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)

The usefulness of xanthine bronchodilators in the treatment of asthma is often limited by the side effects of nausea and vomiting. We investigated the mechanism of emesis induced by xanthines, by examining the roles of phosphodiesterase (PDE) inhibition and adenosine antagonism. Theophylline, enprofylline, 8-phenyltheophylline and isobutylmethylxanthine (IBMX), as well as vehicle, were given to ferrets at doses ranging from 0.1 to 150 mg/kg i.p. The potencies of these compounds in producing emetic responses were ranked IBMX greater than enprofylline greater than theophylline greater than 8-phenyltheophylline. These results correlate well with the relative potencies of the compounds as nonselective PDE inhibitors but do not correlate with their relative potencies as adenosine A1 or A2 receptor antagonists. The emetic responses also correlate well with the previously reported potencies of these xanthines as bronchodilators in guinea pigs. We conclude that the emetic side effect of xanthine bronchodilators results from the inhibition of one or more forms of PDE rather than from adenosine antagonism.
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PMID:Mechanism for the emetic side effect of xanthine bronchodilators. 168 99

Theophylline has been demonstrated to be a useful agent in the therapy of chronic asthma. Its use must be tempered with knowledge of its adverse effects and that these effects are related primarily to serum concentration. Accordingly, it is mandatory to monitor serum theophylline concentrations on a regular basis with any patient receiving maintenance therapy with theophylline. It is also necessary to recognise the potential side effects of theophylline therapy, and when such a patient displays symptoms of vomiting, headache or seizures, serum theophylline concentration must be checked even if a recent concentration was within the therapeutic range. The means for monitoring theophylline concentrations are now available even to the average physician who does not have immediate access to a laboratory that can provide timely serum theophylline determinations.
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PMID:Therapeutic monitoring of theophylline. Rationale and current status. 268 38

In 27 cases of acute severe asthma, a loading dose of 5 mg/kg of aminophylline (omitted if already receiving oral theophylline) followed by a continuous infusion of 1 mg/kg per hour gave satisfactory theophylline levels at 4 h and 24 h. Theophylline clearance rates varied widely, vomiting was common, but unrelated to blood theophylline levels.
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PMID:Aminophylline dosage in acute severe asthma. 274 23

Theophylline, with its narrow therapeutic margin, is a common cause of iatrogenic and deliberate overdose. Most cases of self-poisoning are with sustained release preparations, with peak concentrations occurring up to 12 or more hours after overdose. Toxic symptoms are often seen at concentrations above 15 mg/L. Theophylline is metabolised within the cytochrome P-450 system, with an average total body clearance of 50 to 60 ml/min. Clearance is, however, affected by many factors such as other drugs or disease, and in overdose zero order kinetics may result in prolonged half-lives. Toxicity is characterised by agitation, tremor, nausea, vomiting, abdominal pains, seizures, and tachyarrhythmias. Hypokalaemia and metabolic acidosis are more profound in acute toxicity, and hypercalcaemia is usually present. Seizures occur at lower concentrations after chronic over-medication than after acute overdose. Gastric lavage should be performed in all patients presenting early, and an oral multiple dose charcoal regimen started with 50 to 100g charcoal, repeating with 50g doses and checking theophylline concentrations at 2- to 4-hour intervals. Multiple dose charcoal can be expected to double the clearance of theophylline, being as effective as a haemodialysis. Of the invasive techniques available, charcoal haemoperfusion is the most effective, increasing clearance 4- to 6-fold. Supportive care is particularly important. The aggressive supplementation of potassium, treatment of emesis with droperidol and ranitidine, and treatment of tachyarrhythmias and hypotension (possibly with propranolol), together with oral multiple dose charcoal may obviate the need for haemoperfusion. Seizures suggest increased morbidity and mortality. Charcoal haemoperfusion should be considered if plasma concentrations are greater than 100 mg/L in an acute intoxication or greater than 60 mg/L in a chronic intoxication. The decision to haemoperfuse should not be based on plasma concentrations alone, but an overall evaluation of the patient's laboratory and clinical status.
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PMID:Role of extracorporeal drug removal in acute theophylline poisoning. A review. 330 69

