http://evolve.elsevier.com/McCuistion/pharmacology
A nurse who is providing care to children must make certain adaptations in assessment, treatment, and evaluation of nursing care because of the physiologic, psychological, and developmental differences inherent in the pediatric population. This is especially true in the science of pharmacology, in both the administration of drugs to children and evaluation of the therapeutic and adverse effects of a drug. This chapter addresses pediatric nursing adaptations and discusses the impact of a child’s growth and development on many aspects of pharmacology: pharmacokinetics, pharmacodynamics, dosing and monitoring, methods of drug administration, and nursing implications.
Pediatric pharmacology is limited to available research in the provision of dosing protocols, safe practices, key assessments, and important nursing implications. Most available information about drugs is derived from studies that use adult samples, small sample sizes, or samples with healthy children. Few studies have been conducted to determine the effectiveness of drugs in the pediatric population. Generalizing the results of studies using adult patients to pediatric populations may result in serious errors and ignores the impact of growth and development on pharmacology.
Patient SafetyPreventing Drug Administration Errors in Pediatric Pharmacology
• Owing to developmental factors and smaller body size, infants and young children may receive drug dosages much different from those of adults. Careful calculations, double-checking math, and checking with another registered nurse can prevent errors in drug administration.
• Ensure that families understand the units of measurement for a drug. Confusion may occur with the discussion of metric, household, and other measurement systems.
• For safety when administering injectable drugs to children, use the smallest syringe that ensures the most exact measurement of the drug.
• Use the correct drug and procedure to ensure safe dosing. Dilutions, different concentrations, and different solutions of a prescribed drug can complicate administration of appropriate pediatric dosages.
• Infants and children may not be able to confirm identity, allergies, or drugs. The nurse must be positive of such information before drug administration.
• Nurses must be vigilant for severe side effects or adverse reactions to drugs because information on pediatric drug response is limited.
• Regulatory agencies caution that drug administration errors are more common in pediatric patients, which warrants increased precautions in drug administration.
Research related to pediatric patients is limited because of several factors. Research risks and obtaining informed consent make it difficult to recruit a pediatric sample. Parents and guardians are reluctant to provide permission for children to participate in research studies because of the risk involved and the potentially invasive nature of data gathering. Pharmaceutical companies invest fewer resources in pediatric drug research because of the smaller market share afforded to pediatric drugs. However, many contend that lack of pediatric data reflects lack of due diligence, especially when drugs are administered to pediatric patients without supporting research data on which to base safe practices. As a result, less is known about the effects, uses, and dosages of pediatric drugs, and nurses must investigate pediatric drugs carefully to provide knowledgeable nursing care for children.
Closely aligned with the conflicts that affect pediatric pharmacologic research are those associated with drug labeling and dosing instructions. Because many drugs have not undergone the clinical trials required for federal approval, they have not been approved for pediatric use. Safe use for children may be guided by small studies or the judgment of the clinician and may be based on anecdotal evidence rather than scientific study. These conflicts have generated new legislation designed to protect pediatric patients and provide health care professionals with better information and resources.
Despite the permanent reauthorization of the Pediatric Research Equity Act (PREA) in 2012, which requires drug manufacturers to study pediatric drug use and offers incentives for pediatric pharmacology research, only half of all drugs carry federally approved indications for use in children. This means many drugs prescribed for children are being prescribed off label, which means the drug is being used for some purpose for which it has not been approved. Current research agendas reinforce the need for pediatric drug research and establishment of safe guidelines for pediatric drug dosing, administration, and evaluation.
Pharmacokinetics
Significant differences exist in drug pharmacokinetics for pediatric patients versus adults. These distinctions stem from differences in body composition and organ maturity and appear to be more pronounced in neonates and infants but less significant in school-age and adolescent children. Pharmacokinetics may be defined as the study of the time course of drug absorption, distribution, metabolism, and excretion.
