Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sympathoadrenal activity was studied in 13 young piglets during hypoxia. The piglets were anaesthetized with chloralose/urethane, tracheostomized, paralyzed with gallamine and artificially ventilated. A femoral artery catheter was inserted and used for blood sampling. The piglets were challenged with 6 min of 6% CO2, 10 min of 12% O2 and 6 min of 6% O2 before and after theophylline (an adenosine receptor antagonist) treatment 20 mg/kg (n = 9) or saline (n = 4). Plasma samples were obtained before, during and after each hypercapnic or hypoxic period and analysed for their content of noradrenaline, adrenaline and neuropeptide Y. Hypercapnia with 6% CO2 and moderate hypoxia with 12% O2 did not lead to any significant increase of either noradrenaline (NA), adrenaline (A) or neuropeptide Y (NPY). However, severe hypoxia with 6% O2 increased the NA level from 30 to 66 nmol/l; the A level from 1 to 28 nmol/l and NPY from 140 to 213 pmol/l. After treatment with theophylline the baseline NA increased from 27 to 40 nmol/l, A rom 1.5 to 4.0 and NPY concentration from 65 to 171 pmol/l. Theophylline moderately enhanced the release of NPY, NA and A during the 12% O2 challenge. However, during the severe hypoxia (6%), the increase of NA (from 49 to 333 nmol/l), A (from 8 to 214 nmol/l) and NPY (from 184 to 385 pmol/l) showed considerably enhancement after the theophylline treatment. The results obtained before and after saline were similar showing that the duration of the experiments per se did not change the baseline levels or the effect of the challenges on NA, A or NPY levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y and catecholamine release in the piglet during hypoxia: enhancement by theophylline. 130 59

Theophylline is commonly believed to stimulate central respiratory centers. We studied the effect of oral theophylline therapy on ventilatory responses to hypercapnia and hypoxia during a double-blind placebo-controlled trial with a slow release oral theophylline preparation. We measured hypercapnic and hypoxic ventilatory responses using rebreathing techniques in 15 subjects (21 to 41 yr of age, with normal lung function) on three occasions: baseline, after 4 days of Drug 1, and after 4 days of Drug 2. For subjects receiving theophylline, the mean serum theophylline level was 11.3 + 1.3 (SE) micrograms/ml (range, 5.3 to 22.1). Unpleasant side effects were reported by 11 of the 15 subjects (nausea, jitteriness, and agitation) while receiving theophylline but not while receiving placebo. The mean hypercapnic ventilatory response with placebo was 4.3 +/- 0.9 L/min/mm Hg PACO2 and with theophylline it was 4.5 +/- 0.7 L/min/%SaO2 and with theophylline it was -2.7 +/- 0.4 L/min/%SaO2. Hypoxic responses for each subject were measured at similar PvCO2. There were no significant changes in ventilatory responses with theophylline. We conclude that theophylline use, at a dose sufficient to cause side effects, does not affect chemoreceptor responsiveness.
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PMID:Theophylline does not increase ventilatory responses to hypercapnia or hypoxia. 145 55

The present study reviews 62 children who where admitted to the department of pediatrics for acute bronchiolitis. We adopted the following therapeutic protocol: treatments were applied randomly and we administered a fast action theophylline solution (Theophylline Bruneau R) or a placebo solution every six hours by oral route or stomach probe at 10 mg/kg between 2 and 6 months, 12 mg/kg between 6 and 12 months and 16 mg/kg between 12 and 24 months. Evaluations of theophylline levels were systematically carried out (immunoenzymatic method) for every infant on day 1, day 3, and day 4 two hours after morning administration and the results studied to see if any changes were necessary. This treatment was well tolerated. Statistical analysis was performed before removal of blind. The homogeneity of the two groups was respected if we considered ages (placebo group: 7.1 months +/- 1.0, theophylline group: 5.6 months +/- 0.6), the initial seriousness as evidenced by hypoxemia (placebo group 61 +/- 2 Torr, theophylline group: 58 +/- 3 Torr) hypercapnia (placebo group: 37.8 +/- 1.0, theophylline group: 35.5 +/- 2) and chest retractions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of acute bronchiolitis in infants by oral suspension theophylline. Double-blind study in 62 children]. 389 10

The role of adenosine in the regional cerebral blood flow (rCBF) response to hypoxia was evaluated in young (6 month) and aged (26-28 month) F344 rats using theophylline, an adenosine antagonist. Regional CBF was measured with radioactive microspheres under control anesthetized conditions (70% N2O, 30% O2) and at two levels of hypoxia (CaO2 = 8.7-9.0 ml . 100ml-1 and 3.2-3.7 ml . 100ml-1). Without theophylline infusion, CBF increases were similar between young and aged rats during moderate hypoxia but were increased more in young during severe hypoxia. Intracerebrovascular theophylline infusion significantly attenuated the increase in CBF during both moderate and severe hypoxia and decreased the difference between young and aged rats. Theophylline infusion produced no significant effect on the increase in CBF produced by hypercapnia, indicating the specificity of the treatment for hypoxic induced CBF changes and adenosine release. Intracerebrovascular infusion of adenosine had no effect on CBF, presumably due to the presence of the blood brain barrier. The results suggest that adenosine plays a major role in CBF increases during both moderate and severe hypoxia and in the difference in response to hypoxia between young and aged rats.
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PMID:The role of adenosine in CBF increases during hypoxia in young vs aged rats. 669 16

