Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

"Dale's Principle" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative view that at each monoaminergic synapse the action of the transmitter is modulated by several metabolically related substances: amine analogs (2-phenylethylamine [PEA], p-tyramine, etc.), deaminated products (aldehydes, acids, and alcohols), and possibly also amino acid precursors. In support of this view, the authors present evidence for the presence, synthesis, metabolism, and biological activity (at the cellular level, using microelectrode techniques) of amino acid, amines, and deaminated compounds metabolically related to catecholamines and sorotonin. That neuroamino acids exert direct effects (not mediated via their amine metabolites) is illustrated by the rapid effects of microiontophoretic dopa upon cortical unit activity, and by the observation that neither the lethargic effect of 5-hydroxytryptophan (considered to support Jouvet's serotonergic theory of sleep) nor the behavioral stimulant effects of dopa (considered to support the catecholamine theory of affective behavior) are significantly prevented by L-aromatic amino acid decarboxylase inhibitors. The biological activity of the deaminated metabolites of catecholamines and serotonin is illustrated by the effects of their microiontophoretic administration upon cortical units. Further, probenecid (an inhibitor of acid transport across the blood-brain barrier) is shown to qualitatively alter the effects of intraventricularly administered PEA and of its metabolite phenylacetic acid upon visual evoked potentials. Rabbit brain is shown to synthesize a series of pharmacologically active noncatecholic phenylethylamines as by-products of catecholamine metabolism. Amine modulators such as PEA differ from typical transmitters by their ability to cross biological barriers; inhibition of decarboxylase in peripheral tissues only (using alpha-methyldopa hydrazine) markedly depletes brain PEA (but not catecholamines). Because of the homeostatic control of the rate of transmitter synthesis and disposition, physiological, pharmacological, and pathological changes may be expected to affect more the tissue levels of related modulators. This modulator theory of drug action is illustrated by the effect of several psychotropic drugs upon the brain levels of PEA and of norepinephrine. For instance, amphetamine initially decreases and then increases brain PEA levels, without altering brain norepinephrine levels. The authors propose an expanded "Dale's Principle": each neuron is specific in that it releases at all its endings the same pool of chemical messengers, composed of one transmitter and metabolically related modulators, the relative proportion of which is determined by the physiological state of the cell (biochemical plasticity)...
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PMID:Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle. 0 60

To determine if thiopental reduces the incidence of neurologic sequelae after coronary artery surgery, we prospectively studied 300 patients undergoing coronary artery bypass grafting. Patients who had no history of neurologic or psychiatric illness were randomly assigned to receive either a thiopental infusion or a saline placebo infusion beginning with the administration of heparin and ending just after aortic decannulation. The patients received an opioid-relaxant anesthetic administered by an anesthesiologist who was not involved in this investigation and who was blinded to the test infusion. One of the investigators infused either saline or thiopental to produce an isoelectric electroencephalogram with 30-45 s between bursts. Standardized neurologic examinations were performed preoperatively and on the 2nd and 5th postoperative days by one of the blinded investigators. The group of patients receiving thiopental required a longer time for awakening (6.4 +/- 3.9 vs. 4.0 +/- 2.4 h, mean +/- SD, P less than 0.05) and for tracheal extubation (22.4 +/- 18.4 vs. 17.4 +/- 9.6 h, P less than 0.05), and a greater number of these patients were lethargic on the 2nd postoperative day. More patients receiving thiopental required vasoconstrictors during the thiopental loading and cardiopulmonary bypass (CPB) periods, while a greater number of patients receiving placebo required vasodilators. A greater number of patients receiving thiopental required inotropic drugs during separation from CPB. Despite the above differences, only 2 of the 151 patients in the placebo group (1.3%) and 5 of the 149 patients in the thiopental group (3.3%) experienced strokes (P = 0.2535).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of thiopental on neurologic outcome following coronary artery bypass grafting. 200 Oct 15

Mania is a psychiatric illness that often requires immediate intervention, and the pregnant manic patient presents a therapeutic dilemma. Use of psychotropic medications during pregnancy may cause three complications: teratogenesis, neonatal toxicity, and behavioral toxicity. The literature contains few well-controlled studies for psychotropic medications in bipolar or other psychiatric populations and those often lack a control group or do not consider confounding factors such as other drug use. Pharmacologic alternatives include antipsychotics, lithium, carbamazepine, and benzodiazepines. Although studies and case reports describe fetal malformations in infants exposed in utero to psychotropic medications, the data are conflicting as to the nature of anomalies and risk of their occurrence. Malformations can occur in almost every organ system; however, the cardiovascular type are of major concern after lithium exposure during the first trimester and oral clefts after benzodiazepine exposure. Antipsychotic exposure can produce extrapyramidal symptoms in the neonate and lithium has been associated with neonatal cyanosis, lethargy, flaccidity, and non-toxic goiter. A neonatal abstinence syndrome has occurred after maternal benzodiazepine consumption. Behavioral toxicity is more difficult to assess, as long-term follow-up is needed. To date, evidence for behavioral toxicity in children exposed to lithium or antipsychotics in utero is lacking. Few specific guidelines for using psychotropic medications in an acutely manic pregnant patient exist. Current symptoms, past response, and the stage of gestation all must be considered. Complete elimination of symptoms may not be the goal. A team approach is essential in treatment of such a complex and challenging patient.
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PMID:Pharmacologic management of acute mania in pregnancy. 265 79

