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At least 1,423 records · Page 79Linked to original sources

PubMed2000

Changes in mesenteric blood flow response to feeding: conventional versus fiber-optic phototherapy.

OBJECTIVE: To evaluate whether fiberoptic phototherapy influences the postprandial increase in mesenteric blood flow velocity similarly to conventional phototherapy in preterm infants. PATIENTS AND METHODS: With the use of Doppler color ultrasonography, blood flow velocity in the superior mesenteric artery was measured both preprandially and postprandially in 19 preterm infants during and after conventional phototherapy, and in 20 preterm infants during and after fiber-optic phototherapy. The mean arterial blood pressure/mean flow velocity ratio was calculated as an estimate of relative vascular resistance of the superior mesenteric artery. RESULTS: The study shows that conventional phototherapy blunts the postprandial mesenteric blood flow response to feeding in preterm infants. Furthermore, it shows that the postprandial increase in intestinal blood flow is not attenuated when fiber-optic phototherapy is administered, and that such postprandial increase of blood flow is significantly greater than in infants receiving conventional phototherapy. During and after fiber-optic phototherapy, a significant reduction in postprandial relative vascular resistance was found; such reduction was significantly greater than during conventional phototherapy. CONCLUSIONS: Fiber-optic phototherapy is preferable to conventional phototherapy for the treatment of hyperbilirubinemia in preterm infants because it does not affect the physiologic postprandial redistribution of blood flow from the periphery to the gastrointestinal system as does conventional phototherapy.

Blood Flow Velocity↗

PubMed2002

Discomfort: not pain but still unpleasant feelings from the gut.

Most of the factors initiating food or fluid intake have already been studied, but much less is known about those terminating ingestion. We have hypothesised that discomfort originating from the gastrointestinal system may be one of those factors. Gut distension cause pain if the intestinal volume changes but merely discomfort if only the tension of the gut wall increases. It seems that mild unpleasantness (i.e. discomfort) arising from the gut as a result of moderate (quasi-isometric) distension, among and in concordance with other factors, may significantly reduce intake and hence contribute to physiological satiety. The arising discomfort can be detected by measuring the amount and rate of the ingestion, by recording and analysing ingestive behavior by taste-aversivity and taste-reactivity tests, etc. Conclusions of all experiments point to the same direction: tension increase in the gut wall causes discomfort and results in decrease of intake, i.e. satiety.

Animals↗

PubMed2005

Endoscopic ultrasonography in the diagnosis and management of cancer.

Since its development and introduction to clinical practice, endoscopic ultrasonography (EUS) has progressed rapidly from being a purely imaging modality with limited use in the detection of small pancreatic cancers to one that can provide a tissue diagnosis by fine-needle aspiration (FNA) and deliver therapy. EUS has now firmly established a place as the investigation of choice in the diagnosis, locoregional staging and management of a wide range of gastrointestinal cancers. With the increasing use of FNA, the accuracy of EUS has substantially improved and may become a stand-alone investigation in some situations. However, it is recommended that a combination of information obtained from other imaging modalities and EUS is needed to maximize the accuracy, in particular to complete staging beyond locoregional stage. In addition to well-established indications, newer applications of EUS are emerging and are no longer limited to the gastrointestinal system. In lung cancer, EUS combined with endobronchial ultrasonography is emerging as an accurate, minimally invasive, nonsurgical alternative to staging of the mediastinum. Furthermore, the ability of EUS to acquire tissue safely and conveniently results in a potential role of the molecular diagnostics to enhance the performance of EUS-guided FNA. Besides a diagnostic role of EUS, there continues to be technological advances in the field of interventional EUS, with many potential applications under investigation. This review focuses on the current and future roles of EUS in the diagnosis and management of cancers.

Animals↗

PubMed2004

Telithromycin.

Telithromycin (Ketek), Aventis Pharma), a ketolide, belongs to a new class of antibiotics that was developed for the treatment of upper and lower respiratory tract infections. The prevalence of penicillin and macrolide resistance among respiratory pathogens is increasing in the USA. Telithromycin is highly active against beta-lactam, macrolide and fluoroquinolone reduced-susceptibility pathogens. Its efficacy has been shown to be equal or superior to comparator agents in numerous studies. It has a broad in vitro spectrum versus usual respiratory pathogens and oral once-daily dosing that increases patient compliance. Telithromycin penetrates rapidly into neutrophils in bronchopulmonary tissue, with peak levels obtained in 1 to 2 h. Results of clinical trials show clinical-esponse rates similar to comparator agents. The most frequent adverse events involve the gastrointestinal system, with mild to moderate diarrhea and nausea. A low rate of discontinuation was observed in the studies. Telithromycin is an effective first-line treatment for mild to moderate respiratory infections in adults.

