Question

In 250 words Describe considerations in dealing with pediatric patients and medication administration. In what ways are pediatric patients’ bodies different in terms of processing medications? How can you ensure safe medication administration for pediatric patients? What should you do if your dosage calculation is not considered safe according to the medication’s package insert

Answer 1

Pediatric patients experience unique differences from the adult population in pharmacokinetic parameters and, consequently, require individualized dosing. In medication, age affects not only the amount of medication to take, but also the form in which the medication will be prescribed. Patient age is an important factor in the manufacturing and prescribing of drugs. When developing formulations for pediatric and geriatric populations, manufacturers must give special consideration to dysphagia, dosing and physiological changes. Medications useful in pediatric medicine often lack a therapeutic indication and dosing guideline for this population. In addition, the absence of an available pediatric dosage form for some medications increases the potential for dosing errors and may produce serious--sometimes fatal--complications in young patients. It is important to select an appropriate medication and dose based on individualized pharmacokinetic considerations: one must evaluate a patient's age, size, and level of organ maturity, and not simply administer a "small adult" dose. Thus specific dosing guidelines and useful dosage forms for pediatric patients need to be developed in order to optimize therapeutic efficacy and limit, or prevent, serious adverse side effects.

Dysphagia, or trouble swallowing, is prominent in geriatric and pediatric populations. Because dysphagia is such a common problem, there is a need for medications in formulations other than oral tablets and capsules. Pediatric patients prefer liquid medication, but geriatric patients prefer small tablets and sprinkles. Medication that comes in these preferred forms improves compliance and eliminates the need to cut or crush large tablets.

Drug companies must give special consideration to physiological changes when making formulations for pediatric and geriatric populations. Formulations for pediatric and geriatric populations must take dysphagia, dosing and physiological changes into account. Orbis Biosciences keeps these patient-centric ideas in mind when developing drug formulations for age-specific populations.

Differences in age, body size, disease states, and physiology lead to differences in the way the body handles the drug (phrmacokinetics), the effects of the drug (pharmacodynamics), and side effects in this population. The age-related changes in absorption, distribution, metabolism, and elimination of drugs further affect where and how much of each drug is deposited in the body and ultimately lead to pediatric drug dosing.

Absorption
The route of administration influences absorption of a drug. The types of administration include the following: via the skin, gastrointestinal (GI) tract including the rectum; intramuscularly (IM); and intravenously (IV).

First, absorption through the skin is related to the thickness of the skin. Since the newborn infant begins life with skin that is much thinner than the adult skin, drugs may be absorbed more quickly than in adults, which may lead to toxicity. For example, side effects from skin applications of iodine (an antibacterial cleanser), hexachlorophene (an antibacterial cleanser), salicylic acid ointments (for removal of warts), and hydrocortisone creams have occurred in neonates and infants. Differences between pediatric patients and adults must also be considered when using the GI tract as a route of administration for drugs. For example, for the first 10-15 days after birth, a newborn has a relative lack of stomach acid. A child does not have adult values of stomach acidity (pH) until two years of age. This factor may lead to increased absorption of certain drugs like penicillin and ampicillin. Furthermore, stomach emptying in the newborn is irregular, unpredictable, and prolonged, reaching adult values at about six- to eight months of age. The slower emptying time leads to increased absorption of various medications because of increased contact time with the GI tract. Thirdly, muscle (IM) absorption is erratic in newborns because of relative lack of muscle and fat tissue. Also, IM administration of drugs is avoided because it may damage immature tissues. Similarly, rectal absorption is not reliable except for rectal Valium for seizures.

Distribution
Drug distribution to various parts of the body differs between adults and newborns. Distribution of drugs is influenced by total body water, protein-binding of drugs, and changes in the makeup and size of organs. An adult’s total body water accounts for approximately 60% of body weight. The preterm infant may be composed of as much as 90% water and a normal newborn about 75% water. In contrast to body water, however, fat stores represent a very small percentage of body weight in preterm infants, generally in the range of 1-5%. Fat stores comprise about 15% of body weight in the term infant, which is similar to the adult. Depending on how water- or fat-soluble a medication is, it will be distributed differently in the pediatric patient than in an adult. In addition, because of their lower protein concentrations, newborns have low binding of drugs to blood proteins as compared to adults. This means that more of the drug is available in the unbound and active form, a phenomenon that could lead to toxicity of certain drugs. Furthermore, the blood-brain barrier is immature in the infant. (Blood vessels of the brain are very selective in allowing material to pass from blood into the brain, hence the term blood-brain barrier.) This barrier allows for greater distribution of drugs into the central nervous system in the infant. All of these factors influence how a drug is distributed in the body.

Metabolism
Metabolism refers to the changes in the structure of the drug that help the body eliminate that drug. (drugs are foreign substances, and the body will try to do what it can to eliminate them) The main organ responsible for metabolism of drugs is the liver. Metabolism of drugs by the liver changes significantly with age. Newborns metabolize drugs at a rate several times lower than that observed in adults; this is due to the relative lack of maturation of metabolic (enzyme) machinery at different ages for different metabolic pathways. Although most drugs are metabolized to less active forms, some may be transformed to active metabolites. An example is the conversion of theopylline (an asthma and emphysema medicine) to caffeine. This is due to one of the metabolic pathways called methylation reactions, which is generally low in adults, but high in term infants.

