Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olanzapine is a recently introduced atypical neuroleptic agent for which little information is available on its use in children. Open clinical trials of olanzapine treatment were conducted on five hospitalized children (ages 6 to 11 years) with varying diagnoses including bipolar disorder, psychosis not otherwise specified, schizophrenia, and attention-deficit/ hyperactivity disorder. Each patient had failed previous psychotropic medication trials, with a mean of four prior trials. The mean length of olanzapine treatment was 32 days (range, 2 to 7 weeks), and mean daily dose was 7.5 mg/day (range, 2.5 to 1.0 mg/day) or 0.22 mg/kg/day (range, 0.12 to 0.29 mg/kg/day). All children experienced adverse effects, including sedation (N = 3), weight gain of up to 16 pounds (N = 3), and akathisia (N = 2). Three patients showed some clinical improvement, but olanzapine treatment was discontinued in all five children within the first 6 weeks of treatment because of adverse effects or lack of clinically significant therapeutic response, although higher (or lower) doses, slower titration of dosage, or a longer duration of treatment might have produced more favorable results. Psychotic symptoms did not respond in the two patients with evidence of overt hallucinations and paranoid ideation. Improvement was observed in sleep in all five patients and in control of aggression in three. Before controlled trials of olanzapine in children are undertaken, further exploration of dose range and increased duration of treatment on an open basis are warranted. Until more encouraging data are available, clinicians should be cautious and conservative in their predictions about the potential value of olanzapine in treating preadolescent psychiatric disorders.
 ...
PMID:Open-label olanzapine treatment in five preadolescent children. 973 76

Olanzapine is a newly developed atypical neuroleptic with a marked affinity to the 5-HT2, D2 and D4 dopamine receptors. Like other atypical neuroleptics olanzapine is considered to show a reduced prevalence of extrapyramidal side effects when compared to classical neuroleptic drugs. We report on three patients with acute schizophrenia, who developed severe akathisia during treatment with olanzapine (20-25 mg/d). In two of these cases akathisia resolved after withdrawal of olanzapine and substitution by a classical or an atypical neuroleptic agent, respectively. In one of these patients olanzapine was well tolerated when reintroduced in combination with lorazepam after complete remission of akathisia. In the third patient akathisia was sufficiently controlled by dose reduction. Akathisia is generally considered to result from D2 dopamine receptor antagonism. In the case of atypical neuroleptics such as olanzapine a low but still considerable D2 dopamine receptor occupancy may be compensated by the 5-HT2 antagonism. However, this mechanism may fail under certain circumstances, in particular if D2 dopamine antagonism exceeds a certain threshold. One should therefore be aware of possible extrapyramidal side effects with olanzapine that are reduced compared to classical neuroleptic drugs but not completely eliminated.
 ...
PMID:Severe akathisia during olanzapine treatment of acute schizophrenia. 975 50

Olanzapine is a relatively new antipsychotic agent which appears to be effective in the treatment of both the positive and negative symptoms of schizophrenia. Reported here is the case of a patient who developed symptoms of mania secondary to treatment with olanzapine. Physicians prescribing olanzapine should be aware of this potential complication.
 ...
PMID:Olanzapine-induced mania. 982 37

Olanzapine, a new antipsychotic agent, was approved by the U.S. Food and Drug Administration in 1996 for use in the treatment of schizophrenia. It is structurally similar to clozapine, has a low incidence of extrapyramidal effects, and is effective in treating both the positive and negative symptoms of schizophrenia. This paper describes the determination of olanzapine in biological specimens obtained from the autopsy of a 35-year-old white male found dead in bed at a psychiatric facility. In the months prior to his death, the deceased was prescribed multiple medications, including olanzapine. Olanzapine was identified qualitatively by full scan gas chromatography-mass spectrometry, with quantitative analysis performed by liquid-liquid extraction followed by dual-column gas chromatography. The following concentrations were determined in the specimens analyzed: heart blood, 550 ng/mL; bile, 6346 ng/mL; and gastric contents, 157 ng/mL. Vitreous humor, cerebrospinal fluid, and urine specimens were negative. Although steady-state plasma concentrations of 10-25 ng/mL olanzapine have been reported, effective levels are known to be highly variable and a plasma concentration of 300 ng/mL has been tolerated without adverse effects. Based upon the autopsy, toxicological findings, and case investigation, the cause of death was determined to be intramyocardial arteriosclerosis with severe stenosis of the nodal artery due to hypertensive cardiovascular disease, and the manner was natural.
 ...
PMID:Determination of olanzapine in a postmortem case. 984 13

