Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterase (PDE) enzymes are responsible for the inactiviation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterase 4 (PDE4) is a cAMP specific phosphodiesterase expressed in inflammatory cells such as eosinophils. Inhibition of PDE4 results in an elevation of cAMP in these cells, which in turn downregulates the inflammatory response. The anti-inflammatory effects of PDE4 inhibitors have been well documented both in vitro and in vivo in a range of animal models. The potential use of PDE4 inhibitors as anti-inflammatory agents for the treatment of diseases such as asthma, chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS), has received considerable attention from the pharmaceutical industry but to date, there are no selective PDE4 inhibitors on the market. Early PDE4 inhibitors, such as rolipram suffered from dose limiting side effects, including nausea and emesis, which severely restricted their therapeutic utility. Second generation compounds such as cilomilast have been identified with reduced side effect liability. Indeed, cilomilast is showing good therapeutic effects in clinical trials for asthma and COPD and represents the most advanced selective PDE4 inhibitor for any indication. The utility of this class of inhibitor in other inflammatory diseases is less well advanced. However, data in animal models of rheumatoid arthritis (RA) and MS suggests that there is also significant potential for PDE4 inhibitors as treatments for these diseases and the results of clinical trials in these disease areas are eagerly awaited.
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PMID:Update on the therapeutic potential of PDE4 inhibitors. 1177 17

Substance P (SP) is a neuropeptide which is abundant in the periphery and the central nervous system, where it is colocalized with other neurotransmitters such as serotonin or dopamine. SP has been proposed to play a role in the regulation of pain including migraine and fibromyalgia, asthma, inflammatory bowel disease, emesis, psoriasis as well as in central nervous system disorders. This review summarizes our current knowledge of the role of SP in the pathogenesis of neuropsychiatric disorders with special emphasis on affective disorders including bipolar disorders. It also reviews current treatment approaches with neurokinin 1 receptor antagonists which appear to be promising drugs for the future treatment of affective disorders.
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PMID:Substance P and affective disorders: new treatment opportunities by neurokinin 1 receptor antagonists? 1189 70

The association between gastroesophageal reflux (GER) and asthma is not fortuitous. The objective of our study was to test a group of children with asthma by, 24 hr gastroesophageal pH monitoring and to relate the results to the patients medical history and clinical data. We studied 77 children aged from 39 to 170 months suffering from particularly recurrent and/or therapy-resistant asthma. Medical history data were collected for each patient and included: severity and characteristics of respiratory symptoms, presence, if any of allergy; presence, if any, of GER-related symptoms; and presence, if any, of esophagitis-related symptoms. Esophageal pH was measured by 24 hr computerized monitoring of the main measures in all patients. Forty-seven children were also examined by gastroesophageal endoscopy. The prevalence of GER was 61% on the basis of the reflux index (cutoff: 4.2%). Gastroesophageal reflux in these asthmatic children was characterized mainly by short-lasting daytime episodes. The patients tended to present GER mainly associated with vomiting but not with signs and symptoms of esophagitis. The short-lasting nature of the reflux episodes demonstrates good esophageal clearance. The time of onset of respiratory symptoms (day/night) was not associated with any particular type of GER, the severity of which tends to be proportional to the seriousness of the asthma. No correlation was found between GER and allergy. No statistically significant differences were found in clinical or medical history findings between patients with pathologic and nonpathologic GER.
J Asthma 2002 Apr
PMID:The pattern of gastroesophageal reflux in asthmatic children. 1199 Feb 28

Phosphodiesterase 4 (PDE4) is a major cyclic adenosine-3',5'-monophosphate-metabolizing enzyme in immune and inflammatory cells, airway smooth muscle, and pulmonary nerves. Selective inhibitors of this enzyme have been available for a number of years and show a broad spectrum of activity in animal models of COPD and asthma. The class-associated side effects, mainly nausea and emesis, appear to have been at least partially overcome by the so-called "second-generation" PDE4 inhibitors. Currently, three companies are in the later stages of development of candidate second-generation PDE4 inhibitors for the treatment of COPD patients. The preclinical profile of one of these, BAY 19-8004, is summarized below. The initial clinical data on the most advanced compound, cilomilast, were indeed encouraging. However, full knowledge of the therapeutic value of this novel compound class awaits the outcome of longer term clinical trials.
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PMID:Phosphodiesterase 4 inhibitors for the treatment of COPD. 1201 Aug 50