Elimination
Elimination of drugs generally depends on kidney function, which also changes widely in early childhood. There is a decreased clearance of drugs in newborns relative to adults. Overall kidney function increases with age. Therefore, as the kidney function matures, there may be a shift from potential drug overdose to potential underdose for some drugs, such as theophylline.

Drug administration
The administration of drugs to children requires special knowledge and expertise. For administration of oral medications, caution must be taken not to choke the child. Liquid medications should be placed on the middle of the tongue or in the cheek area by using a dropper. Usually the taste of medicine is disguised by using juice, applesauce or ice cream. Children should always be praised for cooperating in taking their medications. To administer ear drops in children up to three years of age, the external ear is held down and out, which helps deliver the drug to the middle ear. In older patients, the ear is held up and back to straighten the ear canal. To administer nose drops, the child is placed on his/her back across a bed with shoulders over the edge so that the head is lower than the body. The child is kept in this position for 2-5 minutes after the medication is administered. To administer eye drops, caution should be taken to prevent injury to the eye. The lower lid must be gently pulled down by the thumb, and the hand holding the dropper should be balanced on the head of the child so that the hand moves with the head in case the child turns or jumps.

Drug toxicity unique to children
Sulfonamides (sulfa drugs) displace bilirubin (a byproduct of red blood cells that causes jaundice in newborns and adults) from its binding sites. This leads to high levels of bilirubin in the blood, which may cause a condition called kernicterus in infants, which is a non-reversible brain damage due to high bilirubin levels in brain. The antibiotic chloramphenicol, given to newborns, causes gray baby syndrome, characterized by vomiting, ashen color, cardiovascular collapse, and death. This is caused by the inability of the newborns to metabolize the drug leading to accumulation of the drug.

Quinolones (a class of antibiotics including Cipro) have shown to cause cartilage defects in beagle dogs and are generally avoided in pediatrics, who have growing cartilage. Because they cause permanent discoloration of the teeth and enamel and affect skeletal development and bone growth, tetracyclines are avoided in children less than 9 years of age. Aspirin causes Reye's Syndrome, a condition characterized by liver injury, low-blood sugar, and vomiting in children with chicken pox or flu symptoms of high fever, headache, and muscle pain. Therefore, one must never give aspirin to a child who has flu symptoms. Also, due to the immature livers of newborns, the preservative benzyl alcohol in solutions used to flush the umbilical lines has caused death.

Prescription writing

• Inclusion of age is a legal requirement in the case of prescription-only medicines for children under 12 years of age, but it is preferable to state the age for all prescriptions for children. It is particularly important to state the strengths of capsules or tablets.
• Although liquid preparations are particularly suitable for children, they may contain sugar which encourages dental decay. Sugar-free medicines are preferred for long-term treatment. Many children are able to swallow tablets or capsules and may prefer a solid dose form; involving the child and parents in choosing the formulation is helpful.
• When a prescription for a liquid oral preparation is written and the dose ordered is smaller than 5 mL, an oral syringe will be supplied.
• Parents should be advised not to add any medicines to the infant's feed, since the drug may interact with the milk or other liquid in it; moreover, the ingested dosage may be reduced if the child does not drink all the contents.

Dosages

• Children are not mini-adults. Paediatric doses should be obtained from a paediatric dosage reference text and not extrapolated from the adult dose.
• When considering drug use in children, the following age groups should be used: Preterm (born before 37 weeks), neonate (birth to 1 month), infant (1 month to 12 months), child (1 to 12 years) and adolescent (12 to 18 years).
• Unless the age is specified, the term 'child' in the British National Formulary (BNF) includes persons aged 12 years and younger.

Dose calculation

• Children's doses may be calculated from adult doses by using age, body weight, or body surface area, or by a combination of these factors. The most reliable methods are those based on body surface area.
• Body weight may be used to calculate doses expressed in mg/kg. Young children may require a higher dose per kg than adults because of their higher metabolic rates.
• Other problems need to be considered. For example, calculation by body weight in the overweight child may result in much higher doses being administered than necessary; in such cases, dose should be calculated from an ideal weight, related to height and age (there is a simple table at the back of the Children's BNF - see under 'Further reading & references', below).
• Body-surface area estimates are more accurate for calculation of paediatric doses than body weight since many physiological phenomena correlate better to body surface area.
• Body surface area may be calculated from height and weight by means of a nomogram or using the Body Surface Area (BSA) Calculator although other paediatric drug calculators are available.[2]The Children's BNF uses the Boyd calculation here.

Safety in the home

• Patients must be warned to keep all medicines out of the reach of children. All solid dose and all oral and external liquid preparations must be dispensed in a child-resistant container unless:
• The medicine is in an original pack or patient pack such as to make this inadvisable.
• The parent will have difficulty in opening a child-resistant container.
• A specific request is made that the product shall not be dispensed in a child-resistant container.
• No suitable child-resistant container exists for a particular liquid preparation.
• All unused medicines should be returned to a supplier for destruction.