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Biomedical subjects

J V Aranda

Publications and source records attributed to J V Aranda.

At least 73 records · Page 4Linked to original sources
PubMed1986

Interaction between chloramphenicol and acetaminophen.

Acetaminophen has been reported either to prolong or not to affect the clearance of chloramphenicol. To confirm one of these findings we studied the clearance of chloramphenicol and its metabolites using high pressure liquid chromatography in five patients (ages 2.5 to 5 years) before and during oral treatment with acetaminophen (50 mg/kg/day). Significant differences were observed in mean (SD) peak serum chloramphenicol concentration (-9.7 (3.2) mg/l), mean (SD) apparent volume of distribution (+225 (162) ml/kg), mean (SD) chloramphenicol half life (-1.9 (1.1) hours), mean (SD) chloramphenicol clearance (+236 (94) ml/kg/h), mean (SD) area under the curve (-83.5 (33.0) mg/l/h), and mean (SD) elimination constant (+0.34 (0.13) h-1) between samples obtained before and during treatment with acetaminophen. Acetaminophen, when given orally for several days, increased the clearance of chloramphenicol, perhaps by increased glucuronidation. This report re-emphasises the need for therapeutic drug monitoring whenever these two drugs are used together.

Acetaminophen↗
PubMed1986

Apnoea and seizures.

We report two infants with near miss sudden infant death syndrome events exhibiting seizure disorders after caffeine treatment, suggesting there is an infant subgroup diagnosed as near miss sudden infant death syndrome who have apnoea possibly with seizures whose seizure threshold may be lowered by central nervous system stimulants like caffeine.

Apnea↗
PubMed1986

Dose effect of caffeine on control of breathing and respiratory response to CO2 in cats.

The dose effect of caffeine (10-70 mg/kg iv) on pulmonary ventilation (VE), mean inspiratory flow (VT/TI), and tracheal pressure generated 0.3 and 0.5 s (P0.3 and P0.5, respectively) after the onset of inspiration against airway occluded at end expiration was studied in cats anesthetized with pentobarbital sodium (35 mg/kg ip) breathing various gas mixtures. With air and 50% O2 (balance N2), increasing doses of caffeine caused a progressive increase in VE that was associated with a reduction in end-tidal PCO2. When the latter was maintained at control (precaffeine) level by inhalation of CO2, the increase in VE was, at all caffeine levels, about three times that under nonisocapnic conditions. Both under isocapnic and nonisocapnic conditions the greatest incremental changes of VE were observed after administration of the first 10-mg/kg aliquot of caffeine, i.e., the current acceptable clinical dose. In all instances, the changes in VE were proportionally the same as the corresponding changes in VT/TI, P0.3, and P0.5, suggesting that caffeine did not appreciably alter either the shape of the inspiratory driving pressure waveform or the impedance of the respiratory system but simply acted by increasing the amplitude of the neuromuscular inspiratory output. An additive interaction between caffeine and end-tidal PCO2 was observed in the VE, VT/TI, and P0.3 responses at levels of CO2 at or below the eucapnic range.

Animals↗
PubMed1986

Abolition of ventilatory response to caffeine in chemodenervated lambs.

In this study we have evaluated the role of the peripheral chemoreceptors in the ventilatory response to caffeine at a dose currently used in human infants for treatment of central apneas (10 mg/kg). Twelve lambs were studied; six had carotid body denervation (CBD) and six had a sham denervation (intact). The denervation was done the 2nd wk of life, and the study of the response to caffeine infusion was carried out at a mean age of 82 days. The awake and nonsedated animals received 10 mg/kg of caffeine, and caffeine blood levels were, respectively, 8.8 and 9.0 mg/l in the intact and in the CBD lambs. The intact lambs responded to caffeine by a significant immediate increase in minute ventilation (VE) of 46% from 274 to 400 ml X min-1 X kg-1 (P less than 0.001), 1 min after caffeine infusion. This response rapidly faded, but VE was still increased at 2 h, 314 ml X min-1 X kg-1. The increase in ventilation was brought about by a change in mean inspiratory flow (VT/TI), which increased from 9.9 to 14.0 ml X s-1 X kg-1 within 1 min (P less than 0.01); VT/TI was still increased at 11.2 ml X s-1 X kg-1 2 h later. In contrast, for the CBD lambs there was no response to caffeine infusion as measured by VE or VT/TI. We conclude that bolus caffeine infusion produces a rapid response in VE followed by a fall in VE that remained above base line until at least 2 h postinfusion, and the intact chemoreceptor function appears as an essential mediator for these increases in ventilation, since the peripheral chemodenervation has completely abolished the VE response to this particular dose of caffeine.

