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)

Buspirone was compared to alprazolam and lorazepam in the treatment of generalized anxiety disorder in a 4-week, double-blind study of 60 patients. All three medications were effective and similar in producing significant reductions in anxiety as assessed by standardized anxiety rating scales and by global evaluations of patients by physicians. There were significant differences in drowsiness, lethargy, and/or fatigue: fewer patients in the buspirone group than in the alprazolam group (16% vs. 60%, respectively; p less than .01) or the lorazepam group (16% vs. 65%, respectively; p less than .0003) experienced these undesirable side effects. This demonstration of similar effectiveness and superior safety would favor buspirone in the treatment of generalized anxiety disorder.
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PMID:Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients: a double-blind study. 287 28

The pharmacokinetics of a new 10 mg sublingual tablet formulation of temazepam and those of a currently marketed 10 mg oral capsule formulation were evaluated in a group of ten healthy volunteers. No significant differences were observed between the two formulations with respect to any of the pharmacokinetic parameters assessed. Lethargy and somnolence were reported on both capsule and tablet by several subjects at a time which corresponded with the maximum concentration of drug in plasma. The data indicate that the sublingual tablet and orally administered capsule have a similar pharmacokinetic and pharmacodynamic profile.
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PMID:Pharmacokinetics of a new sublingual formulation of temazepam. 290 71

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.
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PMID:[Phase I-II study of recombinant interferon gamma]. 298 59

A double-blind, crossover, placebo-controlled study was carried out in 10 healthy male volunteers to investigate the effects of subcutaneously administered single doses of 4 and 8 mg morphine and 2.5 and 5 mg of a new centrally acting analgesic with a benzomorphane structure. After an adaptation session, each subject received all five treatments in a random sequence at intervals of 1 week. Quantified EEG, cardiovascular and behavioral parameters, quantitative respiratory measurements, body temperature, symptom reports, pain threshold estimates, and blood drug assays were used to assess the effects of the drugs. The measurement battery was completed before injection and after 30, 60, 120, 240 and 360 min. In addition, EEG, blood samples and respiratory signals were also taken during/after the first 5, 10, 15, 20 and 25 min. As the new compound did not show any obvious advantages over morphine, only the results with the latter substance are reported here. As the main effects of morphine on the EEG a dose-dependent slowing and monorhythmization of alpha and an increase of the average frequency of fast beta activity were observed. Slow EEG waves tended to decrease. Heart rate and body temperature decreased, whereas there was no discernible effect on blood pressure. Subjects reported feelings of drowsiness, muzziness, lethargy and mental slowness. The pain threshold increased. All these effects had a maximum between min 120 and 240, although the highest blood levels of the parent drug were measured 10-25 min after drug administration. An explanation for this delay might be that the pharmacological effects are due not to free morphine but to one of its metabolites.
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PMID:Effect of morphine on the electroencephalogram and other physiological and other physiological and behavioral parameters. 307 22

Pipequaline (PK 8165) is a putative mixed agonist/antagonist at benzodiazepine receptors. The effects of pipequaline and diazepam on memory were assessed in 12 normal volunteers. Diazepam 10 mg or placebo was added to two doses of pipequaline, 50 and 150 mg, or to placebo in a double-blind crossover design. Diazepam produced impairments of episodic memory. In contrast, the effects of pipequaline were minor. Addition diazepam to pipequaline increased drowsiness and general lethargy, with a less marked effect occurring for the higher dose of pipequaline alone. Pipequaline did not antagonise any of the effects of diazepam.
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PMID:The effects on memory of pipequaline, alone or in combination with diazepam. 313 26

This double-blind, three-way crossover study measured the influence of beta-blocker treatment on drowsiness and mental test performance in older hypertensive patients and determined if lipophilicity was a determinant of these effects. Twenty-seven hypertensive patients (mean age, 63 +/- 3 years) were studied. Patients received two weeks each of daily treatment with placebo, 100 mg of atenolol, or 150 mg of metoprolol tartrate and were evaluated on the 14th day of each treatment period, after which their next treatment period began. Mental performance was measured using Trails-A maze testing. Drowsiness was measured subjectively using a visual analogue scale, and objectively using critical fusion-frequency threshold testing. Blood pressure control was equivalent and clinically adequate in all subjects. Steady-state levels of metoprolol tartrate (235.7 +/- 46 ng/mL) and atenolol (453.6 +/- 56 ng/nL) achieved were those expected to produce similar beta-blockade. Mental performance as measured by Trials-A testing showed better scores during beta-blocker treatment compared with placebo. Trails-A scores improved as patients went from placebo to metoprolol treatment, but did not change as patients went from placebo to atenolol treatment. Critical fusion-frequency threshold measurements were lower following administration of both drugs than following that of placebo, but subjectively there was no difference in feelings of lethargy between either beta-blocker and placebo. These data show greater improvement in mental testing performance to be associated with metoprolol treatment, but neither produced more lethargy than placebo in elderly patients.
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PMID:The effect of beta-blockers on mental performance on older hypertensive patients. 271 20