The cancerous patient who suffers a coinciding psychiatric illness shows, according to the M.M.P.I., signs of a depressive personality with marked introversion and dependence. The aggressivity test shows that self-aggressiveness coincides with inhibition and lethargy tone. An accumulation of stress factors and events stand out in patients with depression (72%), which do not appear in those patients diagnosed as having neuroses and schizophrenia. There is a need for psychiatric attention which contributes to treating the patient interdepartmentally; thus relieving both the moral and physical pain which these patients suffer.
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PMID:[Psychosomatics and cancer]. 277 91

Delirium (acute confusional states), a common and often overlooked psychiatric disorder, can occur at any age, but elderly persons are especially prone to develop it. In later life, it is often a conspicuous feature of systemic or cerebral disease and drug (notably anticholinergic) toxicity, and it may constitute a grave prognostic sign. Its development in a hospitalized patient may interfere with his or her management, disrupt ward routine, and cause medicolegal complications as a result of patient injury. Acute onset of a fluctuating level of awareness, accompanied by sleep-wake cycle disruption, lethargy or agitation, and nocturnal worsening of symptoms, are diagnostic. Early recognition of delirium and treatment of its underlying cause are essential.
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PMID:Delirium (acute confusional states). 362 89

The use of psychotropic drugs has been associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in a number of case reports. SIADH is characterised by the sustained release of antidiuretic hormone (ADH) from the posterior pituitary. The patients have a reduced ability to excrete diluted urine, ingested fluid is retained, and the extracellular fluid expands and becomes hypo-osmolar. The cardinal signs are hyponatraemia, serum hypoosmolality and a less than maximally diluted urine. Common symptoms include weakness, lethargy, headache, anorexia and weight gain. These symptoms may be followed by confusion, convulsions, coma and death. The early symptoms are vague and nonspecific, and they may even mimic the symptoms of the psychiatric disorder itself. For antidepressants, the risk of SIADH seems to be highest during the first weeks of treatment. For antipsychotics, the risk seems to be more spread out in time. The causative role of the drug may sometimes be difficult to estimate, as even drug-free psychiatric patients, mostly those with schizophrenia, develop SIADH on the basis of psychogenic polydipsia. Smoking is another factor associated with the development of SIADH, and the risk may also increase with age. The acute treatment of SIADH induced by a psychotropic drug includes discontinuation of the drug as well as restriction of fluid intake. In cases with significant clinical symptoms, infusion of sodium chloride is recommended. After the acute management, it is useful to evaluate the causative role of the drug by performing a water loading test and/or drug rechallenge. If continued treatment with an antidepressant or antipsychotic is indicated, a drug with a different pharmacological profile should be chosen, and the serum sodium levels should be monitored closely. If treatment with the drug that caused SIADH must be continued, concomitant treatment with demeclocycline may reduce the tendency of hyponatraemia.
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PMID:Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by psychotropic drugs. 761 32

Thirty adults with Prader-Willi syndrome (PWS) were compared with 30 adults with non-specific learning disability matched for age, sex and severity of mental retardation. Maladaptive behaviour was assessed with the Aberrant Behavior Checklist (ABC), a 58-item structured interview which rates behaviours from 0 (not a problem) to 3 (severe problem) and which yields five factors (I) irritability, agitation; (II) lethargy, withdrawal; (III) stereotypic behavior; (IV) hyperactivity, non-compliance; and (V) inappropriate speech). The PWS sample had significantly higher factor I (P < 0.001) and factor V (P < 0.05) scores. The PWS sample had mean scores above 1 for 17 ABC items; the contrast subjects had no mean scores above 1. The factor I scores for the PWS sample were similar to those of inpatients in hospital facilities for adults with mental retardation and mental illness or severely challenging behaviour. The results support previous work, and extend it by suggesting that temper tantrums, self-injury, impulsiveness, lability of mood, inactivity and repetitive speech are characteristic behaviours in PWS in adult life. Studies of the reasons for heterogeneity in behaviour are now needed.
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PMID:Maladaptive behaviour in Prader-Willi syndrome in adult life. 873 73