Olanzapine, an atypical antipsychotic, has a broad receptor binding profile, which may account for its pharmacological effects in schizophrenia. In vitro receptor binding studies showed a high affinity for dopamine D2, D3, and D4 receptors; all 5-HT2 receptor subtypes and the 5-HT6 receptor; muscarinic receptors, especially the M1 subtype: and alpha 1-adrenergic receptors. In vivo studies showed that olanzapine had potent activity at D2 and 5-HT2A receptors, but much less activity at D1 and muscarinic receptors, and that it inhibited dopaminergic neurons in the A10 but not the A9 tract, suggesting that this agent will not cause extrapyramidal side-effects (EPS). Microdialysis studies showed that olanzapine increased the extracellular levels of norepinephrine and dopamine, but not 5-HT, in the prefrontal cortex, and increased extracellular dopamine levels in the neostriatum and nucleus accumbens, areas of the brain associated with schizophrenia. Studies of gene expression showed that olanzapine 10 mg/kg also increased Fos expression in the prefrontal cortex, the dorsolateral striatum, and the nucleus accumbens. These findings are consistent with the effectiveness of olanzapine on both negative and positive symptoms and suggest that, with careful dosing, olanzapine should not cause EPS.
 ...
PMID:Olanzapine: a basic science update. 1021 Nov 40

Olanzapine possesses a broad pharmacological profile, interacting with a range of different neurotransmitter receptors. Although its affinity for muscarinic receptors is relatively greater than for dopamine receptors, on schedule-controlled behaviour olanzapine displays a profile resembling a dopamine antagonist. Likewise, in a test of cognitive function, olanzapine does not produce anticholinergic-like deficits. In drug discrimination assays, olanzapine substitutes for clozapine in clozapine-trained animals and clozapine generalises to olanzapine in olanzapine-trained animals. Olanzapine also reverses the behavioural deficits produced by inhibiting N-methyl-D-aspartate receptor glutamatergic transmission. This profile suggests that olanzapine will be effective against both positive and negative symptoms of schizophrenia while producing minimal extrapyramidal side-effects.
 ...
PMID:Olanzapine: preclinical pharmacology and recent findings. 1021 Nov 41

Olanzapine, a new atypical antipsychotic drug, has been prescribed in the treatment of schizophrenia and psychotic mood disorders for approximately 2.3 million patients worldwide. Considering the increase in olanzapine prescriptions and the increased risk of suicide in this patient population, the number of reported cases of olanzapine overdose may be expected to increase. This report describes the clinical course and serum concentrations in a patient who consumed an olanzapine overdose (800 mg). Profound central nervous system depression and tachycardia without arrhythmia occurred within 2 hours after the ingestion. Additional clinical findings (ie, fever, mutism, agitation, dystonia, akathisia, elevated creatine kinase, and increased leukocyte count) were similar to those of neuroleptic malignant syndrome. After intubation, gut decontamination, and supportive care, the patient recovered and was discharged.
 ...
PMID:Olanzapine overdose with serum concentrations. 1042 35

This article will briefly familiarize the reader with the positive and negative signs and with the symptoms of Schizophrenia. After describing these signs and symptoms, the atypical anti-psychotic medications of Risperidone, Olanzapine and Clozapine will be reviewed as to their pharmacodynamics, dosages, and side effects in treating of these sign and symptoms. Within the scope of practice for advance practice nurses, the care being rendered and the implementation of those atypical drugs will be described. Thanks to their educational and clinical background, the advanced practice nurses find themselves in a unique set of circumstances to positively contribute in the treatment and maintenance of Schizophrenia.
 ...
PMID:Schizophrenia treatment: the use of atypical drugs--risperdal, zyperexa, and clozaril. 1045 1