This study was conducted to determine whether intravenous theophylline, added to inhaled albuterol and intravenous methylprednisolone, provides a clinically significant benefit in the treatment of pediatric status asthmaticus. Patients aged 2 to 10 years were randomized to receive either intravenous theophylline or placebo. All patients received aerosolized albuterol and intravenous methylprednisolone. There was no difference between groups in the improvement of a clinical asthma score over time, in oxygen requirement, or in the number of albuterol treatments required. Theophylline group patients experienced more nausea, emesis, and insomnia. We conclude that there is no benefit in adding theophylline to treatment with methylprednisolone and albuterol for pediatric status asthmaticus. Furthermore, there are significantly more adverse effects associated with the use of theophylline.
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PMID:Intravenous theophylline in pediatric status asthmaticus. A prospective, randomized, double-blind, placebo-controlled trial. 758 20

Theophylline has been a mainstay of asthma therapy despite its narrow therapeutic index, which makes toxicity a common problem. To study toxicity in children, we reviewed hospital laboratory records (1980 to 1988) and identified cases (n = 163) with theophylline concentrations of > 133 mumol/L (24 micrograms/ml). We reviewed these cases for symptoms of theophylline intoxication; we were interested in associating symptoms with serum drug concentrations and in understanding how intoxication occurred. The median patient age was 3.0 years; 40/163 were younger than one year. Males were 90/163 patients (55%). Patients were classified by pattern of ingestion: 20 patients had acute ingestions; 17 patients had an acute ingestion while on chronic medication; and 126 patients became toxic on chronic therapy. Symptoms were absent in 44/150 patients (29%) with theophylline concentrations of 139 to 278 mumol/L (25-50 micrograms/ml); concentrations of > 278 mumol/L (50 micrograms/ml) were always associated with symptoms. The most common clinical symptoms were tachycardia (47%) and vomiting (52%); both occurred more frequently with higher theophylline concentrations (P < 0.002 and P < 0.01). Nine patients had seizures, including five who were previously neurologically normal. Seizures developed with a theophylline concentration of < 278 mumol/L (50 micrograms/ml) in four of these five patients. There was no association between seizures and patient age or between seizures and a particular pattern of theophylline use. In 105/126 cases of intoxication associated with chronic use, the cause of the intoxication could not be determined. Appropriate management of theophylline toxicity can occur only if toxicity is recognized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Theophylline toxicity in children: a retrospective review. 834 82

Theophylline has been used for over a century in the treatment of asthma and while it is used principally as a bronchodilator, a number of recent studies have demonstrated potential anti-inflammatory and immunomodulatory activity. Indeed, regular treatment with low-dose theophylline, affords significant clinical benefit at the expense of unwanted side-effects associated with this drug, including headache and vomiting. The mechanism of action of theophylline is unclear, although a significant body of evidence points to an involvement of phosphodiesterase enzyme inhibition. Phosphodiesterases are a diverse group of enzymes that belong to at least seven families and of particular interest is the role of phosphodiesterase 4 isoenzyme as it is distributed in a number of inflammatory and immune cells and whose inhibition results in the downregulation of inflammatory and immune cell function. The discovery of pharmacological drugs selective for this isoenzyme has been viewed with interest in light of the positive results from preclinical and early clinical studies. Whether orally active safe phosphodiesterase 4 isoenzyme inhibitors will be useful in the treatment of asthma remains to be established.
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PMID:The role of theophylline and phosphodiesterase4 isoenzyme inhibitors as anti-inflammatory drugs. 975 83

