Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, with the increase in elderly population, we have had more opportunities to administer neuroleptics to elderly patients for hallucinatory delusional state, delirium, psychomotor excitement, wandering etc. However, little is known about the characteristics of the neuroleptic malignant syndrome (NMS) in elderly patients, which is the most serious side effect of neuroleptics. In this paper, we present the clinical course of five NMS patients in the presenium and senium. Case 1 was 72-year-old male who was diagnosed as having dementia of Alzheimer's type (with late onset). He showed nocturnal wandering, insomnia, and irritability. Tiapride 60 mg per day had been administered previously. Just after the addition of oxypertine 10 mg per day, NMS occurred, and he died of pneumonia a week later. Case 2 was 75-year-old male who was diagnosed as having vascular dementia. He showed insomnia, hyperactivity and wandering. He had been given levomepromazine (LPZ) 10 mg per day over a long period of time. At first, he had daily episodic fever, however, serum CPK levels did not increase at that time. A month later, all the symptoms of NMS appeared and then the patient's condition suddenly deteriorated and he died three days later. Case 3 was a 64-year-old male who was diagnosed as having dementia of Alzheimer's type (with early onset). He showed insomnia, irritability and violence. Tiapride 50-125 mg per day was administered along with oxypertine 50-115 mg per day. Almost two months later, NMS occurred. He had daily episodic fever at first, extrapyramidal symptoms and autonomic instabilities gradually increased. Soon after symptoms of NMS were completed. In this case, NMS seemed to be induced by bacterial pneumonia after long term administration of LPZ 5 mg per day. Case 4 was a 75-year-old female who was diagnosed as having dementia of Alzheimer's type (with late onset). She showed hallucinatory delusional state. Although she had autonomic instabilities just after adminstration of haloperidol 1-2 mg per day, NMS itself occurred after discontinuing the neuroleptic. Case 5 was a 61-year-old female who was diagnosed as having schizophrenia at the age of forty. She was given various neuroleptics over a period of time. The neuroimaging in SPECT showed her cerebral cortex was generally hypoactive. She had a tendency to have autonomic instabilities after the administration of relatively high potential neuroleptics. Risperidone 3-6 mg per day was administered, and almost a month later, autonomic instabilities increased and she was diagnosed as having NMS. All the patients would be able to have brain dysfunction, which suggested that such patients may be liable to NMS. In our patients, NMS occurred after the additional administration of oxypertine 10 mg per day or after long time administration of LPZ 5 mg per day. It was suggested that NMS could occur after the administration of low dose and relatively low potential neuroleptics in elderly patients. Our 3 of 5 patients showed the delayed type of NMS, which might be relatively more frequent in senior and presenior patients than in younger patients. In case 3, NMS was induced by the somatic disease (bacterial pneumonia), however in other cases, NMS was not always induced by somatic disease. Our 4 of 5 patients experienced some of the symptoms of NMS--episodic fever, extrapyramidal symptoms and autonomic instabilities--before the onset of NMS. Such symptoms may be "pre-steps" to NMS. Once NMS occurred, the patient's systemic condition tended to deteriorate acutely. Due to the fact that our 2 of 5 patients died, it was suggested that the prognosis of the NMS patients in presenium and senium tends to be much worse. It is important to find the "pre-steps" to NMS and treat them as soon as possible for better prognosis.
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PMID:[A study of neuroleptic malignant syndrome in the presenium and senium]. 974 53

A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165/90 and 130/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU/L), aspartate aminotransferase (134 IU/L), alanine aminotransferase (78 IU/L), and BUN (27.9 mg/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression.
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PMID:Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam. 1672 68

Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme. The second study consisted of 2 phases. In the initial phase, subjects were administered SD PBO (N = 2/period) or VBZ (N = 6/period; 75, 100, 125 or 150 mg) with sequential escalation. In the second phase, subjects received PBO, or 50 or 100 mg VBZ (N = 4:8:8) QD for 8 days (Cohort 1) or PBO or 50 mg VBZ (N = 6:6) QD for 8 days (Cohort 2). For both studies, plasma concentrations of VBZ and its active metabolite, NBI-98782, were determined. Safety was assessed throughout the studies. PK parameters were determined using noncompartmental methods. In both studies, VBZ was rapidly absorbed with peak concentrations typically observed within 1.5 hours. Peak NBI-98782 concentrations were typically observed at 4.0 to 9.0 hours. Terminal elimination half-life for both VBZ and NBI-98782 was ~20 hours. Across the 1 to 150 mg SD range evaluated across the studies, VBZ and NBI-98782 Cmax and AUC increased dose-proportionally from 50 to 150 mg and more than dose-proportionally from 1 to 50 mg. QD VBZ and NBI-98782 Cmax and AUC parameters were also dose-proportional between the 50 and 100 mg doses. Steady-state for both analytes appeared to be achieved by Day 8. The accumulation index was ~1.5 for VBZ and ~2.5 for NBI-98782. Peak to trough fluctuation was approximately 250% for VBZ and 70% for NBI-98782. Across both studies, NBI-98782 exposure was approximately 20%-30% that of VBZ based on molar ratios. In the first study, the maximum-tolerated dose was not achieved; headache (2 events) was the only treatment-emergent adverse event (TEAE) reported by more than one subject. In the second study, fatigue (4 events) was the only TEAE reported by more than one subject following SD VBZ. Following QD VBZ, the TEAEs of fatigue, insomnia, disturbance in attention, and nervousness were dose-dependent; the latter three TEAEs were considered dose-limiting. Subject withdrawals due to TEAEs were 1 each for PBO and 50 mg VBZ QD, and 3 for 100 mg VBZ QD. Clinically relevant effects on laboratory parameters, vital signs or ECGs were limited to increased CPK (SD: 1 each for 5 mg VBZ and PBO), ALT (QD: 1 each for 50 and 100 mg VBZ and PBO), and triglycerides (QD: 1 each for 50 mg VBZ and PBO). VBZ has an acceptable safety profile and predictable pharmacokinetics that result in stable concentrations of active compounds with low peak-to-trough fluctuation following once-daily dosing.
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PMID:Single Dose and Repeat Once-Daily Dose Safety, Tolerability and Pharmacokinetics of Valbenazine in Healthy Male Subjects. 2883 39