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)

Stress urinary incontinence (SUI) is the accidental leakage of urine associated with physical activities such as running, jumping or lifting or with sneezing and coughing. For many patients it can be a very bothersome symptom, causing social isolation, loss of self-esteem and increased financial outlays. Although there is currently no medication approved worldwide for the treatment of SUI, a variety of off-label agents are sometimes prescribed. Duloxetine (LY-248686; Eli Lilly), a new centrally acting compound with dual activity as a serotonin and noradrenaline re-uptake inhibitor, offers a promising new approach for treatment. Due to its inhibition of presynaptic neuron re-uptake of serotonin and noradrenaline in the sacral spinal cord, duloxetine is believed to increase the strength of urethral sphincter contractions and thereby prevent accidental urine leakage by increasing urethral closure pressure. In three published trials in women with the predominant symptom of SUI, duloxetine significantly reduced the number of incontinence episodes compared to placebo. Adverse events were usually observed early in treatment, were mild-to-moderate in severity and were transient. Nausea was the most common reason for discontinuation.
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PMID:Duloxetine: a serotonin-noradrenaline re-uptake inhibitor for the treatment of stress urinary incontinence. 1294 99

Obesity is a multifactorial, chronic disorder that has reached epidemic proportions in most industrialised countries and is threatening to become a global epidemic. Clinical management of obese patients is complex and serious doubts have arisen with regard to safety and efficacy of drug therapy. Following the withdrawal of fenfluramine and dexfenfluramine in 1997, interest has focused on novel anti-obesity drugs. Pharmacological approaches to the management of obesity can, in broad terms, use different distinct strategies: firstly, to reduce energy intake; secondly, to increase energy expenditure; and thirdly, to alter the partitioning of nutrients between fat and lean tissue. Sibutramine is a serotonin-noradrenaline (norepinephrine) reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The pharmacological mechanisms by which sibutramine exerts its weight loss effect are likely due to a combination of reduced appetite, feelings of satiety and possibly the induction of thermogenesis. The efficacy of sibutramine for inducing initial weight loss and the subsequent maintenance of weight loss is well proven in short- and long-term clinical trials of up to 2 years' duration. Most individual placebo-controlled trials and pooled estimates found that the drug produced statistically significant greater weight loss than placebo at all observed endpoints (weighted mean difference for weight change at 8 weeks: -3.4 kg; mean difference range for weight change at 6 months: -4.0 to -9.1 kg; and at 1 year: -4.1 to -4.8 kg). The most frequent dosage regimen in these trials was 10-20 mg daily. Findings suggested a dose-effect relationship in terms of weight loss. Sibutramine was also associated with better weight maintenance relative to placebo (statistically significant difference). Results from mainly small trials showed that sibutramine produced more favourable outcomes in terms of loss of fat mass, reduction in body mass index and loss of > or = 5-10% of initial bodyweight. The most commonly reported adverse effects of sibutramine are headache, constipation and nausea. Certain adverse events associated with the nervous system, including dizziness, dry mouth and insomnia, are reported by > 5% of patients receiving sibutramine. Increases in blood pressure and heart rate were possible adverse effects that require regular monitoring especially in obese hypertensive patients. Neither left-sided cardiac valve disease nor primary pulmonary hypertension was associated with the use of sibutramine. The assessment of the benefit-risk profile of sibutramine remained positive, although the product must be kept under regular review.
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PMID:A benefit-risk assessment of sibutramine in the management of obesity. 1458 64

