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)

Studies of depression associated with oral contraceptive use present conflicting results. Individual susceptibility may affect psychiatric symptoms more than biochemical composition of the pill. In the authors' study 40 women without previous histories of depression were assigned to 4 regimens: 1) mestranol 80 mcg, norethisterone 1.0 mg; 2) pill 1 and pyridoxine; 3) mestranol 5 mcg, norethisterone 1.0 mg; and 4) pill 3 and pyridoxine. Alcohol and other chemicals were avoided. The 40 subjects completed self-reporting ratings on depression and a libido rating. 24 hour urine samples were collected on day 14 and 21 of the menstrual cycle. A brief psychiatric interview was conducted monthly. Adrenaline, noradrenaline, and 5 HIAA were measured throughout the year long study. 10 women completed 3 cycles. 20 of 10 complained of lethargy, loss of libido, irritability, and moodiness. The study concludes that biochemical and pharmacological effects affect a minority of women. A psychologic and negative placebogenic effect is possible. Depending on the composition of the contraceptive, a differential effect may occur. Sequential pills caused less depression than combination types.
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PMID:Oral contraceptives and depression. 44 Dec 35

The functions of the central monoamines Norepinephrine (NE) and Serotonin (5HT) can be clarified by the study of behaviors of rats administered selective monoamine toxins. In his home environment the low NE rat has drive deficits and is lethargic, tending to remain in his burrow, but in novel environments this animal acts less frightened than Controls. The low 5HT rat is conversely active and exploratory in familiar environments but frightened in novel environments. These two animals model aspects of depression and anxiety, respectively. 5HT can be thought of as placing the brain into a state of consciousness appropriate for an animal in his nest (i.e., 5HT neurons act as relaxers), and as involved in a type of positive affect related to security, whereas NE neurons are dominant when an animal is vigilant, foraging out in the environment and are involved in a type of positive affect related to goal-directed approach arousal. Monoamine toxins may be produced when the behaviors elicited by these central neuronal systems are negatively reinforced (extinguished).
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PMID:Behavior and the balance between norepinephrine and serotonin. 123 10

The calcium antagonists are a heterogeneous class of drugs which block the inward movement of calcium into cells through 'slow channels' from extracellular sites. By inhibiting phase 0 depolarisation in cardiac pacemaker cells and phase 2 plateau in myocardium, and by depressing calcium ion flux in smooth muscle cells of blood vessels, these agents may exert profound effects on the cardiovascular system, particularly in susceptible individuals or in overdose. Sinus node depression, impaired atrioventricular (AV) conduction, depressed myocardial contractility, and peripheral vasodilatation may result. Pharmacokinetic features of calcium antagonists include rapid and complete absorption from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bioavailability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. Impaired renal function does not affect pharmacokinetics. Verapamil is the most potent inhibitor of cardiac conduction and contractility, with diltiazem also showing such effects. Nifedipine is the most potent vasodilator, but only occasionally impairs the sinus node or AV conduction. Significant pharmacodynamic effects are common during combination therapy with calcium antagonists, especially verapamil and beta-blockers. Verapamil may significantly elevate serum digoxin concentrations and may exert additive negative effects on chronotropism and dromotropism when this combination is used. Overdoses of calcium entry blockers are becoming more frequent and reflect an extension of the known pharmacodynamic profile of these agents. Typical features include confusion or lethargy, hypotension, sinus node depression and cardiac conduction defects. Onset of symptoms may be delayed if a sustained release preparation is ingested. Management of calcium antagonist overdose includes gut decontamination with lavage and activated charcoal. All symptomatic patients and patients with a history of ingesting a sustained release preparation should be admitted for ECG monitoring. If bradycardia and/or conduction defects contribute to hypotension, atropine or isoprenaline (isoproterenol) may accelerate the ventricular rate. Transvenous pacing may be required. Depressed myocardial contractility usually responds well to calcium chloride or calcium gluconate administration, but further inotropic support may be required. Peripheral vasodilation should be managed with intravenous fluids and a pressor agent such as dopamine or norepinephrine (noradrenaline).
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PMID:Poisoning due to calcium antagonists. Experience with verapamil, diltiazem and nifedipine. 179 22

We report a 12 month double-blind randomized crossover trial of fenfluramine in 20 children with the syndrome of autism. On active drug most of the children lost weight and blood serotonin levels fell by an average of 60%. There was a fall in urinary dopamine (DA) and noradrenaline (NA) levels and increased excretion of homovanillic acid (HVA). Some of the children showed improvement in tests of cognitive and language function, although the results did not achieve overall statistical significance. Event-related brain potentials (ERPs) were obtained in seven subjects on an auditory choice reaction time task. Side effects of the drug included irritability and lethargy. Fenfluramine may have a limited place in the management of some patients with autistic disorder.
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PMID:A controlled crossover trial of fenfluramine in autism. 219 54

