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)

Suppositories are the preferable dosage form for patients at home or experiencing nausea. Serotonin (5-HT(3))-receptor antagonists are used to treat vomiting in intravenous or oral administration but not suppository form. Ramosetron hydrochloride (RAM) is a new 5-HT(3) antagonist which effectively inhibits vomiting, and we prepared RAM suppositories using Witepsol((R)) H-15 (H-15) containing Carbopol((R)) 934P (CP). The viscosity of suppository base and RAM release properties from suppositories were examined. Plasma RAM concentrations after administration of suppositories to rabbits were estimated and irritation of rectal tissues were observed. Antiemetic effects of suppositories were studied using ferrets. The base viscosity increased with addition of CP. Suppositories containing CP exhibited better absorption in rabbits compared to H-15 suppositories, correlated with release behavior. Suppositories containing 2% CP had 2.5 times larger AUC(0-24 h) than H-15 suppositories, and the MRT was prolonged by 5.8 h compared with i.v. administration. 10% CP suppositories administered to rabbits for 5 days did not irritate the tissues. Antiemetic studies indicated that 2% CP suppository of RAM might have the same effect as i.v. administration. These results suggest that RAM suppositories containing CP are safe and useful in once-a-day dosage form for treatment of chemotherapy-induced nausea.
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PMID:Mucoadhesive suppositories of ramosetron hydrochloride utilizing Carbopol. 1060 83

Withdrawal syndrome after discontinuing serotonin re-uptake inhibitors, especially paroxetine, is largely unknown to most physicians. Variable incidence has been reported. Our aim was to stress the main clinical features of this syndrome. Serotonin re-uptake inhibitor withdrawal syndrome generally begins within 24 to 48 hours after discontinuing the drug. Signs reach their maximum on day 5 and usually resolve within 2 to 3 weeks. Withdrawal syndrome is more common with short half-life drugs (paroxetine, fluvoxamine). The intensity of the clinical signs depends on the daily dose and how long the drug has been given. The main signs are dizziness, vertigo, headache, nausea, and flu-like symptoms as well as anxiety, confusion, irritability, excessive dreaming and insomnia. Risk factors usually stressed are poor treatment compliance, previous withdrawal syndrome with another drug, concomitant medication and alcohol consumption. The syndrome can be prevented by tapering off the dose and patient education. When a withdrawal syndrome is present, it is advisable to reintroduce the drug then withdraw gradually.
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PMID:[Paroxetine withdrawal syndrome]. 1085 79

Despite a rising worldwide epidemic of obesity there is currently only a very small number of anti-obesity drugs available to manage the problem. Large numbers of differing pharmacological agents reliably produce a reduction in food intake when administered acutely to animals, and when administered chronically they result in a significant decrease in body mass. Behavioural analysis of drug-induced anorexia in animals demonstrates that various compounds profoundly effect feeding behaviour in differing ways. This indicates the variety of mechanisms by which pharmacological agents can induce changes in food intake, body weight and eventually body composition. Some of the same drugs produce decreases in food intake and weight loss in humans. Some of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). Such drugs can be considered as "appetite suppressants" with clinical potential as anti-obesity agents. Other drugs induce changes in food intake and body weight through various physiological mechanisms inducing feelings of nausea or even by side effect related malaise. Of the drugs considered suitable candidates for appetite suppressants are agents which act via peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), or alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin and Melanocortins) or levels of the key CNS appetite monoamine neurotransmitters such as serotonin (5-HT) and noradrenaline (NA). Recently, the hormone leptin has been regarded as a hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The peptide itself stimulates leptin receptors and it links with POMC and MC-4 receptors. These receptors may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i) psychological experience and behavioural expression of appetite, (ii) metabolism and peripheral physiology, and (iii) functioning of CNS neural pathways. In humans, modulation of appetite may involve changes in total caloric consumption, subjective changes in feelings of hunger and fullness, preferences for specific food items, and general macronutrient preferences. These may be expressed behaviourally as changes in meal patterns, snacking behaviour and food choice. Within the next 20 years it is certain that clinicians will have a new range of anti-obesity compounds available to choose from. Such novel compounds may act on a single component of the appetite system or target a combination of these components detailed in this review. Such compounds used in combination with lifestyle changes and dietary intervention may be useful in dealing with the rising world epidemic of obesity.
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PMID:Pharmacology of appetite suppression. 1085 85

