Objectives: The purpose of this article is to educate nurse practitioners about prescribing principles for children. After reading this article, the nurse practitioner should be able to:
Discuss a rational approach for writing prescriptions for children.
Discuss appropriate drug selection for pediatric patients.
State the components involved in establishing efficacy criteria for prescribed drug therapy.
Discuss how to determine criteria for discontinuing drug therapy.
Prescribing medications for patients of any age requires thorough knowledge of the pharmacokinetic and pharmacodynamic profile of each drug. Pediatric patients are especially vulnerable to adverse events and problems due to the lack of pediatric labeling information on the majority of prescription medications. Approximately 80% of drugs on the market do not have pediatric dosing or safety information.1
Although medications are extensively studied prior to marketing, this research is mainly conducted in adult populations. Information from the adult literature often cannot be extrapolated to children, due in part to physiologic differences among neonates, infants, children, adolescents and adults.2 Despite this, many drugs with no established parameters for children are prescribed every day to treat pediatric patients. The simple task of writing a prescription can have a profound impact if differences in pharmacokinetic and pharmacodynamic principles between children and adults are not clearly understood.3
Appropriate Drug Selection
When initiating drug therapy, several questions must be answered. The first are obvious. Which drug? What dose? Which route of administration?
But are these questions or their answers really that simple? For example, will the drug prescribed to treat a symptom interfere with making a diagnosis? What formulation is available for this drug? Is it appropriate for this patient? How much does it cost? Will this patient be able to afford it? These questions and others must be answered for each patient. Often, the answer changes between patients - and even between visits for the same patient.
Before empirically starting a medication, know and document the reason for its use. Develop a differential diagnosis list so that the selected drug therapy is as specific as possible to the most likely diagnosis. A differential diagnosis list also helps avoid the use of a medication that could interfere with making the correct diagnosis.
For example, if a patient is admitted with agitation, prescribing a sedative may not be the most appropriate choice, especially if he or she has a history of head trauma or other central nervous system conditions. These drugs may mask signs and symptoms used to make a definitive diagnosis, or interfere with assessment of the condition's progression.
Other examples are prescribing a nonsteroidal anti-inflammatory agent for pain, which would mask signs of inflammation, or prescribing a systemic steroid for croup, which would mask the signs of leukemia. Using a working diagnosis prior to initiating drug therapy may eliminate the drug that would confound a diagnosis.
The Drug of Choice
Many medical references and guidelines provide a drug of choice to treat nearly every ailment. However, selecting the so-called drug of choice requires consideration of the patient's characteristics as well as the drug's characteristics. Not every recommended drug is a drug of choice for every patient.
For example, product formulation will dictate drug selection. Infants obviously cannot swallow capsules, and young children cannot take dry powder inhalers because they lack sufficient inspiratory effort. However, if the capsule is not an extended-release formulation, the contents may be mixed in milk or sprinkled on food. Young children diagnosed with asthma may use a meter-dose inhaler with a spacer, which is not dependent on inspiratory effort or coordination.
Other patient characteristics to consider include comorbid conditions such as renal or liver failure, along with patient allergies. All of these factors influence the drug of choice for each patient.
Determining the correct dose is as important as deciding on the appropriate drug. Incorrect dosing can result in adverse events and complications.
For best results, individualize the dose for each patient. When selecting the correct dose for a child, consider the disease being treated, comorbid conditions, concomitant medications, age, size and maturation of organ development. The majority of drugs used in pediatric patients are dosed according to the patient's body weight with a mg/kg dose.
Neonates, on the other hand, are dosed based on gestational or postnatal age as well as body weight, in consideration of the maturation of drug elimination routes. Thus, dose adjustments for neonates may be based on body weight, age, renal function or hepatic function.
Two important drug disposition processes to consider when selecting appropriate drug therapy are hepatic metabolism and renal excretion of medications.
Although almost all metabolic processes of the liver can be demonstrated in infants, the rates are by far slower in newborns (especially preterm) than in older children or in adults. The direct result of this immaturity of metabolic drug degradation is a prolonged drug half-life, which is inversely correlated with clearance rate.
Clinically, this means that in newborns and small infants, metabolically eliminated drugs tend to stay in the body longer. As a result, therapeutic concentrations and prevention of toxicity are achieved with lower doses, longer dosing intervals or both. Chloramphenicol toxicity in newborns (gray baby syndrome) is a prime example of enzyme deficiencies in the neonatal liver that prevent adequate metabolization of certain drugs.
Impaired renal excretion can also have a devastating impact. At birth, the glomerular filtration rate is much lower than in older infants, children and adults. Calculated on the basis of surface area, glomerular filtration in the neonate is only 30% to 40% of the adult value. During the first week of life, the glomerular filtration rate and renal plasma blood flow increase by 50% from the first day. By the end of the third week, glomerular filtration is 50% to 60% of the adult value. By age 6 months to 12 months, it reaches adult values. Therefore, drugs that depend on renal function for elimination are slowly cleared from the body in the first weeks of life. Thus, using the standard dose may not be applicable.
Although body weight might produce such a calculation, a pediatric dose should not exceed the normal adult dose. In an obese child, lean body mass - rather than the patient's actual body weight - may be used to calculate a correct dose. In some cases, a patient's body surface area may be used to determine the dose; this is common with many chemotherapeutic agents.
Another factor to evaluate when selecting the appropriate dose is the use of a loading dose. Some drugs may require a loading dose to reach a therapeutic concentration more rapidly. In the majority of those cases, the drug has a long half-life and would require days to weeks to reach a steady state concentration. For example, half-life of phenobarbital in the neonate is approximately 120 hours. Two to 3 weeks are therefore required to obtain steady state concentrations. By administering the maintenance dose rather than a loading dose to a neonate, an adequate concentration for seizure control may not be obtained quickly enough. Therefore, a slowly infused loading dose of 15 mg/kg to 20 mg/kg may be used to achieve a serum concentration of approximately 20 mg/L to 30 mg/L more quickly.
The Dosing Interval
The half-life of a drug helps determine the dosing interval. The half-life is the time required for the plasma concentration of the drug to decrease by 50%. It indicates how quickly a drug is removed from plasma, and this determines how often a dose is required.
Half-life is influenced by the patient's renal or hepatic function. The dosing interval for a drug is not always the same in a neonate, child and adult due to clearance rates.
For example, theophylline may be administered to an adult three times a day, but it is administered to a child four times a day. On the other hand, theophylline may be administered every 8 or 12 hours to a neonate to treat apnea of prematurity. The differences in the dosing interval with this agent are due to slower clearance in adults and an even slower clearance in neonates. The average half-life of theophylline is 4 to 5 hours for a child, 8 hours for nonsmoking adults and more than 10 hours for a neonate.
In addition to the half-life, convenience of dosing should be considered. Common dosing intervals are every 6, 8, 12 or 24 hours. Using uncommon dosing intervals such as every 18 or 36 hours is problematic for patients and parents. To achieve a convenient regimen that promotes compliance, choose a dosing interval that does not interfere with sleeping or, if possible, school hours.