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)

The endogenous cannabinoid (CB) (endocannabinoid) signaling system is involved in a variety of (patho)physiological processes, primarily by virtue of natural, arachidonic acid-derived lipids (endocannabinoids) that activate G protein-coupled CB1 and CB2 receptors. A hyperactive endocannabinoid system appears to contribute to the etiology of several disease states that constitute significant global threats to human health. Consequently, mounting interest surrounds the design and profiling of receptor-targeted CB antagonists as pharmacotherapeutics that attenuate endocannabinoid transmission for salutary gain. Experimental and clinical evidence supports the therapeutic potential of CB1 receptor antagonists to treat overweight/obesity, obesity-related cardiometabolic disorders, and substance abuse. Laboratory data suggest that CB2 receptor antagonists might be effective immunomodulatory and, perhaps, anti-inflammatory drugs. One CB1 receptor antagonist/inverse agonist, rimonabant, has emerged as the first-in-class drug approved outside the United States for weight control. Select follow-on agents (taranabant, otenabant, surinabant, rosonabant, SLV-319, AVE1625, V24343) have also been studied in the clinic. However, rimonabant's market withdrawal in the European Union and suspension of rimonabant's, taranabant's, and otenabant's ongoing development programs have highlighted some adverse clinical side effects (especially nausea and psychiatric disturbances) of CB1 receptor antagonists/inverse agonists. Novel CB1 receptor ligands that are peripherally directed and/or exhibit neutral antagonism (the latter not affecting constitutive CB1 receptor signaling) may optimize the benefits of CB1 receptor antagonists while minimizing any risk. Indeed, CB1 receptor-neutral antagonists appear from preclinical data to offer efficacy comparable to or better than that of prototype CB1 receptor antagonists/inverse agonists, with less propensity to induce nausea. Continued pharmacological profiling, as the prelude to first-in-man testing of CB1 receptor antagonists with unique modes of targeting/pharmacological action, represents an exciting translational frontier in the critical path to CB receptor blockers as medicines.
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PMID:Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis. 1924 87