Animals↗
PubMed1986

Indomethacin metabolism in liver microsomes during postnatal development in the rat.

Indomethacin is now widely used during the neonatal period, but few data exist concerning its metabolism during this period. Thus, we studied the maturational changes in the metabolism of indomethacin into desmethylindomethacin by isolated liver microsomes from 1- to 60-day-old rats. From 8 days of age on, there was a progressive increase in enzymatic activity which was inversely correlated with the change in Michaelis-Menten constant. However, the maximal velocity was not significantly affected by the age. These findings suggest that the deficient metabolism of indomethacin in the newborn rat is due to decreased affinity between enzyme and substrate, or presence of competitive inhibitors. To determine the substrate specificity of the monooxygenase-catalyzing inducers, sodium phenobarbital and beta-naphthoflavone given during 3 days in neonatal rats were also studied. Although beta-naphthoflavone did not exhibit any significant effect, phenobarbital significantly increased the activity and maximal velocity of indomethacin O-demethylation.

Aging↗
PubMed1986

Effect of phenobarbital on cerebral blood flow in the newborn piglet under stress.

Heart rate, cardiac output, mean arterial blood pressure (MABP), and cerebral blood flow (CBF) were measured in 12 newborn piglets (6 controls and 6 pretreated with 20 mg/kg phenobarbital), under two different stresses: pain stimulation and intravenous injection of 2.5 mg/kg phenylephrine. Phenobarbital prevented pain-induced tachycardia (p less than 0.05 versus controls) but failed to prevent hemodynamic changes induced by phenylephrine. CBF remained relatively constant throughout the study. A better correlation between cerebral vascular resistance and MABP was noted in the phenobarbital group (r = 0.58, p less than 0.01) than in the controls (r = 0.15, p = NS), suggesting that phenobarbital potentiates the vasoconstrictor effect of catecholamines.

Animals↗
PubMed1984

Effects of ethacrynic acid in the newborn infant.

The effects of ethacrynic acid on electrolyte and water excretion were examined in 10 neonates with fluid overload states. Ethacrynic acid (1 mg/kg IV) produced a 10-fold increase in FENa+ and FECl - and a sixfold increase in urine volume and osmolar clearance. These effects peaked within 1 hour of ethacrynic acid administration, and progressively decreased to the baseline value by 5 hours after drug administration. The mean excretion of potassium increased by 280% in 1 hour, and returned to baseline value after 5 hours. The mean Ca++ excretion increased fourfold after 1 hour, and the effect lasted for 4 hours. Two infants developed mild hyponatremia. Our data emphasize the prolonged diuretic and saluretic effect of ethacrynic acid in neonates.

Chlorides↗
PubMed1984

The pharmacokinetics and metabolism of cimetidine in neonates.

Cimetidine pharmacokinetics and metabolism were studied in 2 full-term and 1 premature neonates. All infants demonstrated the capacity to eliminate cimetidine via both metabolic and renal routes. The half-life of cimetidine ranged from 3.4 to 2.1 h, and decreased as total body clearance increased. These alterations in pharmacokinetics were felt to represent developmental and maturational differences, primarily in renal function. In contrast to the 60% routinely seen in adults, approximately 90% of the administered dose was recovered in the urine of the full-term infants as cimetidine and its known metabolites. Cimetidine sulfoxide and hydroxymethyl cimetidine were detected in the serum and urine of 2 patients, and the elimination half-life of these metabolites was two- to threefold longer than values seen for cimetidine. During multiple dosing of cimetidine, significant accumulation of cimetidine metabolites may be expected. The reported dose of 15-20 mg/kg/day is adequate in full-term neonates, however, it appears that premature infants and those with renal dysfunction may require lower dosing rates.

Biotransformation↗
PubMed1983

Effect of caffeine on control of breathing in infantile apnea.

