Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antipsychotic medication has been enormously helpful in the treatment of psychotic symptoms during the past several decades. Unfortunately, several important side effects that can cause significant morbidity and mortality. The two most common are abnormal involuntary movements (tardive dyskinesia) and weight gain progressing through diabetes to metabolic syndrome. A more rare and life-threatening adverse effect is clozapine-induced agranulocytosis (CIA), which has been linked to clozapine use. Clozapine itself has a unique position among antipsychotic medications, representing the treatment of choice in refractory schizophrenia. Unfortunately, the potential risk of agranulocytosis, albeit small, prevents the widespread use of clozapine. Very few genetic determinants have been clearly associated with CIA due to small sample sizes and lack of replication in subsequent studies. The HLA system has been the main hypothesized region of interest in the study of CIA, and several gene variants in this region have been implicated, particularly variants of the HLA-DQB1 locus. A preliminary genome-wide association study has been conducted on a small sample for CIA, and a signal from the HLA region was noted. However, efforts to identify key gene mechanisms that will be useful in predicting antipsychotic side effects in the clinical setting have not been fully successful, and further studies with larger sample sizes are required.
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PMID:Genetics of antipsychotic-induced side effects and agranulocytosis. 2133 63

The paper aims to review current evidence that supports the application of genetic information in the management and use of psychotropic medication. Although the importance of an individual's genetic makeup in the metabolism of drugs has been known for at least 50 years, it is only recently that such information is finding clinical application. A literature review of recent studies suggest that there are clear variations in the way people respond to psychotropic medication. These variations can be seen across racial and ethnic lines, and are genetically determined. The hope is that, in future we will be able to use genetic information to predict which patient will benefit from which drug and at what dose. In other fields of health care such as anticoagulant therapy, the application of pharmacogenetics is now established in routine clinical care. Several psychiatric pharmacogenetic tests are currently available, including tests for the determination of metabolic status, risk of agranulocytosis and metabolic syndrome, and selection of beneficial medications. Since nurses are the centrepiece of mental health care, these advances are likely to alter significantly future mental health nurse education and practice.
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PMID:Pharmacogenetics: a reality or misplaced optimism? 2251 71

Research into the use of clozapine in older people is somewhat scarce. Clozapine is associated with serious adverse effects such as agranulocytosis, seizures, myocarditis and metabolic syndrome. Other common undesirable effects such as sedation, constipation (which can be fatal), urinary incontinence and hypersalivation further limit its use. These adverse effects are particularly important for the use of clozapine in older people, who are generally more susceptible to medication-related adverse effects. Whilst clozapine should be used with caution in elderly people, strict monitoring procedures can help to prevent harmful effects through early detection, and certain management techniques exist to minimise them. This review outlines the epidemiology of clozapine-related adverse effects in older people and discusses potential prevention and management strategies.
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PMID:Adverse effects of clozapine in older patients: epidemiology, prevention and management. 2433 20

Antipsychotics remain the standard of care for individuals with schizophrenia, despite their association with adverse effects including extrapyramidal symptoms, metabolic syndrome and agranulocytosis. While the biological mechanisms underlying these side effects remain unresolved, it has been proposed that oxidative stress may play a role in their development. The aim of this study was to evaluate markers of oxidative stress associated with first- and second-generation antipsychotics, focusing on protein and lipid oxidation and expression of the antioxidant proteins peroxiredoxin-2 and peroxiredoxin-6. Following 28-day administration of haloperidol, clozapine or saline to adult rats, brain grey matter, white matter, serum and liver samples were obtained and lipid peroxidation, protein oxidation, peroxiredoxin-2 and peroxiredoxin-6 levels quantified. In grey matter, peroxiredoxin-6 was significantly increased in the haloperidol-exposed animals, with a trend towards increased lipid peroxidation also observed in this group. In liver, lipid peroxidation was increased in the clozapine-exposed animals, with a similar trend noted in the haloperidol group. Antipsychotics did not produce significant changes in serum or white matter. Our results suggest that haloperidol and clozapine may induce oxidative stress in brain and liver, respectively, consistent with the documented adverse effects of these agents.
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PMID:Effects of haloperidol and clozapine administration on oxidative stress in rat brain, liver and serum. 2568 43

Clozapine is a highly effective antipsychotic medication, which provides a range of significant benefits for patients with schizophrenia, and is the standard of care for treatment-resistant schizophrenia as well as for reducing the risk of suicidal behaviors in schizophrenia and schizoaffective disorder. However, clozapine is widely underutilized, largely because prescribing clinicians lack experience in prescribing it and managing its adverse events (AEs). Clozapine is associated with 3 uncommon but immediately dangerous AEs, agranulocytosis, myocarditis/cardiomyopathy, and seizures, as well as AEs that may become dangerous if neglected, including weight gain, metabolic syndrome and constipation, and others that are annoying or distressing such as sedation, nighttime enuresis and hypersalivation. Because of the risk of agranulocytosis, clozapine formulations are available only through restricted distribution via a patient registry, with mandatory, systematized monitoring for absolute neutrophil count using a specific algorithm. We identified articles on managing clozapine-associated AEs by searching PubMed using appropriate keywords and search techniques for each topic. A review of the prevalence and clinical characteristics of clozapine-associated AEs shows that these risks can be managed efficiently and effectively. The absolute risks for both agranulocytosis and myocarditis/cardiomyopathy are low, diminish after the first 6 months, and are further reduced with appropriate monitoring. Weight gain/metabolic disorders and constipation, which develop more gradually, can be mitigated with regular monitoring and timely interventions. Sedation, hypersalivation, and enuresis are common but manageable with ameliorative measures and/or medications.
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PMID:A Guide to the Management of Clozapine-Related Tolerability and Safety Concerns. 2745 14

Clozapine is a highly effective antipsychotic medication, which provides a range of significant benefits for patients with schizophrenia, and is the standard of care for treatment-resistant schizophrenia as well as for reducing the risk of suicidal behaviors in schizophrenia and schizoaffective disorder. However, clozapine is widely underutilized, largely because prescribing clinicians lack experience in prescribing it and managing its adverse events (AEs). Clozapine is associated with three uncommon but immediately dangerous AEs-agranulocytosis, myocarditis/cardiomyopathy, and seizures-as well as AEs that may become dangerous if neglected, including weight gain, metabolic syndrome and constipation, and others that are annoying or distressing such as sedation, nighttime enuresis and hypersalivation. Because of the risk of agranulocytosis, clozapine formulations are available only through restricted distribution via a patient registry, with mandatory, systematized monitoring for absolute neutrophil count using a specific algorithm. We identified articles on managing clozapine-associated AEs by searching PubMed using appropriate key words and search techniques for each topic. A review of the prevalence and clinical characteristics of clozapine-associated AEs shows that these risks can be managed efficiently and effectively. The absolute risks for both agranulocytosis and myocarditis/cardiomyopathy are low, diminish after the first six months, and are further reduced with appropriate monitoring. Weight gain/metabolic disorders and constipation, which develop more gradually, can be mitigated with regular monitoring and timely interventions. Sedation, hypersalivation, and enuresis are common but manageable with ameliorative measures and/or medications.
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PMID:Guide to the Management of Clozapine-Related Tolerability and Safety Concerns. 2773 2