Absorption
The degree and rate of drug absorption are based on factors such as age (Table 5.1), health status, weight, and route of administration. As children grow and develop, the absorption of drugs generally becomes more effective; therefore less developed absorption in neonates and infants must be considered in dosage and administration. In contrast, poor nutritional habits, changes in physical maturity, and hormonal differences during the adolescent years may cause slowing of drug absorption. Hydration status, presence of underlying disease, and gastrointestinal (GI) disorders in the child may be significant factors in the absorption of drugs.
TABLE 5.1
| Classification | Age |
| Term neonate | Birth at 38 or more weeks’ gestation to 27 days |
| Infant/toddler | 28 days to 23 months |
| Children | 24 months to 11 years |
| Adolescent | 12 years to 16 or 18 years (regional difference) |
From U.S. Food and Drug Administration. (2014). Pediatric exclusivity study age group (C-DRG-00909). Retrieved from http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/DataStandardsManualmonographs/ucm071754.htm
Drug absorption is initially influenced by the route of administration. For oral drugs, conditions in the stomach and intestine such as gastric acidity, gastric emptying, gastric motility, GI surface area, enzyme levels, and intestinal flora all mediate drug absorption. Lack of maturation of the GI tract is most pronounced in infancy, making the neonatal and infancy periods those most affected by changes in absorption physiology. Gastric pH is alkaline at birth; acid production begins in the neonatal period, and gastric acid secretion reaches adult levels around 2 to 3 years of age. A low pH, or acidic environment, favors acidic drug absorption, whereas a high pH, or alkaline environment, favors basic drug formulations; therefore differences in pH may hinder or enhance drug absorption. Gastric emptying and GI motility are unpredictable in neonates and infants; however, it approaches that of adults between 6 and 8 months of age. Gastric emptying is affected by feeding, and breast-fed infants have faster gastric emptying than formula-fed infants. Unpredictable GI motility may hinder or enhance absorption of oral drugs, depending on the usual site of chemical absorption.
Intestinal surface area in neonates does not reach that of adults until 20 weeks; prior to this, the reduced surface area leads to reduced drug absorption. Immature enzyme function may also affect drug absorption; neonates have inadequate production of bile salts and pancreatic enzymes, which leads to reduced absorption of lipid-soluble drugs. Intestinal microbial colonization begins in the first few hours after birth and is influenced by gestational age and whether the neonate is breast or formula fed; GI microbial colonization reaches adult levels in adolescence. All of these factors must be considered when assessing the effectiveness of drugs administered by the oral route.
For drugs administered via the subcutaneous (subcut) or intramuscular (IM) routes, absorption occurs at the tissue level. The level of peripheral perfusion and effectiveness of circulation affects drug absorption. Conditions that alter perfusion—dehydration, cold temperatures, and alterations in cardiac status—may impede absorption of drugs in the tissues. Intravenous (IV) drugs are administered directly into the bloodstream and are immediately absorbed and distributed.
Distribution
Drug distribution is affected by factors such as body fluid composition, body tissue composition, protein-binding capability, and effectiveness of various barriers to drug transport. In neonates and infants, the body is about 75% water, compared with 60% in adults. This increased body fluid proportion allows for a greater volume of fluid in which to distribute drugs, which results in a lower drug concentration. Until about age 2 years, the pediatric patient requires higher doses of water-soluble drugs to achieve therapeutic levels. Younger patients also have higher levels of extracellular fluids, which increases the tendency for children to become dehydrated and changes the distribution of water-soluble drugs. Compared with older children, neonates and infants have fat stores with an increased ratio of water to lipids, which alters the distribution of some lipid-soluble drugs. Close monitoring of drug levels (e.g., anti-epileptic drugs) can help ensure drug safety.
To varying degrees, drugs become bound to circulating plasma proteins in the body. Only drugs that are free, or unbound, are available to cross the cell membrane and exert their effect. Neonates and infants have decreased protein concentrations compared with adults, and they have fewer protein receptor sites with an affinity for drug binding in the first 12 months after birth; this results in higher levels of unbound drug and an increased risk of drug toxicity.