This study investigated the effect of acute changes in blood gases and pH on theophylline kinetics. Groups of 6 conscious rabbits were exposed to air (control) or to a high CO2 and/or low O2 atmosphere for 570 minutes, or received 47 ml/kg of 0.3N HCl by gavage. Once blood gases or pH were stabilized, they received 2.5 mg/kg theophylline intravenously. Urine, blood samples, and cerebrospinal fluid were collected. Metabolic acidosis did not modify theophylline kinetics. Theophylline serum concentrations increased with hypercapnia (p less than 0.05), hypoxemia (p less than 0.01), and hypercapnia combined with hypoxemia (p less than 0.001), compared with those in control animals. These increases were related to a decrease in theophylline nonrenal clearance (Clnr). Thus, Clnr decreased from 1.52 +/- 0.05 ml/min/kg in control animals to 1.13 +/- 0.13 in hypercapnia (p less than 0.01), 1.09 +/- 0.09 in hypoxemia (p less than 0.001), and 1.02 +/- 0.02 in hypoxemia combined with hypercapnia (p less than 0.001). Theophylline protein binding was not affected by any of the experimental conditions. The ratio of central nervous system to serum theophylline concentration was increased by 16% (p less than 0.05) with hypercapnia combined with hypoxemia. It was concluded that both hypercapnia and/or hypoxemia decreased theophylline biotransformation. Such a decrease may be the cause of toxicity.
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PMID:Influence of hypercapnia and/or hypoxemia and metabolic acidosis on theophylline kinetics in the conscious rabbit. 672 Dec 73

Theophylline, a competitive adenosine antagonist, was used to evaluate the role of adenosine in cerebral hypoxic hyperemia. Cerebral venous outflow was measured by the Rapela-Green technique in mongrel dogs anesthetized with pentobarbital sodium and ventilated artificially. Theophylline was infused locally into the cerebral arterial system during moderate [cerebral venous O2 tension (PO2) 27-29 mmHg] or severe (cerebral venous PO2 = 10-15 mmHg) hypoxia; theophylline had no direct vascular effects at the concentration used. Cerebral hyperemia was completely reversed during moderate hypoxia, but only partially reversed during severe hypoxia when theophylline was infused during maintained hypoxia. Theophylline had no effect on cerebral; perfusion pressure, blood flow, or vascular resistance during normoxia. In another group, theophylline had no effect on the cerebral hyperemia induced by hypercapnia. In separate experiments, local cerebral arterial infusion of adenosine or AMP during normoxia had no effect on cerebral hemodynamics at any infusion rate tested (up to 100 micrograms/min). This study supports the hypothesis that adenosine is involved in the hyperemia associated with cerebral hypoxia. However, the degree of involvement may be dependent on the degree of hypoxia.
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PMID:Involvement of adenosine in cerebral hypoxic hyperemia in the dog. 727 Jul 1

Theophylline is a bronchodilator used extensively in the management of obstructive pulmonary disease. Factors implicated in altered theophylline clearance include smoking, age, concomitant drug intake, liver disease and left ventricular heart failure. However, evidence now suggests that theophylline clearance may be altered by changes in severity of the pulmonary obstruction, hypoxia and variation in arterial pH. The in vitro disposition of theophylline has been evaluated in isolated rat livers and mouse hepatocytes. In vivo studies have assessed the metabolism of theophylline under hypoxia in rats, rabbits and dogs. In isolated mouse hepatocytes and rat livers, low oxygen concentrations resulted in higher theophylline concentrations, a longer elimination half-life and a decrease in the production of the metabolite 1,3-dimethyl uric acid, suggesting impaired metabolism of theophylline. In rabbits, hypoxia, hypercapnia and respiratory acidosis decreased total body clearance and increased plasma theophylline concentrations. On the other hand, experiments involving dogs showed no significant changes in theophylline concentrations or pharmacokinetic parameters with hypoxia. At present, animal studies remain inconclusive. This can be attributed to the use of different animal models and variations in study methodology, including the extent and duration of hypoxia and acidaemia, concurrent acid-base disorders such as hypercapnia, as well as the severity of pulmonary obstruction. Human studies assessing alterations in theophylline disposition secondary to the hypoxia present in pulmonary disease are few and include mostly case reports and observational studies. There is evidence suggesting decreased theophylline clearance and protein binding during acute illness and some consensus can be achieved using case reports and controlled studies. There is additional evidence that drug clearance decreases with age and that elderly patients may have a decreased theophylline clearance at baseline. However, the most obvious markers appear to be the severity of pulmonary disease and the rate of change in the patient's condition. Caution should be exercised when administering theophylline to elderly patients with chronic obstructive pulmonary disease presenting with acute exacerbations of a concomitant respiratory illness, as these patients appear to be most likely to exhibit altered theophylline metabolism. Therefore, they would be at increased risk for toxicity should conventional dosages be used during an acute respiratory event.
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PMID:Hypoxia, arterial pH and theophylline disposition. 826 13

Asthma is a common and debilitating problem in children. Its many costs to society include morbidity, hospitalization and treatment expenses, and a rising mortality rate. This paper examines recent trends in therapy for status asthmaticus. Oxygen, inhaled beta-adrenergic agonists, and corticosteroids remain the cornerstones of therapy for the child with a severe exacerbation of asthma. Ipratropium bromide provides additional bronchodilatation in the patient who does not respond to standard therapy. Theophylline may have a role in chronic outpatient management of asthma, but the data supporting the addition of this medication in acute therapy for status asthmaticus are inconclusive. Antibiotics are only indicated in children with asthma complicated by infection, such as sinusitis or pneumonia. Magnesium sulfate and heliox may have a role in helping the asthmatic child who is critically ill and for whom other interventions have failed. Mechanical ventilation has many complications. The concept of permissive hypercapnia may be important in limiting barotrauma. Prevention of exacerbations of asthma include limiting environmental exposure to allergens and tobacco, using corticosteroids, and reinforcing compliance with therapy.
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PMID:Update on the management of status asthmaticus. 881 99