Abnormalities in control of breathing have been associated with near-miss sudden infant death syndrome. Because caffeine is a respiratory stimulant, its effect on breathing pattern was evaluated in 12 infants with infantile apnea. Caffeine induced a significant increase in ventilation, tidal volume, and mean inspiratory flow. In contrast, no changes were noted in inspiratory time, expiratory time, or total cycle duration. These effects were observed with plasma concentrations of caffeine ranging from 8 to 20 mg/L. Caffeine increases ventilation mainly by increasing central inspiratory drive, and not be effective timing (T1/TTOT). This drug may be of value in near-miss SIDS.

Apnea↗
PubMed1983

Changing pattern of drug utilization in a neonatal intensive care unit.

Drug exposures in neonates admitted to a neonatal intensive care unit in 1974 and in 1977 were compared. A significant increase in drug exposure (3.4 drugs per baby in 1974 versus 6.19 drugs in 1977) and in the total number of drugs used (71 versus 102 different drugs) were noted. The proportion of infants receiving no drugs were similar (23%). Infants given penicillin and kanamycin decreased by about 50% with a reciprocal increase observed with ampicillin and gentamicin. Except for a few drugs (chloramphenicol, methicillin, Infantol), all drugs were used in a greater number of babies in 1977. Data indicate increase in drugs used and a change in the pattern of drug utilization over a period of three years.

Canada↗
PubMed1983

Interaction of caffeine and continuous distending airway pressure in neonatal apnea.

The interactive effect of caffeine and continuous distending airway pressure was evaluated in two premature neonates with apnea. The application of a continuous negative pressure around the chest wall decreased minute ventilation in both infants and blunted the stimulatory effect of caffeine. This potential interaction should be considered if the desired effects of caffeine or distending airway pressure on apnea control are not achieved when they are used concurrently.

Apnea↗
PubMed1983

Effect of caffeine on skeletal muscle function before and after fatigue.

We studied the effect of caffeine on voluntary and electrically stimulated contractions of the adductor pollicis muscle in five adult volunteers. Caffeine (500 mg) was administered orally in a double-blind fashion. Electrical stimulation of the ulnar nerve was performed at 10, 20, 30, 50, and 100 Hz before and after a sustained voluntary contraction held at 50% of the maximal voluntary contraction (MVC). A brief tetanus at 30 Hz was also performed to calculate relaxation rate in the fresh muscle. Contractile properties, relaxation rate, and endurance were then assessed after caffeine and placebo, as well as the response of the fatigued muscle to different frequencies of stimulation. There was no difference in the maximal tension obtained with electrical stimulation (T100) or in the MVC between placebo and caffeine. The tensions developed with electrical stimulation at lower frequencies increased significantly with caffeine ingestion, shifting the frequency-force curve to the left, both before and after fatigue. Mean plasma caffeine concentration associated with these responses was 12.2 +/- 4.9 mg/l. We conclude that caffeine has a direct effect on skeletal muscle contractile properties both before and after fatigue as demonstrated by electrical stimulation.

Adult↗
PubMed1983

Effect of caffeine on thyroid and pituitary function in newborn rats.

The possibility that caffeine, a central nervous system stimulant used in neonatal apnea, may produce acute or chronic changes in growth hormone (GH), thyroxine (T4) and thyrotropin (TSH) was studied in the newborn rat. Five-day-old rats were separated into three groups: control (0) group receiving saline, Group I (low dose caffeine) receiving 5 mg/kg and Group II (high dose caffeine) receiving 50 mg/kg. Acute effects were studied at 2, 4, and 24 h after injection. Chronic effects were studied 24 h after the last of 10 daily injections. GH, T4, and TSH were measured by radioimmunoassay and caffeine by high pressure liquid chromatograph. GH was increased at all times and all doses after a single injection of caffeine. After chronic therapy, the increase in GH was small, suggesting depletion of pituitary reserve. A high dose of caffeine had a biphasic effect on T4 with an increase at 4 h and a decrease at 24 h. Thyrotropin-releasing hormone (TRH)-induced TSH release at 24 h was not influenced by caffeine administration. Chronic caffeine therapy stimulated both T4 and TSH; however, TRH-stimulated TSH release was decreased, suggesting that chronic therapy may blunt pituitary TSH response.

Animals↗