Hypericum perforatum is an herbaceous perennial plant, also known as "St. John's wort", used popularly as a natural antidepressant. Although some clinical and experimental studies suggest it has some properties similar to conventional antidepressants, the proposed mechanism of action seems to be multiple: a non-selective blockade of the reuptake of serotonin, noradrenaline and dopamine; an increase in density of serotonergic and dopaminergic receptors and an increased affinity for GABAergic receptors; moreover, the inhibition of monoaminoxidase enzyme activity has been involved. In any case, the increase of monoamine concentrations in the synaptic cleft resembles several actions exerted by clinically effective antidepressants. In the present article, we review some of the controversial evidence derived from clinical and experimental studies suggesting that H. perforatum exerts antidepressant-like actions, and we also review some of its side effects, such as nausea, rash, fatigue, restlessness, photosensitivity, acute neuropathy, and even episodes of mania and serotonergic syndrome when administered simultaneously with other antidepressant drugs. All of the foregoing suggests that H. perforatum extracts appear to exert potentially significant pharmacological activity involving several neurotransmission systems supposed to be involved in the pathophysiology of depression. However, little information regarding the safety of H. perforatum is available, including potential herb-drug interactions. There is a need for additional research on the pharmacological and biochemical activity of H. perforatum, as well as its side-effects and its several bioactive constituents to further elucidate the mechanisms of antidepressant actions.
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PMID:A review of clinical and experimental observations about antidepressant actions and side effects produced by Hypericum perforatum extracts. 1469 32

Venlafaxine is the first of a group of antidepressants that show dual reuptake inhibition of serotonin and noradrenaline (SNRIs). Originally marketed in an immediate release (IR) formulation a microencapsulated, extended release (XR) formulation is now available. Significant differences exist between these two formulations with respect to pharmacokinetic parameters which have an impact on clinical use. The XR has lower maximum plasma concentrations (Cmax) and achieves these at a later time (higher Tmax). The longer apparent elimination half-life of the drug after single XR doses suggests that it is suitable for once daily dosing compared with the twice daily dosing regimen required by the IR formulation. With respect to antidepressant efficacy the XR formulation is equivalent to other marketed antidepressants and to the IR formulation. Consistent with its pharmacokinetic properties the use of the XR formulation is associated with less nausea and dizziness at the initiation of therapy. While in clinical usage XR might be expected to increase compliance with medication and to reduce discontinuation syndromes there are few comparative studies for which this has been evaluated. The XR formulation of venlafaxine is no worse than the IR form with respect to tolerability and offers some benefits to patients in terms of ease of use. On the other hand there does not appear to be any increase in the efficacy of the active agent.
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PMID:The treatment of depression with different formulations of venlafaxine: a comparative analysis. 1471 6

Milnacipran is a new antidepressant which inhibits equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo with no effect on dopamine reuptake. Microdialysis studies have shown increased extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor. In particular, and unlike tricyclic antidepressants (TCAs), it has no activity at noradrenergic, muscarinic or histaminergic receptors. Contrary to TCAs, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. Milnacipran has a high bioavailability, low plasma protein binding, and is largely eliminated in the urine as the parent drug or as a glucuronide. These features suggest that interactions with other drugs given concurrently are unlikely. Studies in patients with liver dysfunction and in the elderly suggest that dose adjustment is not necessary. In patients with renal impairment, decreased elimination of milnacipran is correlated to the degree of renal impairment allowing an easy dosage adjustment. An intermediate half-life of approximately 8 h is compatible with twice-daily administration. Clinical studies comparing milnacipran, placebo and other antidepressants provide evidence of its efficacy in moderate to severe depression in both hospitalized and outpatient settings. Meta-analyses of the original data of controlled trials comparing milnacipran with imipramine or selective serotonin reuptake inhibitors (SSRIs) show that milnacipran provides antidepressant efficacy similar to that of TCAs and significantly superior to that of SSRIs. An analysis of a database of over 3300 patients shows that both the general and cardiovascular tolerability of milnacipran are superior to those of TCAs with notably less cholinergic side effects. The tolerance of milnacipran was comparable to that of SSRIs with a higher incidence of dysuria with milnacipran but a higher frequency of nausea and anxiety with the SSRIs. Milnacipran represents an interesting new therapeutic option in depression, being as well tolerated as the SSRIs but offering clinical efficacy similar to the TCAs.
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PMID:Milnacipran, a new specific serotonin and noradrenaline reuptake inhibitor. 1498 77

