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stomach of infants at less than 32 weeks' gestation. Acid initially is secreted within the first few hours after birth, reaching peak levels within the first 10 days of life. It decreases during the next 20 days of extrauterine life. Gastric acid secretion approaches the lower limits of adult values by 3 months of age. The initiation of acid secretion is often delayed in infants with delayed initiation of oral feedings, such as extreme preemies and those with anomalies of the gastrointestinal tract.

Gastric emptying time in infants is related to their age and to the type of formula they receive. Formulas containing long-chain fatty acids will delay gastric emptying. Both gastric emptying time and small-intestine peristalsis tend to be slow until the later part of the first year of life. In children aged 2 to 12 years gastric emptying time dramatically increases, as does splanchnic blood flow. These physiological changes result in faster drug absorption and increased peak blood concentrations of drug. The decreased small intestine transit time during this period may result in decreased absorption of some drugs. Because of low blood flow through muscles in the neonatal period, drugs administered intramuscularly are absorbed erratically.

Percutaneous drug absorption can present special problems in newborns, especially in preterm infants. While the skin of a newborn term infant may have the same protective capacity as the skin of an adult, a preterm infant will not have this protective barrier until after 2 to 3 weeks of life. Excessive percutaneous absorption has caused significant toxicity to preterm babies. Absorption of hexachlorophene soap used to bathe newborns has resulted in brain damage and death. Aniline dyes on hospital linen have caused cyanosis secondary to methemoglobinemia, and EMLA (lidocaine/prilocaine) cream may cause methemoglo-binemia when administered to infants less than 3 months of age.

Distribution

The total body water of prematures, newborns, and infants is significantly greater than it is for older children and adults. This increased total body water increases the volume of drug distribution for water-soluble compounds. As a consequence, there is a need to administer loading doses of some drugs. Differences in total body water are basically insignificant after the first year of life. Newborns have decreased body fat and therefore less storage ability for fat-soluble drugs.

Newborns, especially prematures, have decreased plasma albumin and total plasma protein concentrations. In addition, albumin from these patients shows a decreased drug-binding affinity. This may result in increased plasma levels of free drug and the potential for toxicity. In the past, concerns were raised that certain drugs, such as sulfonamides, could displace endogenous substances, like bilirubin, from albumin-binding sites. Theoretically, such an interaction would increase the risk for kernicterus. Although this belief has been challenged recently, reluctance to treat newborns with sulfonamides persists.

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