Anti-Bacterial Agents↗

PubMedDate not supplied

[Aspects of sleep effects on the digestive tract].

BACKGROUND: During sleep the gastrointestinal system function is markedly reduced most of the time. OBJECTIVES: In this revision we described the effect of sleep on the digestive system. Salivation, swallowing rate, upper esophageal sphincter pressure and number of primary esophageal contractions have all been shown to be reduced during sleep. DATA SOURCES: Gastric emptying is slow during sleep but the REM sleep is associated with faster gastric emptying. During the night we have a more regular intestinal motility than during the day. During sleep, phase II of the migrating motor complex cycle is virtually absent, both during diurnal or nocturnal sleep. The nocturnal velocity of migrating motor complex propagation in the proximal small bowel is slower than the diurnal velocity. The colon has a decrease in tonus and contractions. The anal canal pressure is lower and rectum activity is higher during sleep than during the awake state, but the anal pressure is still higher than the rectum pressure and the rectum contractions are most frequently retrograde. DATA SYNTHESIS: Transient lower esophageal sphincter relaxation is the most frequent cause of gastroesophageal reflux. The frequency of this transient relaxation is very low during sleep. Gastroesophageal reflux during sleep is more frequently associated with a low lower esophageal sphincter pressure. CONCLUSIONS: In this situation the disease is worse because the patient is in the supine position, so gravity does not help the acid esophageal clearance, salivation is decreased and the primary esophageal contraction is not frequent, a fact causing a prolongation of acid clearance during sleep. The right lateral position during sleep causes more reflux episodes than the left lateral position. The gastroesophageal reflux may be associated with nocturnal wheezing, chronic nocturnal cough and sleep apnea.

Digestive System Physiological Phenomena↗

PubMed2005

Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation.

The symptomatic phases of many inflammatory diseases are characterized by migration of large numbers of neutrophils (PMN) across a polarized epithelium and accumulation within a lumen. For example, acute PMN influx is common in diseases of the gastrointestinal system (ulcerative colitis, Crohn's disease, bacterial enterocolitis, gastritis), hepatobiliary system (cholangitis, acute cholecystitis), respiratory tract (bronchial pneumonia, bronchitis, cystic fibrosis, bronchiectasis), and urinary tract (pyelonephritis, cystitis). Despite these observations, the molecular basis of leukocyte interactions with epithelial cells is incompletely understood. In vitro models of PMN transepithelial migration typically use N-formylated bacterial peptides such as fMLP in isolation to drive human PMNs across epithelial monolayers. However, other microbial products such as lipopolysaccharide (LPS) are major constituents of the intestinal lumen and have potent effects on the immune system. In the absence of LPS, we have shown that transepithelial migration requires sequential adhesive interactions between the PMN beta2 integrin CD11b/CD18 and JAM protein family members. Other epithelial ligands appear to be abundantly represented as fucosylated proteoglycans. Further studies indicate that the rate of PMN migration across mucosal surfaces can be regulated by the ubiquitously expressed transmembrane protein CD47 and microbial-derived factors, although many of the details remain unclear. Current data suggests that Toll-like receptors (TLR), which recognize specific pathogen-associated molecular patterns (PAMPs), are differentially expressed on both leukocytes and mucosal epithelial cells while serving to modulate leukocyte-epithelial interactions. Exposure of epithelial TLRs to microbial ligands has been shown to result in transcriptional upregulation of inflammatory mediators whereas ligation of leukocyte TLRs modulate specific antimicrobial responses. A better understanding of these events will hopefully provide new insights into the mechanisms of epithelial responses to microorganisms and ideas for therapies aimed at inhibiting the deleterious consequences of mucosal inflammation.

Cell Movement↗

PubMed2005

[Prospective, randomized and controlled trial on the dwell time of peripheral intravenous catheters in children, according to three dressing regimens].