Tramadol is a centrally acting analgesic with weak opioid agonist properties, which also has monoaminergic activity, exerted via inhibition of neuronal uptake of serotonin and norepinephrine. Tramadol is generally well tolerated and the most common adverse events are nausea, dizziness, drowsiness, sweating, vomiting and dry mouth. Currently it was examined by which principal mechanism tramadol induces oral dryness. The effects of intravenous administration (+/-)-tramadol were studied in rats on the flow of saliva in response to a peripheral cholinergic stimulus or to reflex activation involving the relay of impulses in the central nervous system. In pentobarbitone-anaesthetized rats, the salivary secretion to acetylcholine (0.1-10 micromol/kg IV) was increased by up to 110% by tramadol (1-5 mg/kg IV) and the protein concentration therein by up to 400%. The administration alpha- and beta-adrenoceptor antagonists resulted in almost identical acetylcholine-evoked responses as in the absence of tramadol. The secretory response to the application of citric acid on the tongue of the rat was reduced by 38% and by 64%, respectively, at 5 and 10 mg/kg IV of tramadol (p < 0.05-0.01). Thus, tramadol exerts its principal xerogenic effect by activating inhibitory pathways in the central nervous system and has no anticholinergic effect on the salivary glands at dosages that may be clinically relevant. Furthermore, the tramadol-induced increase of the acetylcholine-evoked secretion occurred at a glandular level and depended most likely on a release of noradrenaline from glandular nerve terminals.
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PMID:The xerogenic potency and mechanism of action of tramadol inhibition of salivary secretion in rats. 1548 38

Duloxetine is an orally administered, balanced, dual serotonin and norepinephrine (noradrenaline) reuptake inhibitor that increases neural input to the urethral sphincter, thereby relieving the symptoms of stress urinary incontinence (SUI). Duloxetine 40 mg twice daily for 12 weeks reduced the median incontinence episode frequency (IEF) to a significantly greater extent than placebo in women with predominant symptoms of SUI. In most studies, Incontinence Quality of Life (I-QOL) questionnaire total scores were significantly improved compared with placebo. In a dose-escalation study in women with severe SUI scheduled for continence surgery, duloxetine 80-120 mg/day for 8 weeks significantly reduced IEF and increased I-QOL total scores compared with placebo, and caused 20% of recipients to reconsider their willingness to undergo surgery. Duloxetine or duloxetine plus pelvic floor muscle training (PFMT) were more effective in reducing the median IEF than PFMT alone or no treatment in women with SUI. Mean I-QOL total scores suggested that combination therapy was more effective than either therapy alone. Nausea was the most frequent adverse event and was the main cause for discontinuing duloxetine therapy.
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PMID:Duloxetine: in stress urinary incontinence. 1551 54

Milnacipran is a novel serotonin noradrenaline reuptake inhibitor. The authors describe the use of milnacipran for the treatment of chronic pain in a series of patients. There were 5 outpatients who suffered chronic pain for at least 3 months. None of these patients met the DSM-IV criteria for a major depressive disorder. Chronic pain was assessed clinically by means of a visual analog scale (VAS) before and 12 weeks after the start of the milnacipran treatment or at the time the drug was stopped. The duration of pain was 17.8 +/- 9.3 months (mean +/- SD), and the baseline VAS score was 88.2 +/- 6.3 points. Milnacipran was administered at 50 to 150 mg/day, and the dose at 12 weeks or at the time the drug was stopped was 85.0 +/- 31.3 mg/day. The mean +/- SD decrease in VAS at this time was 61.2 +/- 15.5%. Three patients showed marked improvement (decrease in VAS, >75%). Their decreases in VAS scores were 86.5%, 85.7%, and 77.6%. One patient showed mild improvement (42.0% decrease in VAS). These 4 patients tolerated the drug well. The fifth patient experienced nausea and discontinued treatment after 4 weeks. The VAS decrease for this patient was 14.3%. Results of this study show milnacipran to be beneficial in patients with chronic pain. This drug should be studied further for its effectiveness in the treatment of chronic pain.
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PMID:Effectiveness of milnacipran for the treatment of chronic pain: a case series. 1560 99

