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Query: KEGG:D01453 (caffeine)
 21,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of caffeine and other methylxanthines in prematurity, intrauterine growth retardation, and the respiratory distress syndrome is currently under investigation. Their pharmacokinetics are discussed together with their newly discovered beneficial role as possible inhibitors of premature labor and accelerators of fetal lung maturation.
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PMID:Effects of methylxanthines on the fetus. 22 87

Caffeine is commonly used in the treatment of apnea of prematurity. The skin of preterm infants varies considerably in its level of maturity. To understand skin absorption in low birthweight infants (less than 1500 gm) with gestational age between 26 and 34 weeks, a group of 56 preterm babies was studied after percutaneous application of 7.5 mg twice daily of caffeine for babies with birthweight less than 1000 gm and 10 mg twice daily for babies with birthweight more than 1000 gm. The reported technique is a useful alternative method of drug administration in premature babies. This study indicates an inverse relationship between gestational age and skin absorption contributing to a better understanding of skin barrier function in the newborn.
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PMID:Developmental aspects of percutaneous caffeine absorption in premature infants. 141 50

In contrast to its effect on airway smooth muscle in the adult, in vitro studies have shown that caffeine significantly increases active tension in airway smooth muscle in the neonatal lamb. To determine if caffeine has a physiological effect on airway function during early development, we studied the effect of caffeine on acetylcholine-induced bronchoconstriction in two groups of neonatal lambs. The animals were anesthetized, paralyzed, and maintained normoxic and normocapnic with mechanical ventilation. Pulmonary mechanics were evaluated as indices of airway tone, and functional residual capacity was used as an index of lung volume; heart rate and mean arterial pressure were used to assess cardiovascular status. Acetylcholine-induced bronchoconstriction was evaluated as percentage changes of airway conductance and lung compliance from baseline, before and 1 hour after administration of normal saline or caffeine, and it was further analyzed with respect to the dose that produced a 20% change in those values (PD20). There were no significant alterations in baseline lung mechanics, lung volume, or mean arterial pressure following saline or caffeine infusion. However, caffeine produced a left shift in the acetylcholine dose-response curve for conductance and compliance and a significant decrease (-52%; P less than 0.001) in PD20 for conductance. There were no significant alterations in any parameter following saline administration. Since caffeine is used commonly for the treatment of apnea of prematurity, it is noteworthy that caffeine increases airway reactivity at clinically relevant doses. These findings raise important issues regarding the use of caffeine for the treatment of apnea of prematurity.
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PMID:Caffeine potentiates airway responsiveness in the neonatal lamb. 157 70

It is well known that the strength of postextrasystolic potentiation (PESP) is dependent on the prematurity of the ectopic beat, though the fundamental mechanism of the potentiation is still obscure. In this study, the effect of a resting interval on the strength of PESP was investigated in isolated papillary muscles of guinea pigs in the presence or absence of caffeine, which inhibits the functions of sarcoplasmic reticulum (SR). PESP of a fixed coupling interval increased and then decreased as the resting interval was prolonged. The maximum of PESP was obtained at a resting interval of 3 to 4 sec. The dependency of PESP on a coupling interval was decreased considerably by 5 x 10(-4) M caffeine and removed completely by 10(-2) M caffeine. Although 5 x 10(-4) M caffeine decreased the degree of contraction of postextrasystole, the maximum contraction of postextrasystole was still obtained at a resting interval of 3 to 4 sec. After the application of 10(-2) M caffeine, the postextrasystolic contraction gradually declined as the resting interval was prolonged. We conclude that SR Ca release contributes largely to a mechanism of PESP and increases in contribution as the coupling interval of an extrastimulation shortens, and that the optimal resting interval is determined by a balance between the activity of SR function and the activity of the sarcolemmal Ca extrusion mechanism.
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PMID:Suppressing effects of caffeine on postextrasystolic potentiation in papillary muscles of guinea pigs. 169 71

Studies were done to determine whether the apparent changes in behavioral sensitivity to adenosine receptor ligands that occur with age and with neonatal caffeine exposure were due to a change in sensitivity of the receptor for the ligand or to a more fundamental change in the receptor. Using an animal model that mimics the brain developmental period and level of caffeine exposure in human premature neonates treated with caffeine for apnea of prematurity, behavioral and neurochemical investigations were undertaken. The locomotor responses to acute challenge with caffeine (15, 30 and 60 mg/kg) and with D-phenylisopropyladenosine (D-PIA) (0.038 and 0.38 mg/kg), an adenosine receptor agonist, were measured in control and neonatally caffeine-exposed rats at 12, 15, 18, and 28 days of age. The dissociation constants (Kd) and maximal binding densities (Bmax) for agonist binding at the adenosine A1 receptor site were determined over a similar time period. Caffeine displacement of an adenosine A1 agonist was also measured to examine in vitro sensitivity to caffeine as a function of age and neonatal caffeine exposure. Our studies demonstrated that the differential responses to adenosine receptor ligands seen as a function of both age and neonatal caffeine exposure could not be overcome by merely increasing the doses of ligand administered. In addition, the results of the binding studies indicated that changes in the adenosine receptor are occurring as a function of age in different regions of the brain of control animals and that this development is influenced by neonatal caffeine exposure.
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PMID:Neonatal caffeine exposure alters developmental sensitivity to adenosine receptor ligands. 181 68