1. 6-Hydroxydopamine (200 mug injected intraventricularly) caused depletion of noradrenaline from all regions of rat brain within 2 h after injection but depletion of dopamine in the brain was observed only from 2 days after injection. Both catecholamines remained depleted for more than 32 days.2. Rats treated with intraventricular 6-hydroxydopamine were sedated and lethargic, with reduced spontaneous and exploratory activity, for periods of up to 8 days after injection. Conditioned avoidance responding was abolished or reduced for a similar period.3. Intraventricular 6-hydroxydopamine caused a prolonged reduction in the amount of labelled catecholamines in store 4 h following an intraventricular injection of (3)H-dopamine. During the first 6 h after 6-hydroxydopamine injection, there was a marked increase in neutral and acid metabolites from the labelled catecholamines.4. A comparison of the behavioural and biochemical effects of intraventricular 6-hydroxydopamine and reserpine suggests that both drugs affect catecholamine storage mechanisms but by different mechanisms. It was not possible from these experiments to correlate behavioural changes with either catecholamine storage or metabolism.
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PMID:Effects of intraventricular 2,4,5-trihydroxyphenylethylamine (6-hydroxydopamine) on rat behaviour and brain catecholamine metabolism. 549 79

The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion. 637 96

Unilateral brain ischemia was induced in the rat by injecting radioactive microspheres into the left internal carotid artery. The microspheres were mainly distributed in the left cerebral hemisphere which contained 8 to 10 times more microspheres than the contralateral hemisphere. Embolization caused dopamine (DA) and noradrenaline (NA) depletion only in the left hemisphere. NA levels were already reduced 2 hours after injury while DA was still unaltered after 6 hours. A 30--40% depletion was observed for the two amines after 24 hours. Catecholamine turnover was estimated by measuring the amine depletion after synthesis inhibition with alpha-methyl-p-tyrosine. During the first 2 hours following embolization, DA and NA depletions were slightly increased only in the left hemisphere, indicating an increase in catecholamine efflux. At times 24 hours, an important retardation in amine disappearance after synthesis inhibition was found for DA and NA in the left hemisphere and to a lesser extent for DA in the right hemisphere, suggesting a reduction of the physiological activity of catecholaminergic neurons. These biochemical alterations can be related to the post-stroke behavioural changes of the embolized animals which exhibited an initially increased motor activity followed by a lethargic state.
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PMID:Catecholamine levels and turnover during brain ischemia in the rat. 740 Aug 6

Serotonin syndrome (SS) is a potentially fatal complication of the combined use of agents that enhance serotonin activity. Bupropion inhibits noradrenaline and dopamine reuptake with milder effects on serotonergic activity. Although regarded as a potential causative agent for SS, no cases have been reported in the medical literature. A 62-year-old woman treated with therapeutic dosages of bupropion and sertraline for depression for the previous 3 weeks presented with upper extremity myoclonic jerks, clumsiness, and gait difficulties with fluctuating symptoms of confusion, forgetfulness, and the alternation of agitation and lethargy. Symptoms were interpreted as an aggravation of depression and venlafaxine was added. The clinical picture progressed to alteration of consciousness and dysautonomia. After admission, medications were discontinued and she was started on cyproheptadine and clonazepam with gradual improvement and complete resolution of symptoms. This is a rare report of SS related to the association of bupropion and selective serotonin reuptake inhibitors (SSRIs). It also illustrates the potential for misinterpretation of the earliest manifestations of SS as signs of aggravation of the patient's underlying condition. The role of bupropion in SS is possibly related to its well-established specific inhibition of the cytochrome P450 2D6 pathway, increasing blood levels of SSRIs and tricyclic antidepressants.
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PMID:Serotonin syndrome induced by a combination of bupropion and SSRIs. 1560 2

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.
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PMID:Neuropsychiatric adverse effects of interferon-alpha: recognition and management. 1569 25

The original central fatigue hypothesis suggested that an exercise-induced increase in extracellular serotonin concentrations in several brain regions contributed to the development of fatigue during prolonged exercise. Serotonin has been linked to fatigue because of its well known effects on sleep, lethargy and drowsiness and loss of motivation. Several nutritional and pharmacological studies have attempted to manipulate central serotonergic activity during exercise, but this work has yet to provide robust evidence for a significant role of serotonin in the fatigue process. However, it is important to note that brain function is not determined by a single neurotransmitter system and the interaction between brain serotonin and dopamine during prolonged exercise has also been explored as having a regulative role in the development of fatigue. This revised central fatigue hypothesis suggests that an increase in central ratio of serotonin to dopamine is associated with feelings of tiredness and lethargy, accelerating the onset of fatigue, whereas a low ratio favours improved performance through the maintenance of motivation and arousal. Convincing evidence for a role of dopamine in the development of fatigue comes from work investigating the physiological responses to amphetamine use, but other strategies to manipulate central catecholamines have yet to influence exercise capacity during exercise in temperate conditions. Recent findings have, however, provided support for a significant role of dopamine and noradrenaline (norepinephrine) in performance during exercise in the heat. As serotonergic and catecholaminergic projections innervate areas of the hypothalamus, the thermoregulatory centre, a change in the activity of these neurons may be expected to contribute to the control of body temperature whilst at rest and during exercise. Fatigue during prolonged exercise clearly is influenced by a complex interaction between peripheral and central factors.
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PMID:Central fatigue: the serotonin hypothesis and beyond. 1700 50


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