Dysthymia, as defined in the American Psychiatric Association and International Classification of Mental Disorders, refers to a prevalent form of subthreshold depressive pathology with gloominess, anhedonia, low drive and energy, low self-esteem and pessimistic outlook. Although comorbidity with panic, social phobic, and alcohol use disorders has been described, the most significant association is with major depressive episodes. Family history is loaded with affective, including bipolar, disorders. The latter finding explains why dysthymia, especially when onset is in childhood, can lead to hypomanic switches, both spontaneously and upon pharmacologic challenge in as many as 30%. Indeed, antidepressants from different classes -tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), selective serotonin-reuptake inhibitors (SSRIs) and, more recently, amisulpride, and spanning noradrenergic, serotonergic as well as dopaminergic mechanisms of action - have been shown to be effective against dysthymia in an average of 65% of cases. This is a promising development because social and characterologic disturbances so pervasive in dysthymia often, though not always, recede with continued pharmacotherapy beyond acute treatment. Despite symptomatic overlap of dysthymia with chronic fatigue syndrome - especially with respect to the cluster of symptoms consisting of low drive, lethargy, lassitude and poor concentration - neither the psychopathologic status, nor the pharmacologic response profile of the latter syndrome is presently understood. Chronic fatigue today is where dysthymia was two decades ago. We submit that the basic science - clinical paradigm that has proven so successful in dysthymia could, before too long, crack down the conundrum of chronic fatigue as well. At a more practical level, we raise the possibility that a subgroup within the chronic fatigue group represents a variant of dysthymia.
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PMID:Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas. 1035 46

Objective: Magnesium sulfate is the most commonly used agent for tocolysis in the management of preterm labor. Anecdotally both clinicians and patients have noted alterations in mental status of women receiving high doses of magnesium infusion, and central nervous system depression including lethargy and depression of deep tendon reflexes has been documented. Our hypothesis is that intravenous magnesium sulfate at tocolytic doses significantly affects maternal mental status.Materials and Methods: Eligibility criteria included admission or transport to University Hospital between 25 and 34 weeks gestation with an initial episode of spontaneous premature labor. Patients were consented and given an initial mental status examination prior to magnesium sulfate infusion. Those patients transported to University Hospital diagnosed with premature labor and already on magnesium were consented and given an initial mental status examination at the time of arrival. Once a therapeutic level of magnesium was documented a repeat mental status examination was performed, with a third examination performed 24 hours after the magnesium infusion has been discontinued. As a control group pregnant women hospitalized for premature rupture of the membranes not in labor had the examinations performed initially, after 24 hours of hospitalization, and again after 72 hours of hospitalization. Exclusion criteria included underlying mental illness, administration of other medications that might affect mental status, cervical dilation greater than 4 cm, clinical evidence of chorioamnionitis, or the presence of any significant abnormalities in the fetal heart rate tracing. The mental status examination consisted of the mini mental state exam, the comprehension portion of the Wechsler Adult Intelligence Scale, and the Bender-Gestalt Indicator. The results of these examinations were scored in a blinded fashion by a psychiatrist.Results: There were 22 patients in the study group and 9 patients in the control group. There were no differences in the age, gravidity, parity, or gestational age of the two groups. Out of a possible 102 points, the mean mental status scores were as follows:The mean serum magnesium level at the time of therapy was 5.1 mg/dL. The time required for response to the Wechsler test was significantly different although the scoring of the comprehension was unchanged (15.2 +/- 3.6 min vs 22.3 +/- 4.7 min, P <.05).Conclusions: This prospective blinded study reveals no differences in maternal mental status during magnesium sulfate infusion at the levels recorded in our study. There was an increase in the length of time required to answer the comprehension and judgment portion of the examination. These findings have significant clinical implications suggesting that patients on magnesium sulfate can make appropriate judgments and can, therefore, participate in clinical discussions and trials.
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PMID:Effects of magnesium sulfate tocolysis on maternal mental status. 1083 36

A review of data on HIV and depression fails to show any direct cause-and-effect relationships between the two, despite the fact that clinical depression is the most commonly seen psychiatric disorder in patients with HIV infection. Most of the HIV-positive individuals with depressive disorders were found to have a history of depression antedating their infection. Contradicting early reports of unusually high rates of depression among HIV patients, more recent studies show that depression levels are not higher for the seropositive versus the seronegative, nor do the levels increase over time or at different stages of the infection. Persons with HIV may be misdiagnosed as depressed because the somatic symptoms of the illness--fatigue, lethargy, weight loss, loss of appetite, and low libido--are also symptoms of depressive disorders. Practitioners are urged to distinguish loss of interest, per se, from loss of interest in activities due to medical problems. When HIV-infected patients are diagnosed as clinically depressed, they respond as well as seronegative patients to antidepressant medications, such as tricyclic antidepressants, serotonin reuptake inhibitors (SRRI's), and psychostimulants. Brief, focused psychotherapy can prove helpful for assisting HIV-positive patients through times of particular vulnerability: the confirmation of HIV infection, adjusting to the seropositive status, onset of physical symptoms, and a sudden decline in T-cell counts.
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PMID:Depressive disorder and HIV disease: an uncommon association. 1136 50


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