Atomoxetine (Strattera(R)) is a selective norepinephrine (noradrenaline) reuptake inhibitor that is not classified as a stimulant, and is indicated for use in patients with attention-deficit hyperactivity disorder (ADHD). Atomoxetine is effective and generally well tolerated. It is significantly more effective than placebo and standard current therapy and does not differ significantly from or is noninferior to immediate-release methylphenidate; however, it is significantly less effective than the extended-release methylphenidate formulation OROS(R) methylphenidate (hereafter referred to as osmotically released methylphenidate) and extended-release mixed amfetamine salts. Atomoxetine can be administered either as a single daily dose or split into two evenly divided doses, has a negligible risk of abuse or misuse, and is not a controlled substance in the US. Atomoxetine is particularly useful for patients at risk of substance abuse, as well as those who have co-morbid anxiety or tics, or who do not wish to take a controlled substance. Thus, atomoxetine is a useful option in the treatment of ADHD in children and adolescents. The mechanism of action of atomoxetine is unclear, but is thought to be related to its selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex. Atomoxetine has a high affinity and selectivity for norepinephrine transporters, but little or no affinity for various neurotransmitter receptors. Atomoxetine has a demonstrated ability to selectively inhibit norepinephrine uptake in humans and animals, and studies have shown that it preferentially binds to areas of known high distribution of noradrenergic neurons, such as the fronto-cortical subsystem. Atomoxetine was generally associated with statistically, but not clinically, significant increases in both heart rate and blood pressure in pediatric patients with ADHD. While there was an initial loss in expected height and weight among atomoxetine recipients, this eventually returned to normal in the longer term. Data suggest that atomoxetine is unlikely to have any abuse potential. Atomoxetine appeared less likely than methylphenidate to exacerbate disordered sleep in pediatric patients with ADHD. Atomoxetine is rapidly absorbed, and demonstrates dose-proportional increases in plasma exposure. It undergoes extensive biotransformation, which is affected by poor metabolism by cytochrome P450 (CYP) 2D6 in a small percentage of the population; these patients have greater exposure to and slower elimination of atomoxetine than extensive metabolizers. Patients with hepatic insufficiency show an increase in atomoxetine exposure. CYP2D6 inhibitors, such as paroxetine, are associated with changes in atomoxetine pharmacokinetics similar to those observed among poor CYP2D6 metabolizers. Once- or twice-daily atomoxetine was effective in the short-term treatment of ADHD in children and adolescents, as observed in several well designed placebo-controlled trials. Atomoxetine also demonstrated efficacy in the longer term treatment of these patients. A single morning dose was shown to be effective into the evening, and discontinuation of atomoxetine was not associated with symptom rebound. Atomoxetine efficacy did not appear to differ between children and adolescents. Stimulant-naive patients also responded well to atomoxetine treatment. Atomoxetine did not differ significantly from or was noninferior to immediate-release methylphenidate in children and adolescents with ADHD with regard to efficacy, and was significantly more effective than standard current therapy (any combination of medicines [excluding atomoxetine] and/or behavioral counseling, or no treatment). However, atomoxetine was significantly less effective than osmotically released methylphenidate and extended-release mixed amfetamine salts. The efficacy of atomoxetine did not appear to be affected by the presence of co-morbid disorders, and symptoms of the co-morbid disorders were not affected or were improved by atomoxetine administration. Health-related quality of life (HR-QOL) appeared to be positively affected by atomoxetine in both short- and long-term studies; atomoxetine also improved HR-QOL to a greater extent than standard current therapy. Atomoxetine was generally well tolerated in children and adolescents with ADHD. Common adverse events included headache, abdominal pain, decreased appetite, vomiting, somnolence, and nausea. The majority of adverse events were mild or moderate; there was a very low incidence of serious adverse events. Few patients discontinued atomoxetine treatment because of adverse events. Atomoxetine discontinuation appeared to be well tolerated, with a low incidence of discontinuation-emergent adverse events. Atomoxetine appeared better tolerated among extensive CYP2D6 metabolizers than among poor metabolizers. Slight differences were evident in the adverse event profiles of atomoxetine and stimulants, both immediate- and extended-release. Somnolence appeared more common among atomoxetine recipients and insomnia appeared more common among stimulant recipients. A black-box warning for suicidal ideation has been published in the US prescribing information, based on findings from a meta-analysis showing that atomoxetine is associated with a significantly higher incidence of suicidal ideation than placebo. Rarely, atomoxetine may also be associated with serious liver injury; postmarketing data show that three patients have had liver-related adverse events deemed probably related to atomoxetine treatment. Treatment algorithms involving the initial use of atomoxetine appear cost effective versus algorithms involving initial methylphenidate (immediate- or extended-release), dexamfetamine, tricyclic antidepressants, or no treatment in stimulant-naive, -failed, and -contraindicated children and adolescents with ADHD. The incremental cost per quality-adjusted life-year is below commonly accepted cost-effectiveness thresholds, as shown in several Markov model analyses conducted from the perspective of various European countries, with a time horizon of 1 year.
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PMID:Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. 1944 48

Rhabdomyolysis is a rare but potentially life-threatening disorder. The long list of known risk factors includes trauma, drug intoxication, alcoholism, hyperpyrexia, vascular occlusion, infections, electrolyte imbalances, heat intolerance, seizures, severe exertion, and substance abuse. Exercise-induced muscle damage is commonly experienced after physical activity, and different studies showed that the amount of protein consumed seems to affect its magnitude. In this regard, some concern has been raised about vegetarian athletes. We present a case of rhabdomyolysis that occurred in a young athlete following a poorly planned vegetarian diet. The athlete experienced progressive weakness and intermittent muscle aches particularly in the legs, malaise, episodic tachycardia, and nausea. Serum creatine kinase was markedly elevated (9952 units/liter), and a mild alteration of transaminase values was observed. The patient was hydrated intravenously and recovered fully within 5 days. The controlled introduction of a planned amount of protein in the diet allowed the athlete to carry on with his sporting activity fully without any further muscle problems. Physical exercise mainly engages the muscular system, and a balanced diet is essential to ensure the energy demands and the anabolic response. A vegetarian diet per se is not associated with detrimental effects in athletes, but an optimal protein intake should be achieved through careful planning with an emphasis on protein-rich plant foods.
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PMID:Rhabdomyolysis in a young vegetarian athlete. 1966 78