This prospective, randomized and controlled study verified the influence of three dressing regimens on the dwell time of peripheral intravenous catheters (PIC) in children. The study groups were composed of dressings with sterile gauze (EG 1), with sterile transparent film (EG 2) and with hypoallergenic adhesive tape (CG). Variables were selected to control for variables related to children, professionals and intravenous therapy characteristics. The 150 PIC that composed the sample were inserted in 68 children, predominantly of preschool age, male, with brown skin color, eutrophic and with gastrointestinal system diseases. The majority of the PIC was installed by nursing auxiliaries in veins of the dorsal arch of the hand. The type of dressing exerted a significant influence (p = 0.022) on the average dwell time of the studied PIC: EG 1 (46.12 hours), EG 2 (29.53 hours) and CG (38.18 hours), concluding that the dressing with sterile gauze maintained the catheter inserted for a longer time.

Bandages↗

PubMed1999

Medical options for treating Crohn's disease in adults: focus on antitumor necrosis factor-alpha chimeric monoclonal antibody.

Crohn's disease is a chronic inflammatory disorder that can present with symptoms throughout the gastrointestinal system. Though the etiology of Crohn's disease is unknown, genetic and environmental factors seem to play a role. An imbalance of proinflammatory versus antiinflammatory cytokines is responsible for many of the symptoms. Tumor necrosis factor alpha, a potent proinflammatory cytokine, plays a particularly important role. Several treatment modalities for Crohn's disease exist, recently including antitumor necrosis factor chimeric monoclonal antibody (cA2). Treatment for Crohn's disease, including data on the safety and efficacy of cA2, will be reviewed.

Adult↗

PubMed2005

Ghrelin against alendronate-induced gastric damage in rats.

Alendronate sodium, a primary amino bisphosphonate, is widely used in the treatment of various diseases that are associated with bone resorption, such as postmenopausal osteoporosis and Paget's disease of bone. Although the adverse effects of biphosphonates on the gastrointestinal system have been demonstrated in experimental and clinical studies, the exact mechanisms underlying this damage are not clear yet. Ghrelin, a 28 amino acid peptide produced predominantly by the stomach, was shown to exert a potent protective action on the stomach of rats exposed to ethanol or stress. Our objective was to evaluate the possible anti-oxidant and anti-inflammatory effects of ghrelin against alendronate-induced gastric damage. Wistar albino rats were administered alendronate (20 mg/kg) by gavage for 4 days, along with either ghrelin (10 ng/kg per day) or saline given i.p. After decapitation, stomach tissues were removed for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and tissue collagen content, while the extent of tissue damage was analyzed microscopically. Formation of reactive oxygen species was determined by chemiluminesence using a luminol probe in fresh gastric tissues. Serum tumor necrosis factor (TNF-alpha) and lactate dehydrogenase levels were assessed in trunk blood. Oral administration of alendronate-induced significant gastric damage, accompanied by increased MPO activity, collagen content, MDA and luminol levels (P < 0.01-P < 0.001), while tissue GSH was decreased (P < 0.01). On the other hand, ghrelin treatment reversed these alterations (P < 0.05-P < 0.001) as well as elevating serum TNF-alpha levels significantly (P < 0.001). The findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect, and ghrelin ameliorates this damage by its possible antioxidant and anti-inflammatory properties.

Administration, Oral↗

PubMed2000

A risk-benefit assessment of the newer oral antifungal agents used to treat onychomycosis.

