Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Derived from the aerial parts of the plant, St. John's wort generally is used for depression, seasonal affective disorder, and anxiety. Products currently are standardized based on hypericin content, although the hyperforin and bioflavonoid contents are also believed responsible for activity. St. John's wort is metabolized primarily by the liver. Some studies comparing St. John's wort to standard antidepressants suggest that it may be as effective as imipramine or selective serotonin reuptake inhibitors (SSRIs) to treat mild to moderate depression. Results from another clinical trial indicate that the effectiveness of St. John's wort is comparable to paroxetine, an SSRI, in the treatment of moderate to severe depression and is well tolerated. But a meta-analysis shows that data are inconsistent. Studies also show possible efficacy in the management of anxiety and premenstrual syndrome, although additional research is necessary. St. John's wort can interact with many medications owing to induction of cytochrome P-450 3A4 and other mechanisms. Significant interactions include decreased efficacy of antiretrovirals, cyclosporine, tacrolimus, antiepileptics, irinotecan, and other chemotherapeutic agents. Serotonin syndrome may occur when St. John's wort is combined with sympathomimetics, antidepressants, or triptans. Frequently reported adverse events include nausea, headache, constipation, dizziness, confusion, fatigue, and dry mouth. St. John's wort should be used under medical supervision.
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PMID:About the cover: St. John's wort. 1673 73

PURPOSE The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, and place in therapy of dalfampridine are reviewed. SUMMARY Dalfampridine is a novel drug with a unique mechanism for the symptomatic management of multiple sclerosis (MS) among all classifications. Dalfampridine was approved in January 2010 to improve walking for patients with MS. Dalfampridine blocks potassium channels on demyelinated neurons and allows normal electrical conduction, thus improving locomotor difficulty. Dalfampridine is rapidly absorbed after oral administration, reaching its peak plasma concentration in 1.3 hours. Approximately 95.9% of dalfampridine and its metabolites (3-hydroxy-4-aminopyridine and 3- hydroxy-4-aminopyridine sulfate) is excreted in the urine. Dalfampridine is not an inhibitor or inducer of a major cytochrome P-450 isoenzyme; therefore, the potential for drug-drug interactions is minimal. Clinical studies have shown dalfampridine to improve walking speed. The dosage of dalfampridine varied in clinical trials, but the recommended dosage is 10 mg orally twice daily. Dalfampridine is not appropriate for patients with seizures or moderate-to-severe renal impairment. Phase III studies found that extended-release fampridine 10 mg twice daily is well tolerated. The most frequent adverse events reported in dalfampridine clinical trials were insomnia, dizziness, headache, nausea, and weakness. The Food and Drug Administration has required the manufacturer to have a risk evaluation and mitigation strategy for dalfampridine. Ongoing trials will determine the long-term benefit of dalfampridine. CONCLUSION Dalfampridine is a potassium channel blocker that has demonstrated efficacy for improving the symptoms of MS. Several studies have demonstrated increased walking speed in patients, though high doses should be avoided due to the risk of seizures.
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PMID:Dalfampridine: a new agent for symptomatic management of multiple sclerosis. 2213 60

Peripheral T-cell lymphoma is a heterogenous non-Hodgkin Lymphoma with historically poor outcomes. Currently, response rates remain poor with traditional chemotherapy and many of those responding to initial therapy will relapse. Belinostat (Beleodaq, Spectrum Pharmaceuticals) is a histone deacetylase inhibitor (HDACi) approved for use in relapsed or refractory peripheral T-cell lymphoma (PTCL). Belinostat is metabolized hepatically through cytochrome P-450 enzymes 3A4, 2C9, and 2A6; however, no empiric dosage adjustments of belinostat are recommended during concurrent use of inhibitors or inducers of these enzymes. Belinostat's efficacy has been evaluated in a clinical trial showing an overall response rate (ORR) of 25.8% and a median duration of response of 8.4 months. Belinostat is generally well tolerated, with the most common adverse reactions (>25%) being nausea, vomiting, fatigue, pyrexia, and anemia in patients with relapsed or refractory PTCL. Belinostat is a safe and effective treatment option for relapsed and refractory peripheral T-cell lymphoma, with many future applications currently being investigated.
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PMID:Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. 2692 Oct 86


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