Caffeine is a methylxanthine, commonly used in the premature neonate to treat apnea of prematurity. It is efficacious and appears to have few short-term side effects. An animal model, designed to mimic the developmental period in brain and level and duration of exposure in humans, was used to investigate possible long-term effects of early developmental exposure to caffeine on the ontogeny of the adenosine receptor to which caffeine binds. Specific binding at the adenosine A1 receptor, in five distinct regions of the brain was determined in rats, 14-90 days old, as a function of early postnatal exposure to caffeine, over days 2-6. In cortex, cerebellum and hippocampus but not in the brain stem or hypothalamus, there was an increase in specific binding, following neonatal exposure to caffeine, compared to specific binding in control animals. Kinetic analysis of binding to the A1 site in cortical tissue suggests that this increase was due to an increased maximum binding density (Bmax); binding affinity (Kd) did not change. Thus, limited exposure to caffeine, in the early neonatal period, may result in up-regulation of the adenosine A1 receptor that persists to young adulthood in the rat.
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PMID:Neonatal exposure to therapeutic caffeine alters the ontogeny of adenosine A1 receptors in brain of rats. 186 95

An animal model was developed to approximate the magnitude and brain developmental period of caffeine exposure experienced by the human infant receiving caffeine for apnea of prematurity. Serum levels of caffeine of 5-15 mg/l over the 24-hour period were achieved by administering to rat pups a loading dose of 20 mg/kg p.o. on day 2, followed by 15 mg/kg p.o. on days 3-6 of life. Locomotor activity, both spontaneous and following an acute challenge with D-phenylisopropyl adenosine (an adenosine receptor agonist, 10 mumol/kg i.p.) or caffeine (an adenosine receptor antagonist, 100 mumol/kg i.p.), was measured in 12-to 28-day-old native rat pups or pups neonatally exposed to caffeine. The stimulatory effect of acute caffeine on locomotor activity was developmentally delayed in neonatally exposed pups. It is postulated that early exposure to caffeine in some way altered the development of the central adenosine receptor control over locomotor activity.
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PMID:Neonatal caffeine exposure alters adenosine receptor control of locomotor activity in the developing rat. 207 77

In a double blind study, two comparable groups (each n = 10) of premature infants less than 34 weeks of gestational age, with idiopathic apnea were given an IV treatment of either theophylline or caffeine. The loading doses were respectively 6 and 10 mg/kg and the maintenance doses were 2 and 1.25 mg/kg every 12 hours. In both groups, apneas greater than or equal to 15 s. with or without bradycardia were similarly reduced (p less than 0.01). Both drugs increased significantly the respiratory rate. Compared to caffeine, theophylline induced a significant acceleration of heart rates, an increase in urinary sodium excretion, more frequent gastrointestinal intolerance and behavioral changes. Plasma concentrations of theophylline were less stable than those of caffeine. These data suggest that a single daily dose of caffeine should be preferentially used in the treatment of idiopathic apneas of prematurity.
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PMID:[The choice between theophylline and caffeine in the treatment of apnea in premature infants]. 220 8

The incidence and proposed mechanisms of apnea of infancy and apnea of prematurity are briefly reviewed, and the use of methylxanthines in managing these conditions is discussed. Apnea may result from incomplete neurological development of the infant. A sleep-related defect in respiratory control mechanisms has been proposed. Apnea may be secondary to physiologic abnormalities that cause airway obstruction or to cardiac disease or arrhythmia, seizure disorders, infection, or other disorders. Therapy often includes supportive management. The primary pharmacologic agents used to treat apnea of prematurity are caffeine and theophylline. The metabolism of these drugs differs greatly between newborns and adults and changes rapidly in the first nine months of life; in infants up to 4 1/2 months of age, the half-life of these compounds is prolonged. While only theophylline is approved in the United States for management of apnea, caffeine has several potential advantages. However, no suitable caffeine product is available. The accepted pharmacologic treatment for apnea of prematurity is the use of the methylxanthines theophylline and caffeine. Theophylline has also been used in treating apnea of infancy, although there are fewer data documenting its efficacy for this indication.
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PMID:Management of apnea in infants. 267 Mar 99

Administering caffeine citrate is a safe, noninvasive way to treat premature infants with persistent apnea. This drug decreases the frequency of apneic episodes, thus reducing the need for mechanical ventilation. It is given once a day, either orally or intravenously. Ideally, caffeine citrate can treat apnea of prematurity and prevent insults to the premature infant's neurological status.
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PMID:Caffeine citrate in the NICU. 270 53


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