The newer antifungal agents itraconazole, terbinafine and fluconazole have become available to treat onychomycosis over the last 10 years. During this time period these agents have superseded griseofulvin as the agent of choice for onychomycosis. Unlike griseofulvin, the new agents have a broad spectrum of action that includes dermatophytes, Candida species and nondermatophyte moulds. Each of the 3 oral antifungal agents, terbinafine, itraconazole and fluconazole, is effective against dermatophytes with relatively fewer data being available for the treatment of Candida species and nondermatophyte moulds. Itraconazole is effective against Candida onychomycosis. Terbinafine may be more effective against C. parapsilosis compared with C. albicans; furthermore with Candida species a higher dose of terbinafine or a longer duration of therapy may be required compared with the regimen for dermatophytes. The least amount of experience in treating onychomycosis is with fluconazole. Griseofulvin is not effective against Candida species or the nondermatophyte moulds. The main use of griseo-fulvin currently is to treat tinea capitis. Ketoconazole may be used by some to treat tinea versicolor with the dosage regimens being short and requiring the use of only a few doses. The preferred regimens for the 3 oral antimycotic agents are as follows: itraconazole - pulse therapy with the drug being administered for 1 week with 3 weeks off treatment between successive pulses; terbinafine - continuous once daily therapy; and fluconazole - once weekly treatment. The regimen for the treatment of dermatophyte onychomycosis is: itraconazole - 200mg twice daily for I week per month x 3 pulses; terbinafine - 250 mg/day for 12 weeks; or, fluconazole - 150 mg/wk until the abnormal-appearing nail plate has grown out, typically over a period of 9 to 18 months. For the 3 oral antifungal agents the more common adverse reactions pertain to the following systems, gastrointestinal (for example, nausea, gastrointestinal distress, diarrhoea, abdominal pain), cutaneous eruption, and CNS (for example, headache and malaise). Each of the new antifungal agents is more cost-effective than griseofulvin for the treatment of onychomycosis and is associated with high compliance, in part because of the shorter duration of therapy. The newer antifungal agents are generally well tolerated with drug interactions that are usually predictable.

Administration, Oral↗

PubMed2004

Safety profile of tegaserod, a 5-HT4 receptor agonist, for the treatment of irritable bowel syndrome.

This article reviews the safety and tolerability profile of tegaserod, a novel selective partial agonist of the serotonin 5-HT(4) receptor. Tegaserod was recently approved for the treatment of women with irritable bowel syndrome (IBS) with constipation. Tegaserod exhibits rapid absorption from the small intestine, and is excreted unchanged in the faeces and as metabolites in the urine. Meal ingestion decreases its bioavailability. There is little effect of age or gender on pharmacokinetics, although plasma levels may be slightly higher in the elderly. Tegaserod has no effect on plasma levels of other drugs metabolised by cytochrome P450 enzyme systems. Gastrointestinal symptoms are the most common adverse effects of tegaserod therapy. In data pooled from phase III randomised controlled trials (RCTs) in IBS with constipation patients, diarrhoea was reported by 8.8% of patients treated with tegaserod 6mg twice daily versus 3.8% of patients receiving placebo. Similar rates have been observed in international post-US marketing RCTs. In most patients, tegaserod-induced diarrhoea was mild and transient. In RCTs, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of IBS patients discontinued tegaserod due to diarrhoea. Since its release, rare cases of more severe diarrhoea and ischaemic colitis have been reported. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea, and flatulence) has been similar among tegaserod-treated patients and placebo-treated patients. Pooled analysis of phase III RCTs and post-US marketing RCTs have not demonstrated significant differences between tegaserod-treated patients and placebo-treated patients in the incidence of abdominal-pelvic surgery. There is no convincing evidence that rebound gastrointestinal symptoms occur upon termination of tegaserod therapy. Pooled analysis of phase III RCTs demonstrated an increase in the incidence of headaches among tegaserod-treated patients (6mg twice daily) compared with placebo-treated patients (15% vs 12.3%, respectively, p < 0.05), although post-US marketing RCTs have not observed this increase. Other extra-gastrointestinal adverse events occur with similar frequency among tegaserod-treated patients and placebo-treated patients. Tegaserod-treated patients in RCTs have not demonstrated significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. Supra-therapeutic doses in healthy volunteers did not effect electrocardiographic parameters. Laboratory parameters are mostly unaffected by tegaserod, although several individuals have exhibited increased eosinophil counts. In summary, tegaserod exhibits a favourable safety and tolerability profile in IBS patients based on data from clinical trials. Diarrhoea is the most common adverse event associated with tegaserod use. Continued post-US marketing surveillance will further define the safety and tolerability profile of tegaserod.

Drug Interactions↗

PubMed2005

Management issues with elderly-onset rheumatoid arthritis: an update.

