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)

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of aripiprazole are discussed. Aripiprazole is a third-generation antipsychotic agent indicated for use in the treatment of schizophrenia. Unlike other antipsychotics, aripiprazole demonstrates mixed D2 and serotonin (5-HT1A) receptor agonist-antagonist activity that is hypothesized to improve schlzophrenia's positive and negative symptoms; the drug has been referred to as a dopamine-serotonin stabilizer. Aripiprazole is well absorbed, with peak plasma concentrations occurring within three to five hours after administration. The oral availability is 87%. The mean elimination half-life is about 75 hours for aripiprazole and 94 hours for its active metabolite. In controlled, randomized, multicenter trials, aripiprazole has demonstrated efficacy in the treatment of schizophrenia comparable to that of haloperidol and superior to placebo. In a single clinical trial, aripiprazole was superior to placebo in the treatment of acute mania. The most frequent adverse effects are headache, anxiety, insomnia, nausea, vomiting, and lightheadedness. Because aripiprazole is a substrate of both cytochrome P-450 isoenzymes 3A4 and 2D6, there is a potential for other drugs to affect its metabolism. The recommended starting dosage is 10 or 15 mg daily, preferably administered with meals. Aripiprazole offers an alternative to second-generation antipsychotic agents in the treatment of schizophrenia.
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PMID:Aripiprazole. 1468 20

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

Pharmacogenomics is research to study the drug treatment responses in subgroups of patients according to their genetic variants or genetic expression information. Methadone maintenance treatment, which is usually prescribed for patients with heroin dependence, was launched in Taiwan by the government in 2006. In this study, 366 patients who had taken methadone continually in the previous 7 days were examined. Data from administration of the Treatment Outcomes Profile (TOP), Severity of Dependence Scale (SDS), Clinical Opioid Withdrawal Scale (COWS), and Treatment Emergent Symptoms Scale (TESS) were obtained from patients' report records. Genes encoding the liver cytochrome P-450 (CYP) enzymes that are involved with the metabolism of methadone (CYP2B6, 3A4 and 2C19) were selected and genotyped in this cohort. We found that the SNPs on CYP2B6 were associated with plasma S-methadone concentration; SNPs on CYP3A4 were associated with withdrawal symptoms and side effects; and SNPs on CYP2C19 were associated with methadone dose. SNPs in the genes encoding the morphine phase II metabolic enzyme, UGT2B7, were associated with withdrawal symptom scores. In pharmacodynamic genes, the SNPs on OPRM1 were associated with insomnia and change in libido side effects. We conclude that SNP markers may be useful for future methadone dosage adjustment and to reduce adverse reactions.
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PMID:Pharmacogenomics study in a Taiwan methadone maintenance cohort. 2527 38