Pediatric pharmacology (New York, N.Y.)最新文献

The purpose of this investigation was to assess the extent of biotransformation of drugs by the human placenta during their transfer from the maternal to the fetal circulation. Propoxyphene was used to determine N-demethylation, and acetaminophen served as a substrate for glucuronide and sulfate conjugation. Human full-term placentae were dually perfused in vitro, with one or the other drug being added to the maternal circulation. Propoxyphene and acetaminophen concentrations reached an essentially constant fetal/maternal ratio within 1 hour, with a half-time of about 20 minutes. The concentrations of both drugs in the placental tissues were higher than in the perfusion fluids; this accumulation was particularly pronounced in the case of propoxyphene. No metabolites of either drug were found in the maternal or fetal circulations, but norporpoxyphene, the N-demethylated metabolite of propoxyphene, was detected in placental tissue.

The effects of clonidine and hydrochlorothiazide on cognitive function were studied in hypertensive adolescents requiring pharmacologic therapy for blood pressure control. Twenty-four adolescents with persistent blood pressure elevation (greater than 95th%) on placebo were randomized double blind to clonidine or hydrochlorothiazide treatment. A battery of cognitive tests were performed during the placebo phase and after 16 weeks of active therapy. Antihypertensive therapy resulted in significant blood pressure reduction (p less than .01). A slight interactive effect was observed in arithmetic performance (p less than .05). All other parameters of cognitive function were not affected by either treatment.

Pulmonary extraction of radiolabeled norepinephrine (NE) was evaluated in newborn rabbits aged 1 to 3 days. Twenty pups were raised from birth in an hypoxic environment (FiO2 = 0.16-0.17) and 10 were raised in room air for study as controls. NE extraction was measured using an isolated, perfused lung technique. In hypoxic animals, average percent removal of NE was significantly reduced (p less than 0.05) as compared to controls while pulmonary pressures were increased (p less than 0.05) compared to controls. The data suggest that hypoxia reduces the ability of the lung to clear norepinephrine. This may be a factor in systemic and pulmonary vasomotor responses to hypoxia.

In previous studies, we found that Sprague-Dawley rats injected with 6-mercaptopurine monohydrate (6-MP) at 2 mg base/kg sc daily from 2 to 22 days of age had atrophy of thigh and sublumbar muscles when killed at 16 months of age. The first sign of this muscle atrophy was detected grossly (flattened croup with or without paresis) at 12 months of age. In one experiment of the present work, using the same treatment in rats as above, we found that the earliest onset of muscle atrophy observed by light microscopy occurred at 2 months of age. By 4 months the atrophy could be detected grossly. The atrophy did not uniformly involve all muscles of the hindquarters; the thigh (especially the semitendinosus), leg (soleus but not the extensor carpi group), and lumbar vertebral (including the psoas) muscles were involved. Foreleg (biceps), intercostal, and tongue muscles as well as the sciatic nerve and internal organs appeared unaffected. In another experiment, weanling Sprague-Dawley rats given large daily doses of 6-MP from 25 to 45 days of age had normal muscles when killed at 8 months. In a third experiment, Wistar rats injected with 6-MP (2 mg base/kg sc) daily from 2 to 22 days of age and killed at 6 months had muscle atrophy similar to that seen in Sprague-Dawley rats. In the last experiment, mice and hamsters given large daily doses of 6-MP from 2 to 22 days of age had normal muscles when killed at 10 months. It appears from these results that the 6-MP-induced muscle atrophy occurs only after treatment during the neonatal period and that the atrophy may be species specific.

Antepartum administration of aminophylline (AF) to pregnant animals resulted in accelerated and increased pulmonary maturation as well as in decreased morbidity and mortality from RDS in premature offspring. The present study was undertaken to evaluate the effect of antenatal AF treatment on the frequency of RDS among premature infants born of women who were treated (18) and to compare this group with betamethasone (GC) treated group (16 women). No statistical significant differences were noted between the AF and GC groups in the incidence of RDS (AF = 11.0%; GC = 0%) and in the frequency of perinatal deaths (AF and GC = 0%). Only a significant difference was noted between the AF group and the GC group in the incidence of neonatal signs of infection (AF = 0%; GC = 50%). The authors conclude that antenatal AF treatment may be as effective as GC in the prevention of RDS in premature infants with, for the moment, no side effects.

Indomethacin is commonly coadministered with digoxin for the treatment of patent ductus arteriosus (PDA) in preterm infants. The combination of digoxin that is eliminated almost exclusively by the kidney and indomethacin, which tends to reduce renal function, has potential hazards. We report 11 preterm infants (gestational age 25-33 week) treated with digoxin for PDA in whom a standard indomethacin therapy (mean of total dose = 0.32 mg/kg) resulted in a significant elevation of serum digoxin to potentially toxic levels (from 2.2 +/- 0.7 ng/ml to 3.2 +/- 0.7) (P less than 0.001). This phenomenon correlated well with decreased urine output (from 86 +/- 34 ml to 43 +/- 24 per 24 hour) (P less than 0.001) following indomethacin. No significant change was found in serum creatinine concentration pre- and post-indomethacin. Digoxin half-life was significantly prolonged (mean 97 +/- 17 hour) following indomethacin therapy as compared with an age matched control group (mean half-life 43 +/- 19 hour) (P less than 0.05). Our data suggest that when indomethacin is added to digoxin therapy, the digoxin dosage should be reduced by 50% until urine output and digoxin serum levels can be better assessed.

A girl with secondary amyloidosis as a complication of juvenile rheumatoid arthritis was administered dimethyl sulfoxide by topical application to the skin. Her gastrointestinal symptoms and massive proteinuria improved. Decreased left ventricular function and creatinine clearance also improved remarkably. The favorable effect of dimethyl sulfoxide in this single patient deserves further study in a controlled trial.

We present a case of neonatal renal failure following a pregnancy complicated by hypertension treated with captopril. Clinical investigations showed structurally normal kidneys, suggesting a renal dysfunction other than that seen with the more common causes of neonatal renal failure. Recent animal and human data would support our hypothesis that transplacental captopril could have produced the clinical picture seen in our patient. Our findings do not unequivocally implicate captopril as the offending agent; however, since captopril is not considered to be teratogenic, a more widespread use may be anticipated in pregnancies complicated by severe hypertension. Surveillance of such pregnancies may yield more information regarding the above association.

Heart rate, demeanor, and facial flushing following intramuscular injection of atropine or glycopyrrolate were compared in 80 paediatric patients under 1 year of age. No significant differences occurred between the two drugs in the doses used. Neither was there any difference in drug response between those children aged under 2 months and the other patients in the study.