Elderly-onset rheumatoid arthritis (EORA) is defined as rheumatoid arthritis (RA) starting at >60 years of age. EORA is characterised by a lower female/male ratio compared with RA in younger patients and it more frequently has an acute onset accompanied by constitutional symptoms. Two incompletely overlapping subsets of RA have been recognised: one exhibits the classical RA clinical picture while the other has a polymyalgia rheumatica-like appearance, characterised by shoulder involvement, absence of rheumatoid factor and, usually, by a nonerosive course. Identification of anti-cyclic citrullinated peptide antibodies is useful for distinguishing the latter subset from true polymyalgia rheumatica. Elderly-onset spondyloarthritis, crystal-related arthritis, remitting seronegative symmetrical synovitis with pitting oedema syndrome and hepatitis C virus-related arthritis must also be considered in the differential diagnosis. EORA treatment requires prudence because of the increase in age-related risks pertaining principally to the renal, cardiovascular and gastrointestinal systems. No groups of molecules usually employed for RA therapy in younger subjects (analgesics, NSAIDs, corticosteroids, disease-modifying antirheumatic drugs, anticytokine drugs) can be excluded a priori from the treatment of EORA patients. Nevertheless, the risk/benefit ratio relating to their use must be accurately evaluated for every single patient. Recently marketed compounds such as leflunomide and tumour necrosis factor-alpha antagonists have also increased the therapeutic opportunities for aged RA patients.

Aged↗

PubMed2005

Xerostomia secondary to Sjögren's syndrome in the elderly: recognition and management.

Xerostomia is a common symptom in the elderly population. Studies have suggested that the underlying cause of approximately 40% of xerostomia in the elderly is Sjögren's syndrome. Although it is highly prevalent among middle-aged individuals, elderly patients account for up to 20% of Sjögren's syndrome cases. Sjögren's syndrome is a multisystem exocrinopathy characterised by dry mouth and dry eyes with wide-ranging extraglandular involvement. The exocrine manifestations of Sjögren's syndrome affect the mouth, eyes, nose, ears, skin, vagina and the entire respiratory and gastrointestinal systems. The nonexocrine involvement may include the joints, thyroid gland, liver, kidneys and the musculoskeletal, vascular and central nervous systems. Currently, the mechanism(s) of development and progression of Sjögren's syndrome is/are not clear. Inflammation and lymphocytic infiltration of the exocrine glands is a classical feature of Sjögren's syndrome. During the progression of the disease, the acinar cells of the exocrine glands are replaced by fibrosis, rendering the glands nonfunctional. Sjögren's syndrome remains one of the most underdiagnosed conditions, particularly in the elderly population, because the cardinal sicca symptoms, which are the hallmark of the disease, are frequently attributed to aging and/or medications, which consequently delays the diagnosis. This delay in diagnosis imposes significant physical, psychological and economic burdens on elderly patients. The diagnosis of Sjögren's syndrome requires evaluation of both the exocrine and nonexocrine components of the disease. Management of Sjögren's syndrome requires collaboration by the primary-care physician, rheumatologist, ophthalmologist and dentist. This article reviews current understanding of the clinical manifestations, diagnosis and treatment of Sjögren's syndrome with special emphasis on the oral component of the disease.

Aged↗

PubMed2003

Clinical pharmacokinetic profile of modafinil.

Modafinil is a unique wake-promoting agent for oral administration. Its pharmacological properties are distinct from those of other CNS agents, and it selectively targets neuronal pathways in the sleep/wake centres of the brain. After single or multiple oral doses, modafinil is readily absorbed, reaching maximum plasma concentrations at 2-4 hours after administration and pharmacokinetic steady state within 2-4 days. Its pharmacokinetics are dose-independent between 200 and 600 mg/day. The elimination half-life is approximately 12-15 hours, which is largely reflective of the pharmacokinetics of the longer-lived l-enantiomer. Modafinil is primarily eliminated via metabolism, mainly in the liver, with subsequent excretion in the urine. Less than 10% of the dose is excreted as unchanged drug. Metabolism is largely via amide hydrolysis, with lesser contributions from cytochrome P450 (CYP)-mediated oxidative pathways. In patients who are renally or hepatically compromised, the elimination processes can be slowed, and in a similar manner (although to a lesser extent), elimination in the elderly may be reduced due to normal effects of aging. Because modafinil is administered concomitantly with other medications, the potential for metabolic drug-drug interactions has been examined both in vitro and in vivo. In vitro, modafinil was observed to produce a reversible inhibition of CYP2C19 in human liver microsomes. It also caused a small, but concentration-dependent, induction of CYP1A2, CYP2B6 and CYP3A4 activities and suppression of CYP2C9 activity in primary cultures of human hepatocytes. Clinical studies have been conducted to examine the potential for interactions with methylphenidate, dexamfetamine, warfarin, ethinylestradiol and triazolam. The only substantive interactions observed were with ethinylestradiol and triazolam, apparently through induction of CYP3A4, primarily in the gastrointestinal system. Overall, the results of the interaction studies suggest that modafinil has potential to affect the pharmacokinetics of drugs that are metabolised by certain CYP enzymes. Compounds that induce or inhibit CYP activity are unlikely to have major effects on the pharmacokinetics of modafinil. In summary, the results show that modafinil is a moderately long-lived drug that is well absorbed and extensively metabolised.

