Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rational pharmacotherapy is dependent upon an understanding of the clinical pharmacokinetic and pharmacodynamic properties of the drugs employed. Although the available data on drug biodisposition and action in the neonate have increased considerably in the last few years, pharmacokinetic-pharmacodynamic interactions for many drugs remain poorly understood. The ontogeny of drug absorption, distribution, metabolism, and elimination are addressed in this review. Drug absorption from any site depends upon both the physicochemical properties of the drug and a variety of patient factors. Absorption of orally administered drugs may be affected by changes in gastric acidity and emptying time as well as by bile salt pool size, bacterial colonisation, and extraintestinal disease states such as congestive heart failure. Factors affecting drug absorption following intramuscular, percutaneous, and rectal administration are also discussed. Drug distribution in the neonate is influenced by a variety of important and predictable age-dependent factors. The developmental aspects of protein binding and body water compartments are described. Additionally, hepatic drug metabolism assumes an important role in understanding the pharmacokinetic and pharmacodynamic properties of many compounds. Certain biotransformation pathways, including hydroxylation by the P450 mono-oxygenase system and glucuronidation, demonstrate only limited activity at birth, while other pathways, such as sulphate or glycine conjugation, appear very efficient at birth. Elimination of drugs excreted unchanged in the urine is dramatically reduced in the newborn, compared with older infants and children, due to immaturity of both glomerular filtration and tubular secretory processes. The glomerular filtration rate remains markedly reduced prior to 34 weeks gestational age, increasing as a function of post-conceptual age until adult values are achieved by approximately 2.5 to 5 months of age. Tubular secretory capacity is also limited at birth, approaching adult values by approximately 7 months of age. Published reports describing the pharmacokinetics and pharmacodynamics of commonly used drugs in the neonatal period, as well as differences in drug biodisposition among premature infants, full term neonates, and older infants and children, are reviewed. Our recommendations for neonatal drug therapy are based upon a critical interpretation of these data, an understanding of fetal development and maturational processes, and an understanding of how disease states may affect drug biodisposition in the neonate.
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PMID:Principles of drug biodisposition in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface (Part I). 329

Water metabolism is a major problem in infants of very low birth weight. Their surface is proportionally larger, they have a relatively low intracellular water volume and a high extracellular and total body volume. Kidney function is immature compared to bigger infants, and the neuroendocrine function is also immature. Finally the large surface and the high skin permeability causes a very high insensible water loss in the early neonatal period. Water imbalance presents itself as either dehydration or overhydration. Dehydration gives poor peripheral--and renal circulation and thereby decreased renal function with acidosis. Furthermore hyperosmolar dehydration will give increased hematocrit and blood viscosity and hyperbilirubinaemia. Excessive administration of water will give oedema and congestive heart failure and possibly an increased risk for patent ductus arteriosus, bronchopulmonal dysplasia and necrotising enterocolitis. The evaporative water losses varies according to the thermal environment and air humidity and it is therefore impossible to give narrow limits for the daily water intake. Clinical examination, frequent controls of body weight (twice daily) and measurements of urine volume and osmolarity serve as guide lines. Yet inappropriate secretion of ADH may confuse the value of measuring urine osmolarity. Finally a neonatal weight loss of 5-10% may be beneficial as a decrease in extracellular water may lessen the working load of the heart and therefore possibly lessen the risk for a patent ductus. Renal immaturity in handling sodium reabsorption on the other hand, will often give an excessive dehydration. For this reason about 2 mmol Na/kg body weight should be given daily to very low birth weight infants from the fourth day of life to the 3rd-4th week if the baby is on human milk or a low salt formula.
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PMID:Water--the major nutrient. 2475 24

Patent ductus arteriosus (PDA) is one of the most common congenital heart defects, accounting for 5%-10% of all congenital heart disease in term infants. The occurrence of PDA is inversely related to gestational age and weight, with an even greater incidence in preterm infants. The maintenance of ductal patency is essential for the normal development of the fetus. In the neonate, however, persistent patency of the ductus arteriosus (DA) is associated with significant morbidity and mortality. Normally, at birth, the DA constricts, resulting in intraluminal ischemic hypoxia, which eventually leads to closure and remodeling of the ductus. PDA in term infants is usually associated with a functional defect, whereas in preterm infants it is associated with immaturity. Normal physiologic mechanisms contributing to closure - oxygen tension and decreased prostaglandins-are altered in prematurity. Clinical signs of ductal patency include murmur, tachycardia, bounding peripheral pulses, and congestive heart failure and associated symptoms. Symptoms are not always present; therefore, diagnostic imaging is critical if a PDA is suspected on clinical grounds. Three management strategies are currently available for PDA: fluid restriction and diuretics (as clinically appropriate), medical intervention, and surgical ligation. Pharmacologic closure can be achieved via administration of intravenous indomethacin or ibuprofen lysine. While both agents have shown similar efficacy, ibuprofen lysine has demonstrated an improved safety profile, particularly in terms of renal effects, compared to indomethacin.
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PMID:Patent ductus arteriosus: an overview. 2305 49