The phosphodiesterases (PDEs) are responsible for the hydrolysis of intracellular cyclic adenosine and guanosine monophosphate (cAMP and cGMP, respectively). They are classified into 11 major families (PDE1-11) and the type 4 phosphodiesterase (PDE4) is a cAMP-specific enzyme localized in airway smooth muscle cells as well as in immune and inflammatory cells. The PDE4 activity is associated with a wide variety of diseases some of which have been related to an inflammatory state, (e.g. asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA)) while others have recently been connected to autoimmune pathology. Therefore, an intense effort toward the development of PDE4 inhibitors has been generated for the last decade. Unfortunately, the effects of prototype PDE4 inhibitors have been compromised by side effects such as nausea and emesis and the clinical use of those compounds is still limited. Several companies have focused on the design of a new generation of PDE4 inhibitors dissociating beneficial activity and adverse effects. This review highlights the recent data of the most advanced clinical candidates, the design and structure activity relationships of the recent structural series reported in the literature over the last two years, as well as recent advances in the multiple therapeutic indications of PDE4 inhibitors (a review with 375 references).
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PMID:Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs. 1205 19

N-(3,5-Dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 351591) has been identified as a potent (IC(50) = 58 nM) and highly selective type 4 phosphodiesterase (PDE4) inhibitor with oral bioactivity in several animal models of lung inflammation. N-(3,5-Dichloro-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 365351), the only significant in vivo metabolite, is also a potent and highly selective PDE4 inhibitor (IC(50) = 20 nM). Both SCH 351591 and SCH 365351 inhibited cytokine production in human blood mononuclear cell preparations. Oral SCH 351591 significantly attenuated allergen-induced eosinophilia and airway hyperreactivity in allergic guinea pigs at doses as low as 1 mg/kg. In this model, oral SCH 365351 showed similar potency. When SCH 351591 was administered orally to allergic cynomolgus monkeys at 3 mg/kg, Ascaris suum-induced lung eosinophilia was blocked. Hyperventilation-induced bronchospasm in nonallergic guinea pigs, a model for exercise-induced asthma, was also suppressed significantly by oral SCH 351591 at 0.3 mg/kg. Cilomilast (SB 207499; Ariflo), a PDE4 inhibitor currently being developed for asthma and chronic obstructive pulmonary disease (COPD), was 10- to 30-fold less potent than SCH 351591 at inhibiting guinea pig lung eosinophilia and hyperventilation-induced bronchospasm. In a ferret model of emesis, maximum nonemetic oral doses of SCH 351591 and cilomilast were 5 and 1 mg/kg, respectively. Comparison of plasma levels at these nonemetic doses in ferrets to those at doses inhibiting hyperventilation-induced bronchospasm in guinea pigs gave a therapeutic ratio of 16 for SCH 351591 and 4 for cilomilast. Thus, SCH 351591 exhibits a promising preclinical profile as a treatment for asthma and COPD.
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PMID:Pharmacology of N-(3,5-dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 351591), a novel, orally active phosphodiesterase 4 inhibitor. 1206 9