Aged↗

PubMed1998

Raltitrexed. A review of its pharmacological properties and clinical efficacy in the management of advanced colorectal cancer.

Raltitrexed (ZD-1694) is a quinazoline-based folate analogue that exerts its cytotoxic activity by the specific inhibition of thymidylate synthase. In vitro studies show that raltitrexed is actively transported into cells and is then rapidly and extensively metabolised to a series of polyglutamates. These metabolites are significantly more potent inhibitors of thymidylate synthase than the parent drug and are retained intracellularly, producing prolonged cytotoxic effects without the need for continuous drug exposure. Phase III clinical trials in patients with advanced colorectal cancer evaluated raltitrexed 3 mg/m2 administered as a 15-minute intravenous infusion once every 3 weeks. This schedule produced objective response rates of 14.3 to 19.3%, which were similar to those in patients treated with fluorouracil plus leucovorin (15.2 to 18.1%). Median survival durations ranged from 9.7 to 10.9 months with raltitrexed treatment and from 10.2 to 12.7 months with fluorouracil plus leucovorin. The major toxicities associated with raltitrexed involve the haematological and gastrointestinal systems, although severe asthenia also occurred in 6 to 18% of patients receiving the drug. Grade 3 or 4 nausea or vomiting occurred in up to 13% of raltitrexed recipients and grade 3 or 4 diarrhoea in up to 14%. Similar incidences of grade 3 or 4 nausea or vomiting and diarrhoea were seen with fluorouracil plus leucovorin treatment. Raltitrexed generally showed significant advantages over fluorouracil plus leucovorin with respect to the incidence of leucopenia and mucositis. A greater proportion of raltitrexed than fluorouracil plus leucovorin recipients were able to receive the scheduled dosage. Thus, with its similar efficacy to fluorouracil-based regimens, convenient administration schedule and favourable tolerability profile, raltitrexed provides clinicians with a worthwhile alternative to fluorouracil-based treatment for patients with advanced colorectal cancer.

Antimetabolites, Antineoplastic↗

PubMed2000

Galantamine: a review of its use in Alzheimer's disease.

UNLABELLED: Currently, acetylcholinesterase (AChE) inhibitors are the most promising class of drugs for the treatment of Alzheimer's disease (AD). Galantamine is a reversible, competitive, tertiary alkaloid AChE inhibitor. The drug is selective for AChE rather than butyrylcholinesterase. In addition to inhibition of AChE galantamine interacts allosterically with nicotinic acetylcholine receptors to potentiate the action of agonists at these receptors. Recipients of galantamine 16 or 24 mg/day achieved significant improvements in cognitive and global symptoms relative to placebo recipients in large (n = 285 to 978 patients with mild to moderate AD) well-designed trials of 3 to 6 months' duration. Galantamine also improved activities of daily living in these patients and significantly reduced the requirement for caregiver assistance with activities of daily living. Moreover, galantamine recipients achieved significantly better outcomes on behavioural symptoms than placebo recipients. In a long term study (12 months), galantamine 24 mg/day slowed the progression of symptoms of the disease and maintained cognitive function and activities of daily living in patients with mild to moderate AD. Galantamine was generally well tolerated with the majority of adverse events being mild to moderate in intensity and transient. Predictably, adverse events were cholinergic in nature and generally related to the gastrointestinal system. These effects were reduced in patients receiving the recommended dose escalation regimen. Galantamine had no clinically relevant effects on vital signs, haematological or biochemical laboratory parameters and, importantly, there were no reports of hepatotoxicity. The incidence of serious adverse events was similar between galantamine (8 to 32 mg/day) and placebo groups (6 to 16% of patients across all treatment groups). CONCLUSIONS: Galantamine is an effective well tolerated symptomatic treatment for AD which improves cognition, function and activities of daily living in the short term (up to 6 months) in patients with mild to moderate AD. In addition, it delays the development of behavioural disturbances and psychiatric symptoms, and reduces caregiver burden (as measured by caregiver time). In the long term (up to 1 year), galantamine maintains cognition and activities of daily living. Adverse events associated with galantamine are mainly cholinergic, usually mild to moderate in intensity and transient. Galantamine has been evaluated in several large well-designed studies and, given the relative lack of established treatment options, it may be considered as one of the first-line pharmacological treatments in patients with mild to moderate AD.