A healthy 19-year-old man with no history of substance abuse presented with 3 days of dyspnea and chest pressure relieved by leaning forward associated with nausea, emesis, and diarrhea. Cardiac computed tomography angiography (CCTA) showed normal coronary artery anatomy and no evidence of coronary artery plaque. The delayed-enhancement CCTA showed patchy epicardial and mid-myocardial enhancement of the wall and apex, consistent with myocardial inflammation. Delayed-enhancement cardiac magnetic resonance imaging (CMR) performed the following day confirmed patchy, diffuse epicardial hyperenhancement of the lateral wall, septum, and apex consistent with myocardial inflammation. Both CCTA and CMR supported the diagnosis of acute myocarditis. Delayed-enhancement CCTA is correlated with delayed-enhancement CMR in acute myocarditis by territory and extent and can show late hyperenhancement that can be transmural, subepicardial, or confined to small foci within a layer of the myocardium. Delayed-enhancement CCTA has potential utility for simultaneous evaluation of coronary arteries and myocardial inflammation in suspected myocarditis.
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PMID:Evaluation of myocarditis with delayed-enhancement computed tomography. 2008 62

Addictive behavior following gastric bypass surgery is widely discussed in the lay press, but published reports provide conflicting evidence regarding the prevalence of postoperative substance abuse among bariatric surgery patients. We present a case report of a Roux-en-Y gastric bypass patient who presented with recurrent and various pain and nausea complaints postoperatively. These symptoms resulted in multiple radiological and operative procedures before her narcotic addiction was identified. Physicians caring for bariatric surgical patients postoperatively need to be aware of this risk and need to be able to identify early signs of potential postoperative addictions.
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PMID:Narcotic addiction following gastric bypass surgery--a case study. 2047 21

The main pharmacological effects of marijuana, as well as synthetic and endogenous cannabinoids, are mediated through G-protein-coupled receptors (GPCRs), including CB(1) and CB(2) receptors. The CB(1) receptor is the major cannabinoid receptor in the central nervous system and has gained increasing interest as a target for drug discovery for treatment of nausea, cachexia, obesity, pain, spasticity, neurodegenerative diseases and mood and substance abuse disorders. Evidence has accumulated to suggest that CB(1) receptors, like other GPCRs, interact with and are regulated by several other proteins beyond the established role of heterotrimeric G-proteins. These proteins, which include the GPCR kinases, beta-arrestins, GPCR-associated sorting proteins, factor associated with neutral sphingomyelinase, other GPCRs (heterodimerization) and the novel cannabinoid receptor-interacting proteins: CRIP(1a/b), are thought to play important roles in the regulation of intracellular trafficking, desensitization, down-regulation, signal transduction and constitutive activity of CB(1) receptors. This review examines CB(1) receptor-interacting proteins, including heterotrimeric G-proteins, but with particular emphasis on non-G-protein entities, that might comprise the CB(1) receptosomal complex. The evidence for direct interaction with CB(1) receptors and potential functional roles of these interacting proteins is discussed, as are future directions and challenges in this field with an emphasis on the possibility of eventually targeting these proteins for drug discovery.
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PMID:Cannabinoid CB1 receptor-interacting proteins: novel targets for central nervous system drug discovery? 2059 May 57

The purpose of this study was to document the clinical and demographic characteristics of the 20 most frequent users of emergency departments (EDs) in one urban area. We reviewed administrative records from three EDs and two agencies providing services to homeless people in Baltimore City. The top 20 users accounted for 2,079 visits at the three EDs. Their mean age was 48, and median age was 51. Nineteen patients visited at least 2 EDs, 18 were homeless, and 13 had some form of public insurance. The vast majority of visits (86%) were triaged as moderate or high acuity. The five most frequent diagnoses were limb pain (n = 9), lack of housing (n = 6), alteration of consciousness (n = 6), infection with human immunodeficiency virus (HIV) (n = 5), and nausea/vomiting (n = 5). Hypertension, HIV infection, diabetes, substance abuse, and alcohol abuse were the most common chronic illnesses. The most frequent ED users were relatively young, accounted for a high number of visits, used multiple EDs, and often received high triage scores. Homelessness was the most common characteristic of this patient group, suggesting a relationship between this social factor and frequent ED use.
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PMID:Ill, itinerant, and insured: the top 20 users of emergency departments in Baltimore city. 2260 57