In this study, we aimed at evaluating the efficacy and safety of venlafaxine extended release 75 mg, a serotonin and noradrenaline reuptake inhibitor, in the treatment of patients with premature ejaculation. Thirty-one patients with intravaginal ejaculation latency of less than 2 min received venlafaxine XR (75 mg/day) or placebo during a 2-week period for each agent with a washout period of 1 week between agents. Efficacy was assessed for each agent with changes in ejaculation latency measured with a stopwatch and sexual satisfaction scores of patients and partners. Side-effects, pre- and post-treatment levels of biochemical and spermiogram parameters, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and total testosterone were recorded for each agent. Statistical analysis was performed on 21 patients. After 2 weeks of treatment with placebo and venlafaxine, ejaculation latency time was significantly increased from 60.1 +/- 39.1 to 126.9 +/- 98.3 sec and to 178.1 +/- 122.8 sec, respectively (p < 0.0001 for each one). However, the difference between the two agents was insignificant (p = 0.144). Venlafaxine and placebo increased sexual satisfaction scores of both patients and partners similarly, no statistically significant difference was found between them in this respect. The incidence of side-effects with venlafaxine was indifferent than that of placebo (p > 0.1) except nausea (p = 0.035). Both agents did not change the blood and spermiogram parameters significantly, except FSH increases. Short-term use of venlafaxine XR 75 mg has only a placebo effect on ejaculation latency and sexual satisfaction scores, therefore, is not appropriate for the patients with premature ejaculation. Further dose-time studies are required to draw final conclusions on the inefficacy of this drug in premature ejaculation.
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PMID:Venlafaxine extended release for the treatment of patients with premature ejaculation: a pilot, single-blind, placebo-controlled, fixed-dose crossover study on short-term administration of an antidepressant drug. 1567 21

Venlafaxine is a new antidepressant that inhibits the reuptake of both 5-hydroxytryptamine (serotonin; 5-HT) and noradrenaline (NA). It is somewhat more potent as an inhibitor of the reuptake of 5-HT than NA. Its potency to inhibit the reuptake of 5-HT is comparable to that of tricyclic antidepressants (TCAs) such as amitriptyline or imipramine, but it is less potent than these drugs at inhibiting the reuptake of NA. Consequently, at low doses, venlafaxine may be a more effective inhibitor of the reuptake of 5-HT than that of NA. The major metabolite of venlafaxine in humans, O-desmethylvenlafaxine, has comparable potency to the parent drug for inhibiting the reuptake of either NA or 5-HT in vitro, but it is less potent in vivo. Both venlafaxine and O-desmethylvenlafaxine are essentially devoid of activity at muscarinic cholinergic, H1 histaminergic, and 1-adrenoceptors. This probably accounts for venlafaxine having a side-effect profile similar to that of selective serotonin reuptake inhibitors (SSRIs) rather than that of TCAs. Venlafaxine is subject to extensive first-pass metabolism and is metabolised by the cytochrome P450 isoenzyme IID6 in the liver. The half-life of venlafaxine is 3-4 h and that of its principal metabolite is about 10 h. The daily dose of venlafaxine can be administered as either two or three divided doses without altering significantly the pharmacokinetics of venlafaxine. The most common side-effects of venlafaxine are nausea, sedation, dizziness, dry mouth and sweating, as well as sexual dysfunctions, primarily problems with erection and delayed ejaculation. In some patients, venlafaxine also causes sustained elevations in both systolic and diastolic blood pressure; this effect is dose-dependent. Venlafaxine is much safer in overdosage than the TCAs. Antidepressant efficacy of venlafaxine has been found both in out-patients and in-patients. In general, its efficacy is comparable to that of comparator drugs (primarily TCAs or SSRIs), and in some cases even greater, and its efficacy is greater than that measured with placebo.
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PMID:Venlafaxine:a novel antidepressant compound. 1598 62


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