The management of dementia patients encompasses pharmacologic, behavioral, and psychosocial intervention strategies. Before pharmacologic intervention is instituted, it is important that sources of excess disability and comorbidity be eliminated or reduced. Identification of comorbid medical and psychiatric conditions, such as depression and delirium, should be identified and appropriately treated. Providing caregivers with education, support, and practical advice is a critical component of the management of the demented patient. The current standard of care for pharmacologic management of the cognitive and functional disabilities of AD consists of the combination of a cholinesterase inhibitor and high-dose vitamin E. This standard is based on the results of large-scale, double-blind, placebo-controlled trials. Cholinesterase inhibitors are the only FDA-approved pharmacologic treatments for AD. Cholinesterase inhibitors have been shown to be effective in the treatment of the cognitive, behavioral, and functional deficits of AD. Large-scale placebo-controlled trials of tacrine, donepezil, rivastigmine, and galantamine have demonstrated moderate benefits in patients with mild to moderate AD. Donepezil, rivastigmine, and galantamine are the first-line choices in the treatment of AD because of their lack of hepatotoxicity, ease of administration, few significant drug-drug interactions, and mild to moderate side effects. There are few contraindications to the use of cholinesterase inhibitors. Known hypersensitivity to a specific drug or its derivatives is the only true contraindication. Cautious administration of cholinesterase inhibitors is advised in patients who have a previous history of allergy or adverse reactions to prior cholinesterase inhibitors, severe liver disease, preexisting bradycardia, peptic ulcer disease, current alcoholism, asthma, or chronic obstructive pulmonary disease. Nausea, vomiting, diarrhea, and anorexia are the most common side effects of cholinesterase inhibitors. These gastrointestinal side effects can be minimized by gradual dose increases, administration with food, adequate hydration, and judicious use of an antiemetic. Vitamin E has been demonstrated to slow the progression of AD in several small and one large placebo-controlled trials. Because of its low cost and safety, it is recommended in addition to a cholinesterase inhibitor for the treatment of AD. There are no FDA-approved treatments for DLB and VaD. One small placebo-controlled trial demonstrated that rivastigmine may be effective in the treatment of DLB. More large-scale placebo-controlled trials are needed to confirm the results of this study. Treatment of VaD focuses on the control, identification, and management of cerebrovascular disease and vascular risk factors. Although there are no peer-reviewed reports on the efficacy of cholinesterase inhibitors for VaD or mixed AD/VaD, early reports suggest that these agents may also be effective for mixed AD/VaD. The indications for the use of cholinesterase inhibitor drugs are eventually likely to broaden to include DLB, mixed AD/VaD, and AD in its more advanced stages.
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PMID:Pharmacologic treatments of dementia. 1217 Oct 61

Vomiting, the culminating sign of nausea, is primarily a protective reflex occurring in a wide variety of vertebrates. Even tough nausea and vomiting are among the most basic neural reflexes, they remain poorly understood. Poorly understood are the pathogenetic mechanisms from the anatomic receptor and neuroendocrine point of view. This is the reason why drugs are useful in some types of vomiting but not in others. The aim of this paper is to summarize current knowledge about anatomy of vomiting reflex, neurotransmitter receptor subtypes, agonists and antagonists of serotonin and substance P. Particularly in the treatment of post-chemotherapy and postoperative vomiting. It is pointed out that nausea an vomiting may be field of neurochemical and neuropharmacological research. Finally, in clinical research drugs for vomiting therapy may be useful in other pathologies (migraine, rheumatoid arthritis, bronchial asthma).
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PMID:[Vomiting]. 1220 99

In several ancient systems of medicine including Ayurveda, Greek, Roman, Siddha and Unani, Ocimum sanctum has vast number of therapeutic applications such as in cardiopathy, haemopathy, leucoderma, asthma, bronchitis, catarrhal fever, otalgia, hepatopathy, vomiting, lumbago, hiccups, ophthalmia, gastropathy, genitourinary disorders, ringworm, verminosis and skin diseases etc. The present review incorporates the description of O. sanctum plant, its chemical constituents, and various pharmacological activities.
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PMID:Validation of traditional claim of Tulsi, Ocimum sanctum Linn. as a medicinal plant. 1259 45

Three children presented with adrenal crises, manifested by vomiting and hypoglycaemia, after protracted courses of high-dose inhaled corticosteroids for asthma. Significant dose reduction was possible in all three without loss of asthma control, emphasising the importance of back-titration to minimise dose. Parents of children taking high doses of inhaled corticosteroids should be alerted to the clinical features of adrenal insufficiency. If suspected, prompt medical assessment should be arranged, including serum glucose and cortisol measurement.
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PMID:Adrenal crises in children treated with high-dose inhaled corticosteroids for asthma. 1288 75


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