Acetylcholinesterase↗

PubMed2002

Spotlight on fluvoxamine in anxiety disorders in children and adolescents.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which may be used for the management of anxiety disorders in children and adolescents. Absorption of fluvoxamine was similar in adolescents to that in adults, which suggests that the maximum dosage of the drug for patients aged between 12 and 17 years can be as high as 300 mg/day. However, steady-state plasma fluvoxamine concentrations were 2 to 3 times higher in children (aged between 6 and 11 years) than in adolescents; thus, the maximum fluvoxamine dosage recommended for children is 200 mg/day. Fluvoxamine (50 to 300 mg/day) for 8 to 16 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) [measured across multiple assessment scales] compared with placebo in a well controlled trial in paediatric patients (n = 120) or from baseline in noncomparative trials in adolescent (n = 20) or paediatric (n = 16) patients. Improvements with fluvoxamine (up to 200 mg/day) were observed for up to 1 year in 98 patients with OCD in a noncomparative trial. The drug (up to 250 or 300 mg/day) also improved symptoms of anxiety compared with placebo in an 8-week well controlled trial in 128 paediatric patients with social phobia, separation anxiety disorder or generalised anxiety disorder (GAD). Fluvoxamine (50 to 300 mg/day) appears to be well tolerated in paediatric patients, with most adverse events with the drug (except abdominal discomfort, which occurred more often in patients receiving fluvoxamine) occurring with a similar incidence to those with placebo. The most common adverse events involved the CNS or gastrointestinal system. Most adverse events reported by paediatric patients with OCD were similar to those reported by adults. In conclusion, fluvoxamine is generally well tolerated and has demonstrated short-term efficacy compared with placebo in the treatment of OCD, and social phobia, separation anxiety disorder or GAD in well controlled trials in paediatric patients. Reductions in symptoms of anxiety with fluvoxamine have been observed for up to 1 year in children and adolescents with OCD. However, there are currently no comparative trials of fluvoxamine with other pharmacological agents. In the absence of such trials, current consensus opinion recommends that when pharmacotherapy is indicated, fluvoxamine, like other SSRIs, can be used as first-line treatment for anxiety disorders, particularly OCD, in paediatric patients. However, direct comparisons are required to assess the relative efficacy and tolerability of pharmacological agents in order to make firm recommendations for the treatment of anxiety disorders in this patient group.

Adolescent↗

PubMed2005

Analgesia in PACU: nonsteroidal anti-inflammatory drugs.

Control and abolition of pain during and after surgical procedures is crucial point in the practice of anaesthesiology. In the last years the concept of multimodal analgesia (the use of different analgesic and techniques to relieve pain), has developed and non-steroidal anti-inflammatory drugs (NSAIDs) have a major role in it, because they have an opioid sparing effect. Moreover, they are very effective on somatic and breakthrough pain. NSAIDs can be divided functionally in four classes: salicylates, acetaminophen, non-specific inhibitors (i.e. ibuprofen, ketorolac, etc.) and cyclooxygenase2-inhibitors (coxibs). The target of action of these drugs is the different isozymes of the Prostaglandin G/H synthase, called Cyclooxygenases (COX). At least three different types of COX have been identified, which are probably organ specific. These isozymes play a crucial role in the developing of the inflammatory cascade, and in the genesis of various pain mediators released from tissue injury. Their most important side effects affect mainly gastrointestinal system, the kidney and the coagulation system. Less important are the effects on the liver and the immunologic system (asthma). The analgesic nephropathy and the coagulopathy must be taken into account in the surgical patient, for the possibility of increase perioperative morbidity. Very recently the newest class of coxibs, although they reduce g.i. bleeding and coagulopathy, have proved to increase the risk of cardiovascular accidents both in long term therapy than postoperatively in cardiac surgical patients. Many data are needed, but in patients at high risk of cardiac disease other NSAIDs should be considered.

Anti-Inflammatory Agents, Non-Steroidal↗