Data from 1413 outpatients in community-based clinical practices were collected in order to characterize the use and effectiveness of 5-HT(3) receptor antagonists for control of chemotherapy-induced nausea and vomiting (NV). Patients were divided by treatment starting date into six cohorts for trend analysis. In addition, NV symptoms were compared in 252 patients treated prior to the commercial introduction of the 5-HT(3) receptor antagonist antiemetics, and an equal number of patients treated after their introduction. A comparison of cohorts revealed a significant (P = 0. 027) downward trend over time for the frequency of post-treatment vomiting episodes, but not for frequency of post-treatment nausea (P = 0.69). The average duration of nausea following treatment increased significantly over time (P = 0.003). Although the introduction of 5-HT(3) receptor antagonist antiemetics has apparently led to a significant reduction in the frequency of post-treatment vomiting, there has been an accompanying increase in the duration of post-treatment nausea.
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PMID:Nausea and vomiting remain a significant clinical problem: trends over time in controlling chemotherapy-induced nausea and vomiting in 1413 patients treated in community clinical practices. 1098 49

Lilly is developing duloxetine, a 5-HT and norepinephrine uptake inhibitor as a potential treatment for depression and urinary incontinence. In Japan, it is being jointly developed with Shionogi [187401]. Phase III trials for depression and phase II trials for urinary incontinence are underway in Japan [296442,328887]. Lilly expects to file for depression in 2002 and phase III trials for urinary incontinence are planned to start enrollment by the end of 2000 [358429,370526,373870]. Duloxetine has a half-life of 10 to 15 h in humans, and parameters reach a steady-state after 3 days of daily administration. In a 6-week, open-label study duloxetine was safe and well tolerated in 79 clinically depressed patients. Clinical response occurred in 78% of patients, and remission occurred in 60%. Insomnia and nausea occurred with an incidence of 20% [300881]. Duloxetine may offer advantages over existing antidepressants, such as Lilly's fluoxetine, because of faster recovery and fewer side effects [190226]. In June 2000, Morgan Stanley Dean Witter predicted duloxetine would reach the market in 2002 with annual sales in this year of US $50 million, rising to $200 million in 2005 [373870]. In February 1999, Deutsche Bank predicted Lilly's sales at US $200 million in 2002 rising to $400 million in 2003 [316821]. In May 2000, Deutsche Bank had made further predictions, stating that filing for duloxetine is expected in the fourth quarter of 2001, and peak sales are expected to exceed US $500 million. Also in February 1999, Lehman Brothers predicted the first major launch date (US and ex-US) to be 2002, with the year of peak sales to be 2008 [319225]. In August 1999, this prediction changed, and the expected launch date became 2001, with an 80% probability of reaching the market and sales peaking at US $150 million in 2012 [349228].
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PMID:Duloxetine Eli Lilly & Co. 1124 87

The serotonin syndrome results when serotonergic activity increases to abnormally high levels. It occurs with selective serotonin reuptake inhibitors (SSRIs), opioids, and other serotonergic agents when the serotonin system has been modulated by another serotonergic agent or compromised by illness. Although the symptoms are quite variable, the syndrome is characterized by a triad of altered mental status, neuromuscular abnormalities, and autonomic dysfunction. The authors report the probable occurrence of the serotonin syndrome with serotonin receptor subtype 3 (5-HT(3)) antagonist therapy when used to control nausea associated with chemotherapy in two seriously ill children. The first case involves combined use with mirtazapine and the second with fentanyl. These agents may pose a potential risk when used in such combination in seriously ill patients.
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PMID:Possible serotonin syndrome in association with 5-HT(3) antagonist agents. 1135 Nov 16

Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).
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PMID:Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine. 1138 69

Ingestion of toxin, traumatic events, adverse drug reactions, and motion can all result in nausea and emesis. In addition, cyclic vomiting syndrome is quite prevalent in the pediatric population. Coordination of the various autonomic changes associated with emesis occurs at the level of the medulla oblongata of the hindbrain. Chemosensitive receptors detect emetic agents in the blood and relay this information by means of neurons in the area postrema to the adjacent nucleus tractus solitarius (NTS). Abdominal vagal afferents that detect intestinal luminal contents and gastric tone also terminate in the NTS (gelatinosus, commissural, and medial subnuclei). The NTS is viscerotopically organized into subnuclei that subserve diverse functions related to swallowing (subnucleus centralis), gastric sensation (subnucleus gelatinosus), laryngeal and pharyngeal sensation (intermediate and interstitial NTS), baroreceptor function (medial NTS), and respiration (ventrolateral NTS). Neurons from the NTS project to a central pattern generator (CPG), which coordinates the sequence of behaviors during emesis, as well as directly to diverse populations of neurons in the ventral medulla and hypothalamus. Thus, it is critical to realize that there is not an isolated "vomiting center," but rather groups of loosely organized neurons throughout the medulla that may be activated in sequence by a CPG. The newer antiemetic agents appear to block receptors in the peripheral endings of vagal afferents to reduce "perception" of emetic stimuli and/or act in the dorsal vagal complex. A primary site of action of 5-HT(3)-receptor antagonists is by means of the vagal afferents. Neurokinin-1 receptor (NK(1)R) antagonists are antiemetics, because they act at a site in the dorsal vagal complex. Part of their effectiveness may be the result of inhibition of the NK(1)R on vagal motor neurons to prevent fundic relaxation, which is a prodromal event essential for emesis. Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive component of marijuana, can be therapeutically useful as an antiemetic. The site of action of Delta(9)-THC is on cannabinoid CB1 receptors in the dorsal vagal complex. However, it decreases fundic tone and antral motility. It is not easy to predict the potential antiemetic effects of drugs that alter motility. Although antiemetic drugs are available for management of acute chemotherapeutic-induced emesis, few treatments are effective for delayed emesis or cyclic vomiting syndrome.
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PMID:Central neurocircuitry associated with emesis. 1174 34

Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans show only minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than three attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum toxin is under investigation.
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PMID:Advances in pharmacological treatment of migraine. 1177 89

Syncope is defined as a temporary interruption of cerebral perfusion with a sudden and transient loss of consciousness and spontaneous recovery. Approximately one third of the population experiences syncope at least once during a lifetime. Presyncopal signs and symptoms, including weakness, headache, blurred vision, diaphoresis, nausea, and vomiting are sometimes present for seconds or minutes prior to loss of consciousness. After syncope, the patients may present with persisting drowsiness, headache, dizziness, nausea, but not usually confusion. Causes of syncope have been categorized as cardiovascular, non-cardiovascular, and unexplained. Cardiovascular causes can be subdivided into structural heart disease, coronary heart disease, and arrhythmia. Non-cardiovascular causes include neurological, metabolic, psychiatric and other disorders.Orthostatic hypotension - one of the most frequent causes of syncope - has manifold etiologies comprising various neurological and internal diseases. Orthostatic hypotension usually can be attributed to an impairment of peripheral vasoconstriction or to a reduction of the intravascular volume. Signs and symptoms, including the above prodromi are often present just after rising from a supine or sitting position. Frequently, blood pressure decreases significantly without an increase in heart rate. Autonomic cardiovascular modulation is often reduced. Many of the patients with "unexplained" syncope experience neurally mediated (i. e. neurocardiogenic or vasovagal) syncope. In these patients, cardiovascular control may be stable for an extended period of time during orthostatic stress, then there is a sudden decrease in blood pressure and heart rate. Neurocardiogenic or neurally mediated syncope can be associated with painful or emotionally stressful situations such as anxiety or fear, with prolonged standing or specific trigger situations such as micturition, defecation, coughing or sneezing, visceral or carotid sinus stimulation, or with trigeminal or glossopharyngeal neuralgia. So far, the mechanisms of neurocardiogenic syncope are not completely understood. The passive 60 degrees to 70 degrees head-up tilt test is useful for the diagnosis of orthostatic and neurally mediated syncope. The sensitivity of the test can be improved by additional pharmacological provocation, e. g. by isoproterenol, or by increased orthostatic stress using lower body negative pressure stimulation. For the treatment of syncope one should first consider non-pharmacological options. Patients with orthostatic hypotension should avoid rapid changes of the body position from supine to standing, as well as high room temperature or other situations inducing peripheral vasodilatation. An increased intake of sodium and fluids, mild physical exercise or so-called postural counter-maneuvers can improve orthostatic tolerance. Among the drugs recommended for pharmacologic treatment are mineralocorticoids (e. g. fludrocortisone), vasoconstrictor agents (e. g. ephedrine, midodrine), adenosine receptor blockers (theophylline) and beta2-blockers (propanolol), anticholinergic agents, e. g. scopolamine or disopyramide, and negative cardiac inotropes, e. g. beta1-adrenergic blockers or disopyramide. Serotonin reuptake inhibitors (e. g. fluoxetine, sertraline), alpha2-adrenergic agonists (clonidine), central nervous system stimulants such as methylphenidate or phentermine are thought to be beneficial in specific cases. Cardiac pacemakers often seem to be recommended without adequate indication. The antidiuretic, V2-receptor specific, vasopressin analogue desmopressin increases the intravascular volume. Erythropoietin improves anemia and red blood cell decrease and augments blood pressure and cerebral oxygenation. In postprandial hypotension, octreotide, a somatostatin analogue, prostaglandin inhibitors such as indomethacin or ibuprofen, as well as metoclopramide or two cups of coffee per day might be beneficial.
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PMID:[Syncope - a systematic overview of classification, pathogenesis, diagnosis and management]. 1182 26


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