The purpose of this study was to evaluate the relationship between acute and subacute toxicity and blood levels of theophylline in dogs. Theophylline was administered intravenously into dogs once (at doses of 50, 100 and 150 mg/kg) or for 4 weeks (at doses of 20, 35 and 70 mg/kg/day). In the single dose toxicity study, by increasing the dose of theophylline, plasma concentration increased and the severity of toxic symptoms were intensified. After a single dosing of theophylline, accentuated heart rate and vomiting were observed at a concentration of more than 67 micrograms/ml, and excitement, spasm and hyperpnea were observed at more than 130 micrograms/ml. Animals died after tonic convulsion at 180 micrograms/ml. In the repeated dose toxicity study, the plasma concentration of theophylline increased dependent on dosage, and was not affected by repeated dosing. Even under these conditions, the toxic symptoms were quite similar to those of the single dose, except for an additional decrease in movement, body weight reduction and myocardial lesion. These present results suggest that the severity of theophylline toxicity is dependent on its plasma concentrations rather than accumulated dosages. The blood concentration of theophylline-treated patients should be maintained within the therapeutic range in order to diminish risk.
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PMID:Acute and subacute toxicities of theophylline are directly reflected by its plasma concentration in dogs. 1089 1

Intravenous aminophylline is effective in children with acute asthma and was the bronchodilator of choice for many years. However, with the advent of inhaled b agonists and anticholinergic agents an alternative, less invasive, therapeutic strategy is currently available. If children with acute asthma fail to respond to inhaled therapy clinicians may consider aminophylline a controversial treatment. The published evidence on whether aminophylline produces further beneficial effect in children already receiving inhaled therapy for acute asthma is reviewed in this paper. The published randomised controlled trials comparing aminophylline with placebo are of good methodological quality, although the numbers of children in many of the studies are small. Trial outcomes included lung function (FEV1 and PEF) and clinical scoring of asthma severity. Aminophylline improved percentage predicted FEV1 by 6 hours, and this effect was maintained for 24 hours. Improvements were also seen in clinical asthma severity scores at 6 hours. Despite improvements in lung function and asthma severity, there was no reduction in hospital stay or the number of nebulisers required. The main side effect of aminophylline therapy was an increased incidence of vomiting. In conclusion, the addition of intravenous aminophylline should be considered early in the treatment of children hospitalised with acute severe asthma with suboptimal response to the initial inhaled bronchodilator therapy. Further research should be carried out to examine whether intravenous aminophylline may have a beneficial effect in other settings such as intensive care to determine if it may reduce intubation and ventilation rates.
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PMID:The current role of intravenous aminophylline in acute paediatric asthma. 1460 79

A retrospective study was undertaken to assess the association between esophageal pH monitoring variables and signs such as regurgitation, vomiting, apnea, bradycardia, and cyanotic episodes attributable to gastroesophageal reflux (GER) in neonates. One hundred thirty-four infants with one or more of the above-described signs underwent 24-hour distal esophageal pH monitoring in the neonatal intensive care unit, and were divided into 2 groups by gestational age. Group 1 (preterm infant group) consisted of infants aged 25 to 36 weeks of gestation ( n = 45) and group 2 (term infant group) consisted of infants aged 37 to 42 weeks gestation ( n = 89). Esophageal pH monitoring variables were compared by gestational age group and within preterm infants by theophylline treatment and, separately, by nasogastric tube using the Mann-Whitney U test. Comparisons of nominal data were made using the chi square test. Logistic regression analysis was used to assess the net effect of each independent variable on the risk of developing GER. The prevalence of GER was not influenced by gestational age. The prevalence of gastrointestinal signs did not differ between groups. Cardiorespiratory signs attributed to GER were more frequent in preterm infants than in term infants. The number of episodes with pH < 4 in 24 hours was greater in the term compared with the preterm infant groups. Logistic regression analysis failed to detect an association between acid GER and gestational age, apnea, bradycardia, cyanotic episodes, vomiting, or regurgitation. Theophylline treatment and the presence of a nasogastric tube did not significantly affect the esophageal pH monitoring variables in preterm infants. Preterm infants have a smaller number of reflux episodes compared with term infants. In addition, treatment with theophylline for apnea of prematurity and the presence of a nasogastric tube in preterm infants did not significantly affect pH-monitoring variables in preterm infants.
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PMID:Esophageal pH study and symptomatology of gastroesophageal reflux in newborn infants. 1501 72


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