In neonates, high bilirubin levels may pose a health risk related to drug administration. Bilirubin molecules may bind with protein receptor sites, which makes the sites unavailable to drugs or displaces drugs from binding sites, allowing large amounts of drug to remain free and available for effect. When drugs are prescribed to neonates, dosages must be decreased and closely monitored to both avoid adverse effects and ensure therapeutic effectiveness.
Anatomic barriers to drug distribution, such as the blood-brain barrier (BBB), must be considered when drugs are administered to pediatric patients. This barrier in neonates is relatively immature and allows drugs to pass easily into central nervous system (CNS) tissue, thereby increasing the likelihood for toxicity. As a child matures, the BBB becomes more impervious to drugs, and drug dosages must be titrated accordingly.
Metabolism
The metabolism of drugs depends greatly on the maturation level of the pediatric patient and varies from child to child. Metabolism is carried out primarily in the liver, with the kidneys and lungs playing a small part in metabolism. Infants have reduced hepatic blood flow and drug-metabolizing enzymes; however, by the time they reach 1 year of age, hepatic blood flow has reached that of an adult. Whereas drug-metabolizing enzymes reach an adult level at around age 11, it is important to understand that the isoenzymes involved in the cytochrome P450 system—CYP1, CYP2, and CYP3 (Table 5.2)—develop at different rates and demonstrate individual variation. Drug prescribing should be based on therapeutic effect and drug concentration. Such differences in drug metabolism, as with other pharmacokinetic factors, reinforce the importance of the nurse evaluating therapeutic effects and monitoring the adverse effects of drugs.
Excretion
Renal excretion is the predominant means of drug elimination. The glomerular filtration rate (GFR) in term neonates is roughly 30% that of adults. During infancy, the GFR rises, and by 12 months, it reaches adult levels. Nurses must carefully monitor renal function, urine flow, and drug effectiveness to evaluate the impact of drug administration on patient status.
Pharmacodynamics
Pharmacodynamics refers to the mechanisms of action and effects of a drug on the body and includes the onset, peak, and duration of effect of a drug. It can also be described as the intensity and time course of therapeutic and adverse effects of drugs. The variables of pharmacokinetics—absorption, distribution, metabolism, and excretion—all affect the parameters of pharmacodynamics. These processes determine the time a drug begins to function, reaches its peak, and sustains its length of action. Variables such as organ function, developmental factors, and administration issues affect drug pharmacodynamics and drug half-life in pediatric patients (Table 5.3), and these have an impact on drug dosing.
Nursing Implications
Pediatric Drug Dosing and Monitoring
Because of the changes in pharmacokinetics and pharmacodynamics inherent in pediatric patients, a key nursing role is to monitor the patient for therapeutic effect and adverse reactions. The processes described earlier in the chapter may be measured using plasma or serum drug levels, which indicate the amount of drug in a patient’s body. The therapeutic ranges established for many drug levels are based on adult studies; therefore close monitoring of serum drug levels can assist in establishing appropriate dosages, schedules, and routes of administration. Monitoring can also assist in indicating when the dose is subtherapeutic or becomes toxic. Serum blood levels are not available for all drugs, so patient clinical responses to drugs are especially important when monitoring drug effects.
The calculation of pediatric dosages is based in part on U.S. Food and Drug Administration (FDA) recommendations; as a result of the Best Pharmaceuticals for Children Act (BPCA) and PREA, pediatric dosing is now available for over 450 drugs. For those drugs without pediatric dosing schedules, dosing is based on approved protocols, research studies, and provider experience. Drugs for pediatric patients are ordered based on either the child’s weight in kilograms (mg/kg) or body surface area (BSA; or mg/m2). Body surface is based on a percentage of adult surface area (1.73 m2). Dosing must also consider the individual child’s status, including age, organ function, health, and route of administration.
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