Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000729 (abdominal cramps)
 531 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The macrolides are a well established group of antibacterials frequently used in general practice. The most frequently used macrolides in paediatric patients are erythromycin, a naturally occurring compound, and clarithromycin and azithromycin, recently developed macrolides. Overall adverse effect rates of 7 to 26% for erythromycin, 14 to 26% for clarithromycin, and 6 to 27% for azithromycin have been described in children. Adverse gastrointestinal effects, including nausea, vomiting, diarrhoea and abdominal cramps, are the most common problems in children. Allergic reactions, hepatotoxicity, ototoxicity and adverse effects involving the central and peripheral nervous systems have also been observed in children. Stevens-Johnson, Schonlein-Henoch and Churg-Strauss syndromes have been rarely described in children. Treatment-related laboratory abnormalities have been recorded in 2 to 4% of erythromycin- and in 0 to 1% of both clarithromycin- and azithromycin-treated children. Elevation in liver function tests was the most common abnormality cited. Increased macrolide use in children in recent years has resulted in a growing potential for drug interactions between them and other pharmacologically active agents via the inhibition of cytochrome P450 (CYP) microsomal enzymes. Drug interactions with theophylline, cyclosporin, carbamazepine, terfenadine and warfarin limit erythromycin use. Clarithromycin is a weak inducer of CYP and exhibits fewer drug-drug interactions than erythromycin. However, its use with theophylline, carbamazepine and terfenadine is contraindicated. In contrast, no significant interactions have been reported with azithromycin to date. Macrolides have been proven to be well tolerated in the treatment of upper and lower respiratory tract infections, skin and soft tissue infections, and also in less frequent infections occurring in paediatric patients. In addition, clarithromycin and azithromycin have shown good tolerability profiles in immunocompromised paediatric patients. In conclusion, macrolides antibacterials have proven to be well tolerated in paediatric patients. Although the incidence of adverse effects is similar with the use of erythromycin and the newer macrolides, drug interactions occur significantly less when clarithromycin or azithromycin are administered.
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PMID:Comparative tolerability of erythromycin and newer macrolide antibacterials in paediatric patients. 993 75

I believe there are four essential elements in the management of patients with irritable bowel syndrome (IBS): to establish a good physician-patient relationship; to educate patients about their condition; to emphasize the excellent prognosis and benign nature of the illness; and to employ therapeutic interventions centering on dietary modifications, pharmacotherapy, and behavioral strategies tailored to the individual. Initially, I establish the diagnosis, exclude organic causes, educate patients about the disease, establish realistic expectations and consistent limits, and involve patients in disease management. I find it critical to determine why the patient is seeking assistance (eg, cancer phobia, disability, interpersonal distress, or exacerbation of symptoms). Most patients can be treated by their primary care physician. However, specialty consultations may be needed to reinforce management strategies, perform additional diagnostic tests, or institute specialized treatment. Psychological co-morbidities do not cause symptoms but do affect how patients respond to them and influence health care-seeking behavior. I find that these issues are best explored over a series of visits when the physician-patient relationship has been established. It can be helpful to have patients fill out a self-administered test to identify psychological co-morbidities. I often use these tests as a basis for extended inquiries into this area, resulting in the initiation of appropriate therapies. I encourage patients to keep a 2-week diary of food intake and gastrointestinal symptoms. In this way, patients become actively involved in management of their disease, and I may be able to obtain information from the diary that will be valuable in making treatment decisions. I do not believe that diagnostic studies for food intolerances are cost-effective or particularly helpful; however, exclusion diets may be beneficial. I introduce fiber supplements gradually and monitor them for tolerance and palatability. Synthetic fiber is often better-tolerated than natural fiber, but must be individualized. In my experience, excessive fiber supplementation often is counterproductive, as abdominal cramps and bloating may worsen. Antidiarrheal agents are very effective when used correctly, preferably in divided doses. I use them in patients in anticipation of diarrhea and especially in those who fear symptoms when engaged in activities outside the home. I encourage patients to make decisions as to when and how much to use. However, almost always, a morning dose before breakfast is used (loperamide, 2 to 6 mg) and, perhaps again later in the day when symptoms of diarrhea are prominent. I prefer antispasmodics to be used intermittently in response to periods of increased abdominal pain, cramps, and urgency. For patients with daily symptoms, especially after meals, agents such as dicyclomine before meals are useful. For patients with infrequent but severe episodes of unpredictable pain, sublingual hyoscyamine often produces rapid relief and instills confidence. In general, I recommend that oral antispasmodics be used for a limited period of time rather than indefinitely, and generally for periods of time when symptoms are prominent. For chronic visceral pain syndromes, I recommend small doses of tricyclic antidepressants. These agents are especially effective in diarrhea-predominant patients with disturbed sleep patterns but may be unacceptable to patients with constipation. I educate patients that side effects occur early and benefits may not be apparent for 3 to 4 weeks. I consider using SSRIs in low doses in patients with constipation-predominant IBS; cisapride, 10 to 20 mg three times per day, also may be beneficial. When taken with drugs that inhibit cytochrome P450, cisapride has been associated with serious cardiac arrhythmias caused by QT prolongation, including ventricular arrhythmias and torsades de pointes. These drugs include the azole fungicides; erythromycin, clarithromycin, and troleandomycin; some antidepressants; HIV protease inhibitors; and others. In patients with IBS with mild to moderate co-morbid depression, I have found that the use of SSRIs such as paroxetine, fluoxetine, or sertraline may be beneficial. It is important to tell patients that anxiety and disturbed sleep may occur during the first 10 days and benefits may not occur for 3 to 4 weeks. I prescribe a small amount of a short-acting benzodiazepine such as alprazolam, 0.5 mg two times per day, to control these symptoms. For generalized anxiety without depression, buspirone or clonazepam may be useful. I have found that patients who also have associated panic disorder may benefit from a benzodiazepine, tricyclic antidepressant, or an SSRI. However, these patients are best managed in conjunction with a psychiatrist or psychologist. I consider the use of alternative therapies in patients who fail to respond to conventional measures and who are receptive to alternative strategies. These include general relaxation techniques such as biofeedback and hypnosis therapies.
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PMID:Irritable Bowel Syndrome. 1109 67

The ingestion of seafood contaminated with the marine biotoxin okadaic acid (OA) can lead to diarrhetic shellfish poisoning with symptoms like nausea, vomiting and abdominal cramps. Both rat and the human hepatic cytochrome P450 monooxygenases (CYP) metabolize OA. However, liver cell toxicity of metabolized OA is mainly unclear. The aim of our study was to detect the cellular effects in HepG2 cells exposed to OA in the presence of recombinant CYP enzymes of both rat and human for the investigation of species differences. The results should be set in correlation with a CYP-specific metabolite pattern. Comparative metabolite profiles of OA after incubation in rat and human recombinant CYP enzymes were established by using LC-MS/MS technique. Results demonstrated that metabolism of OA to oxygenated metabolites correlates with detoxification which was mainly catalyzed by human CYP3A4 and CYP3A5. Detoxification by rat Cyp3a1 was lower compared to human CYP3A enzymes and activation of OA by Cyp3a2 was observed, coincident with minor overall conversion capacity of OA. By contrast human and rat CYP1A2 seem to activate OA into cytotoxic intermediates. In conclusion, different mechanisms of OA metabolism may occur in the liver. At low OA doses, the human liver is likely well protected against cytotoxic OA, but for high shellfish consumers a potential risk cannot be excluded.
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PMID:Differences in metabolism of the marine biotoxin okadaic acid by human and rat cytochrome P450 monooxygenases. 2637 42