Obsessive-compulsive disorder (OCD) is often the anxiety disorder that affects approximately 2% of the population. This disorder is associated with significant morbidity and dysfunction, and is included in the World Health Organization list of the ten most disabling medical illnesses. The therapeutic response of patients with OCD is relatively poor compared with that of other mental disorders. Pharmacological interventions for OCD have focused on modulating primarily serotonin function and secondarily dopamine neurotransmission. Augmentation treatment has been the subject of several studies in treatment-resistant obsessive compulsive disorder (OCD). We hypothesized that medications with a dual action on the melatoninergic and serotoninergic systems may be of use in treatment-resistant OCD. In this open label study we investigated the efficacy and safety of agomelatine augmentation in treatment-resistant OCD. Twelve patients, aged 18-50, fulfilling OCD criteria, having failed to respond to adequate treatment with a Serotonine Reuptake Inhibitor for at least 16 weeks, were assigned to receive agomelatine augmentation. Subjects were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and were screened for treatment-emergent side effects at baseline and week 16 of treatment. We excluded patients with comorbid psychopathology, serious medical comorbidity, current or past history of substance abuse and severe personality disorders as well as patients receiving psychotherapy in addition to psychopharmacological treatment. Agomelatine augmentation lead to net improvement in Y-BOCS and its obsession and compulsion subscales after 16 weeks of treatment (all p<0.005). Agomelatine augmentation was well-tolerated and none of the patients dropped-out. Treatment-related adverse events were recorded as follows: (n, %): nausea: 1 (8.3%), headache 4 (33.3%), dizziness: 3 (25%) and somnolence: 2 (16.7%). The present case series study has several limitations due to its open-label design and the absence of a placebo or active control group. The small number of patients further limits the impact of our findings. The present case series study showed that a 16 week add-on treatment with agomelatine, achieved on average a 25% improvement in Y-BOCS in refractory to treatment OCD patients; side effects were mild, and none of the patients dropped out throughout the 16-week study period. Agomelatine could be efficacious and well tolerated as an augmenting agent in refractory to treatment OCD. The unique pharmacological profile of agomelatine and its dual action on serotoninergic and melatoninergic receptors may be of interest in this difficult-to-treat illness. Further controlled studies are warranted to explore the efficacy of agomelatine, as well as the potential role of circadian rhythm modulation both in the pathophysiology and treatment of OCD.
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PMID:Agomelatine augmentation in obsessive compulsive disorder: a preliminary report. 2536 61

Kratom is an unscheduled opioid receptor agonist that comes in the form of dietary supplements currently being abused by chronic pain patients on prescription opioids. Active alkaloids isolated from kratom such as mitragynine and 7-hydroxymitragynine are thought to act on mu- and delta-opioid receptors as well as alpha-2 adrenergic and 5-HT2A receptors. Animal studies suggest that kratom may be more potent than morphine. Consequently, kratom consumption produces analgesic and euphoric feelings among users. In particular, some chronic pain patients on opioids take kratom to counteract the effects of opioid withdrawal. Although the Food and Drug Administration has banned its use as a dietary supplement, kratom continues to be widely available and easily accessible on the Internet at much less expensive rates than some opioid replacement therapies like buprenorphine. There are no federal regulations monitoring the sale and distribution of this drug, yet kratom has been associated with severe signs and symptoms such as hallucinations, delusions, depressions, myalgias, chills, nausea/vomiting, respiratory hepatoxicity, seizures, coma, and death. A search of the pain literature shows past research has not described the use and potential deleterious effects of this drug. Many pain physicians are not familiar with kratom and as providers who take care of high-risk chronic pain patients using prescribed opioids, knowledge of current unregulated opioid receptor agonists with abuse potential is of paramount importance. The goal of this article is to introduce kratom to pain specialists and to spur a conversation on how pain physicians may take the lead to help curb the opioid abuse and overdose epidemic. Further studies may be required to help better understand the clinical and long-term effects of kratom use among chronic pain patients.Key words: Opioid receptor agonist, Kratom, Mitragynine, opioid overdose, chronic pain, substance abuse.
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PMID:Is Kratom the New 'Legal High' on the Block?: The Case of an Emerging Opioid Receptor Agonist with Substance Abuse Potential. 2807 12

Superior mesenteric artery (SMA) syndrome is a rare cause of small bowel obstruction (SBO) resulting from compression of the duodenum by the SMA. Patients at risk of developing SMA syndrome include those who have experienced rapid weight loss from chronic illnesses, malignancy, bariatric surgery, eating disorders, burns, trauma, or substance abuse. We present the case of a 54-year-old cachectic female patient who presented with sudden onset nausea, vomiting, and severe epigastric pain. Imaging studies revealed distention of the stomach and proximal portion of the duodenum with abrupt narrowing of the third part of the duodenum consistent with SMA syndrome. A laparoscopy confirmed the diagnosis and duodenojejunostomy resulted in resolution of the symptoms.
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PMID:Superior Mesenteric Artery Syndrome: The Dark Side of Weight Loss. 2937 45


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