Trazodone demonstrates comparable efficacy with the tricyclic antidepressant agents (TCAs) but produces fewer of the untoward side effects associated with these drugs. All of the TCAs are potentially lethal when taken in overdose; they cause serious cardiovascular side effects; produce anticholinergic effects, which often are severe enough to result in discontinuation of medication; and impair cognition, especially in elderly patients. In contrast, trazodone is relatively safe when taken in overdose; no deaths have been reported to the manufacturer when trazodone was the only agent taken. Trazodone produces fewer and milder cardiovascular disturbances and anticholinergic effects than TCAs. If anticholinergic side effects do occur then they are rarely bothersome enough to result in discontinuation of therapy. In addition, cognitive skills, even in elderly patients, are less impaired in patients receiving trazodone therapy than in patients receiving TCA drugs. Although trazodone therapy has been associated with lethargy, dizziness, drowsiness, and confusion in some patients, symptoms have been mild and can be further minimized by administering the drug either after meals or once daily at bedtime.
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PMID:The greater safety of trazodone over tricyclic antidepressant agents: 5-year experience in the United States. 332 Nov 31

15 patients aged between 24 and 66 years with 10 different malignant tumor diseases were treated with a recombinant human tumor necrosis factor preparation PAC-4D in a phase-I trial. The starting dose was 10(5) U PAC-4D as an intravenous short infusion. The maximally tolerable dose is around 18 X 10(5) U/m2. As the main clinical side effects were observed: fever, chills, hypertension with subsequent hypotension, lethargy, transient somnolence, headache, neurological deficiency symptoms, nausea and vomiting. Important laboratory-chemical parameters were the increase in transaminases and, in higher dose levels, leukocytosis with the left shift and lymphopenia in the differential blood picture. As dose-limiting toxicity are estimated hypotension, and neurological side effects and hepatotoxicity. In one female patient who received 27 X 10(5) U PAC-4D there appeared pronounced, histologically verified necroses in the metastases of a malignant fibrous histiocytoma.
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PMID:Human pharmacological investigation of a human recombinant tumor necrosis factor preparation (PAC-4D) a phase-I trial. 337 52

The National Cancer Institute of Canada (NCIC) Clinical Trials Group has carried out a phase II study of acivicin given as a 72-hour continuous infusion in previously untreated patients with measurable metastatic colorectal carcinoma. Toxicity in 24 patients was mild to moderate and consisted primarily of GI symptoms such as nausea, vomiting, diarrhea or CNS changes including drowsiness, lethargy, dizziness. No responses were seen in 23 evaluable patients. We did not find acivicin given as described to be effective in colorectal carcinoma.
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PMID:Phase II study of acivicin as a 72-hr continuous infusion in patients with untreated colorectal cancer. A National Cancer Institute of Canada Clinical Trials Group Study. 343 43

Despite the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs), the current number of reported cases of poisoning is small. However, with the introduction of 'over-the-counter' preparations of NSAIDs in some countries (e.g. ibuprofen in the UK and USA) an increased incidence of acute poisoning from this group of drugs can be expected. Conventionally, NSAIDs are divided into the following groups based on their chemical structure: arylpropionic acids, indole and indene acetic acids, heteroarylacetic acids, fenamates, phenylacetic acids, pyrazolones and oxicams. Unless NSAIDs are ingested in substantial overdose, acute poisoning with these agents does not usually result in significant morbidity or mortality. In most cases the clinical features are mild and confined to the gastrointestinal and central nervous systems, though acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse and cardiac arrest may complicate severe poisoning. Arylpropionic acid derivatives were thought initially to have a low order of toxicity in overdose but, in addition to anticipated gastrointestinal symptoms, headache, tinnitus, hyperventilation, sinus tachycardia, hypoprothrombinaemia, haematuria, proteinuria and acute renal failure have been described. In addition, drowsiness, coma, nystagmus, diplopia, hypothermia, hypotension, respiratory depression and cardiac arrest have been reported in severe cases of poisoning. Oxyphenbutazone and phenylbutazone are considerably more toxic in overdose. Complications of severe poisoning include coma, convulsions, hepatic dysfunction, acute renal failure, sodium and water retention, haematuria, cardiovascular collapse, respiratory alkalosis, metabolic acidosis, hypoprothrombinaemia and thrombocytopenia. In contrast, indomethacin appears to be much less toxic. In addition to gastrointestinal symptoms, indomethacin taken in overdose induces headache, tinnitus, dizziness, lethargy, drowsiness, confusion, disorientation and restlessness. Only 1 case of acute sulindac poisoning has been reported in the literature. A 16-year-old boy was admitted with hypokalaemia (2.2 mmol/L), transient granulocytosis and 'scanty' haematemesis after ingesting 12 g sulindac. No case of acute tolmetin poisoning have been reported. The fenamates (flufenamic acid, meclofenamic acid, mefenamic acid, tolfenamic acid) are, with the exception of mefenamic acid, not as widely prescribed as other groups of NSAIDs. In overdose, mefenamic acid may result in nausea, vomiting, diarrhoea, muscle twitching, convulsions and coma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management. 353 13


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