The treatment of schizophrenic patients who fail adequate trials of typical neuroleptics is a major challenge. For these patients, the availability of atypical antipsychotics is a useful therapeutic advance. Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenia, particularly its negative symptoms, with a substantially more favorable safety profile than conventional antipsychotic agents (e.g., haloperidol). However, little information on the clinical effects of olanzapine is available in Japan. This article provides information on the efficacy of olanzapine for various symptoms of schizophrenic patients and drug safety. Olanzapine is significantly superior to haloperidol in positive, negative, and depressive symptoms of patients, and for tardive dyskinesia and extrapyramidal symptoms. Significantly greater improvement in avolition-apathy is achieved with olanzapine as compared to risperidone. These advantages are related to high affinity at the 5-HT2 binding site, no association with an alteration in dopamine A9 firing rates, and lower D2 striatal receptor blockade of olanzapine. Treatment with 10 mg/day olanzapine is more appropriate for positive symptoms, and 12.5-17.5 mg/day olanzapine is more effective for negative symptoms. Patients will need help adapting to a new level of functioning after a successful switch to olanzapine, and overcoming the disappointment that eventually occurs when the limitations of olanzapine become apparent.
 ...
PMID:[Clinical efficacy of olanzapine]. 1049 84

Multicentre trials in patients with schizophrenia confirm that olanzapine is a novel antipsychotic agent with broad efficacy, eliciting a response in both the positive and negative symptoms of schizophrenia. Compared with traditional antipsychotic agents, olanzapine causes a lower incidence of extrapyramidal symptoms and minimal perturbation of prolactin levels. Generally, olanzapine is well tolerated. The pharmacokinetics of olanzapine are linear and dose-proportional within the approved dosage range. Its mean half-life in healthy individuals was 33 hours, ranging from 21 to 54 hours. The mean apparent plasma clearance was 26 L/h, ranging from 12 to 47 L/h. Smokers and men have a higher clearance of olanzapine than women and nonsmokers. After administering [14C]olanzapine, approximately 60% of the radioactivity was excreted in urine and 30% in faeces. Olanzapine is predominantly bound to albumin (90%) and alpha 1-acid glycoprotein (77%). Olanzapine is metabolised to its 10- and 4'-N-glucuronides, 4'-N-desmethylolanzapine [cytochrome P450 (CYP) 1A2] and olanzapine N-oxide (flavin mono-oxygenase 3). Metabolism to 2-hydroxymethylolanzapine via CYP2D6 is a minor pathway. The 10-N-glucuronide is the most abundant metabolite, but formation of 4'-N-desmethylolanzapine is correlated with the clearance of olanzapine. Olanzapine does not inhibit CYP isozymes. No clinically significant metabolic interactions were found between olanzapine and diazepam, alcohol (ethanol), imipramine, R/S-warfarin, aminophylline, biperiden, lithium or fluoxetine. Fluvoxamine, an inhibitor of CYP1A2, increases plasma concentrations of olanzapine; inducers of CYP1A2, including tobacco smoke and carbamazepine, decrease olanzapine concentrations. Orthostatic changes were observed when olanzapine and diazepam or alcohol were coadministered. Pharmacodynamic interactions occurred between olanzapine and alcohol, and olanzapine and imipramine, implying that patients should avoid operating hazardous equipment or driving an automobile while experiencing the short term effects of the combinations. Individual factors with the largest impact on olanzapine pharmacokinetics are gender and smoking status. The plasma clearance of olanzapine generally varies over a 4-fold range, but the variability in the clearance and concentration of olanzapine does not appear to be associated with the severity or duration of adverse effects or the degree of efficacy. Thus, dosage adjustments appear unnecessary for these individual factors. However, dosage modification should be considered for patients characterised by a combination of factors associated with decreased oxidative metabolism, for example, debilitated or elderly women who are nonsmokers.
 ...
PMID:Olanzapine. Pharmacokinetic and pharmacodynamic profile. 1051 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>