with baseline plasma cortisol levels, raising the possibility that abnormalities in the responsiveness of the alpha 2-noradrenergic system may be associated with the hypothalamo-pituitary-adrenal (HPA) axis dysfunction found in depressed patients.
Aged↗
Dystonia in 61-year-old identical twins: observations over 45 years.
We examined 61-year-old identical twin women of Jewish extraction with a probable autosomal recessive form of torsion dystonia. The dystonia in each was relatively mild and discovered only because a young relative developed dystonia. The twins were said to be discordant for dystonia, but personal evaluation led to the diagnosis of dystonia in both. Their slow course, with prolonged spontaneous remission in one twin, is in contrast to that described in most published reports. Although similar in mode of onset and initial course, the twins were dissimilar in age at onset, influence of pregnancy, diurnal variation in symptoms, need for medication, later course, and degree of disability at age 61. Normal plasma levels of norepinephrine and dopamine-beta-hydroxylase are consistent with autosomal recessive hereditary torsion dystonia. The importance of personal evaluation of key family members in establishing the correct genetic basis for a heterogeneous group of disorders, such as the hereditary dystonias, is stressed.
Chromosome Aberrations↗
Hypersensitivity to d-amphetamine several years after early social deprivation in rhesus monkeys.
Social deprivation of rhesus monkeys in infancy results in increased sensitivity to psychotic-like behavioral effects of low doses of d-amphetamine given 2-3 years later. These behavioral effects are associated with increased levels of CSF norepinephrine. These data suggest that social developmental factors could be partially responsible for variation in neurochemical responses and long-lasting differential sensitivity of primates to the psychosis-inducing effects of d-amphetamine.
Analysis of Variance↗
Plasma catecholamine and hemodynamic responses to the placement of epinephrine-impregnated gingival retraction cord.
A double-blind randomized crossover study was conducted to measure the changes in heart rate, mean arterial blood pressure, pulse pressure product, and plasma catecholamine levels for 60 minutes after the placement of racemic (r) epinephrine- or alum-impregnated retraction cords in intact gingival sulci of nine healthy volunteers. The r-epinephrine-impregnated cord produced significant (p less than 0.01) increases in plasma epinephrine concentrations after 60 minutes, but there were no epinephrine-induced hemodynamic changes. According to these findings, r-epinephrine-impregnated gingival retraction cord placed in an intact, nonlacerated gingival sulcus in a healthy young adult should produce no significant hemodynamic response. It is not known how the placement of epinephrine-impregnated retraction cord would affect elderly or medically compromised patients or patients with lacerated or periodontally involved gingivae.
Adult↗
Platelet alpha-adrenergic binding and biochemical responsiveness in depressed patients and controls.
In a study of platelet alpha 2-adrenergic receptor number in depressed patients, binding of tritiated dihydroergocriptine (3H-DHE) to platelet membranes was measured in 23 depressed patients and 51 controls. To examine the functional responsiveness of the platelet alpha 2-adrenergic receptor, basal cyclic adenosine 3',5'-monophosphate (cAMP) production, prostaglandin E1 (PGE1) stimulation of cAMP production, and norepinephrine (NE) inhibition of PGE1-stimulated cAMP production were measured in 23 depressed patients and 53 control subjects. Finally, plasma NE concentration was measured in 20 patients to explore the possible relationship between this endogenous agonist and platelet alpha 2-adrenergic receptor function. 3H-DHE binding to platelet membranes was significantly increased in the depressed patients compared to control subjects. Both the PGE1-stimulated cAMP response and the inhibition of this response by NE were significantly reduced in the depressed patients compared to the control subjects. Thus, an apparent dissociation between alpha 2-adrenergic receptor binding and functional responsiveness was observed. Plasma NE concentrations were neither significantly different in the depressed patients than in the controls nor correlated with any of the measures of cAMP responsiveness. They were, however, significantly negatively correlated with 3H-DHE binding in depressed patients with adequate PGE1 stimulation of cAMP production.
Adult↗
Cerebrospinal fluid measures of neurotransmitter changes associated with pharmacological alteration of the despair response to social separation in rhesus monkeys.
Social separation is a risk factor for major depressions that can be modeled in nonhuman primates. Changes in central monoamine neurotransmission are also likely to be involved in major depression. This study examined the relationship between separation-induced depressive-like behavior and central monoamine neurotransmitter changes in rhesus monkeys. Measures of cerebrospinal fluid (CSF) norepinephrine (NE), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were used to assess the neurobiological impact of social separation and drug treatments alone or in combination. alpha-Methyl-p-tyrosine exacerbated, and fusaric acid ameliorated, the depressive-like response to separation. Probenecid-induced accumulations of HVA and 5HIAA reflected changes in behavior, but were not consistently affected by drug treatment. In contrast, pretreatment CSF NE was comparatively stable across repeated sampling, and drug-induced changes in this measure were correlated with changes in behavior. Low CSF NE, whether drug-induced or naturally occurring, was associated with a more severe depressive-like response to separation.
Animals↗
Increased circulating plasma norepinephrine concentrations in noncardiac causes of pulmonary hypertension.
Sympathetic nervous system (SNS) activity and circulating norepinephrine (NE) levels may play roles in the elevated pulmonary vascular resistance (PVR) found in patients with pulmonary hypertension. To study the relationship between plasma NE levels, pulmonary NE metabolism, and pulmonary hypertension, we studied 9 patients, suspected of having noncardiac causes of pulmonary hypertension, before and after vasodilator therapy with phentolamine, nitroglycerin, isoproterenol, or hydralazine. Patients were admitted to the ICU and studied using pulmonary artery thermodilution catheters. Seven of 9 patients had noncardiogenic pulmonary hypertension whereas 2 patients did not have hemodynamic evidence of pulmonary hypertension. Simultaneous pulmonary and radial artery samples were analyzed for plasma NE and epinephrine (EPI) content before and after various vasodilator agents. Baseline pulmonary artery (PA) and radial artery NE concentrations correlated (r = .72) with PVR, PA pressures, and PA minus pulmonary capillary wedge (WP) pressures and were increased compared to the 2 patients with normal pulmonary pressures (p less than .01). The normal pulmonary extraction of circulating NE was absent in the 7 patients with pulmonary hypertension. PVR decreased significantly in all 7 patients with each vasodilator (p less than .05); however, the decrease was independent of any change in plasma NE concentration and therapy had no effect on the pulmonary extraction of circulating NE. These data indicate that elevations in plasma NE are coincident with the presence of noncardiogenic pulmonary hypertension and that acute pharmacologic reduction of PVR does not normalize the loss of pulmonary NE metabolism.
Adult↗