Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproic acid is a branched-chained fatty acid, structurally unrelated to any other antiepileptic drug. Since publication of the original review in the Journal in 1977, several clinical trials have documented its efficacy and safety in adults and children for the treatment of generalised seizures (absence, tonic-clonic, myoclonic), partial seizures (simple, complex, secondarily generalised) and compound/combination seizures (including those refractory to treatment with other antiepileptic drugs). Valproic acid monotherapy has demonstrated efficacy equivalent to that of carbamazepine, phenytoin, and phenobarbital in the treatment of both generalised and partial seizures and ethosuximide in the treatment of absence seizures. Adverse effects associated with the drug are primarily gastrointestinal (nausea, vomiting, dyspepsia) in nature, although the use of enteric-coated formulations has reduced the incidence of abdominal discomfort. Weight gain, tremor and transient hair loss are commonly reported. Importantly, valproic acid has minimal neurological adverse effects (sedation, ataxia, impairment of cognitive function) compared with other antiepileptic drugs, a finding that may be of particular relevance in many patients with epilepsy. The incidence of rare, fatal liver failure has been greatly reduced by identifying and avoiding administration of valproic acid to high risk patient populations. An estimated risk of 1 to 2% for neural tube defects, predominantly spina bifida aperta, with maternal use of valproic acid therapy has been reported. Valproic acid inhibits hepatic drug metabolism and displaces other highly bound drugs from their plasma protein binding sites. Therefore, coadministered drugs which are highly protein bound or hepatically metabolised may require dosage adjustment. Enzyme-inducing antiepileptic drugs may increase valproic acid metabolism and necessitate increasing its dosage. Thus, comparative trials and extensive clinical experience have demonstrated the efficacy and tolerability of valproic acid and support its role as a valuable and well established first-line treatment for patients with a broad range of seizure types.
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PMID:Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. 751 5

Panic disorder, a psychiatric disorder characterised by frequent panic attacks, is the most common anxiety disorder, affecting 2 to 6% of the general population. No one line of treatment has been found to be superior, making a risk-benefit assessment of the treatments available useful for treating patients. Choice of treatment depends on a number of issues, including the adverse effect profile, efficacy and the presence of concomitant syndromes. Tricyclic antidepressants (TCAs) are beneficial in the treatment of panic disorder. They have a proven efficacy, are affordable and are conveniently administered. Adverse effects, including jitteriness syndrome, bodyweight gain, anticholinergic effects and orthostatic hypotension are commonly associated with TCAs, but can be managed successfully. Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors are also potential first line agents and are well tolerated and effective, with a favourable adverse effects profile. There is little risk in overdose or of anticholinergic effects. Adverse effects include sedation, dyspepsia and headache early in treatment, and sexual dysfunction and increased anxiety, but these can be effectively managed with proper dosage escalation and management. Benzodiazepines are an effective treatment, providing short-term relief of panic-related symptoms. Patients respond to treatment quickly, providing rapid relief of symptoms. Adverse effects include ataxia and drowsiness, and cognitive and psycho-motor impairment. There are reservations over their first-line use because of concerns regarding abuse and dependence. Monoamine oxidase inhibitors, because of their adverse effects profile, potential drug interactions, dietary restrictions, gradual onset of effect and overdose risk, are not considered to be first-line agents. They are effective however, and should be considered for patients with refractory disease. Valproic acid (valproate sodium), while not intensively studied, shows potential for use in panic disorder. More studies are needed in this area before the available data can be confirmed. As a supplement to drug therapy, cognitive behavioural therapy is effective. It is well tolerated, and may be beneficial in certain clinical situations. Its main drawback is the time commitment and effort needed to be made by the patient.
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PMID:A risk-benefit assessment of pharmacological treatments for panic disorder. 963 87

4-Hydroxyandrost-4-ene-3,17-dione (formestane) is a selective aromatase inhibitor. It is indicated for postmenopausal patients with advanced breast cancer. The aim of the present study was to investigate the effect of 4-hydroxyandrost-4-ene-3,17-dione on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acid. The experiments were carried out in the ovariectomized and sham-operated female Wistar rats. Formestane (20 mg/kg, i.m., daily) was administered to animals for 2 weeks. Twenty four hours after the last drug administration, rats were anesthetized with ethyl urethane. 4-(14)C-cholesterol (740 kBq/kg, s.a. 2.28 GBq/mmol) was infused for 1 min by catheter inserted into the jugular vein. Bile samples were assayed for total 14C radioactivity 14C-bile acids were determined in bile (after thin-layer chromatographic separation) by the use of isotopic technique with liquid scintillator. Previous studies showed that systemic adverse effects occurred in about 12% of patients following intramuscular drug administration. Many of them such as hot flushes, vaginal spotting and emotional lability were related to the mechanism of action of formestane i.e. estrogen suppression. Lethargy, rash, nausea, dizziness, indigestion, ataxia, cramps and facial swelling have also been reported. The results of the present study have shown that formestane administered to the female ovariectomized rats decreased the bile secretion and diminished conversion of 4-(14)C-cholesterol to trihydroxy bile acids. The decreased synthesis of trihydroxy bile acids and increased concentrations of cholesterol and litocholic acid in bile may be associated with increased risk of gallstone formation.
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PMID:Effect of 4-hydroxyandrost-4-ene-3,17-dione (formestane) on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acids. 1638 15

Thirty patients with different forms of epilepsy were treated with toreal in dosage 200 mg per day. The clinical efficacy was assessed after 8 and 12 weeks. Side-effects and changes of laboratory parameters were assessed taking into account their intensity, duration and possible relation to the drug. Toreal was most effective in symptomatic local forms of epilepsy (76-95%) and less effective in idiopathic forms (up to 70%). In the period of dose titration, higher fatigue (70%), sleepiness (53.33%) were recorded more often than dizziness, paresthesias, dry mouth, diplopia, dyspepsia, ataxia and others side-effects. Higher fatigue remained in 70% of patients to the end of 12th week while the frequency of other side- effects has decreased. Overall, the severity of side-effects was mild that did not lead to changing of dose or drug's withdrawal.
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PMID:[The use of toreal in the monotherapy of epilepsy in adults]. 1936 70