Children as Patients General Overview

Children as Patients General Overview. In this section we will explore various considerations important to treating children. Topics covered will include pharmacokinetic differences in children, developmental aspects of pediatric prescribing, and factors that influence positive outcomes. There are several important historical events related to children and medications. Getting a medication approved for children is a much more involved process than that required for adults.

Developmental Pharmacology

Developmental changes can affect drug absorption, binding, renal elimination, and metabolism. For instance, gastric pH does not reach adult values until a child is 20-30 months old. Oral availability of acid labile compounds such as beta-lactams is increased. Oral bioavailability of weak organic acids such as phenobarbital and phenytoin are decreased. Basic drugs like diazepam and theophylline have an increased absorption. Most orally administered medications are absorbed in the small intestine. While infants have a proportionally larger small intestinal surface area, they have unpredictable absorption compared to adults. This is partly due to their increased intestinal motility. Due to limited water solubility of drugs like phenytoin and carbamazepine, drug absorption is altered.

Distribution of medications once absorbed is also impacted by newborns and infants having a higher percentage of water in their system. In newborns, the blood-brain barrier is incomplete and still permeable so some medications that cross the blood-brain barrier must be evaluated closely. Infants under 6 months of age have decreased plasma proteins available for drug binding. As children enter into adolescents their total body fat decreases. Lean body mass increases in males as fat distribution decreases. However, fat distribution in females increase to prepare the reproductive system for child rearing as fat is an important component of female hormone regulation. For these reasons, it can be difficult to predict pharmacokinetics of some drugs during adolescence.

Drugs are metabolized by both metabolic and enzymatic reactions. There are Phase I and Phase II enzymes and enzymes mature at varying rates.

Transcript

Phase I Enzymes

CYP P450

  • Family of drug-metabolizing enzymes
  • Account for majority of drug metabolism in humans
  • The enzymes may be slowed (inhibited) or increased (induced).
  • Concurrent therapy with an inhibitor or inducer may alter the metabolism of a medication.

CYP 1A2

  • Developmental variation
    • Reaches adult levels at 4 months
    • Exceeds adult levels at 1 to 2 years
    • Reaches adult levels at puberty
  • Diseases such as cystic fibrosis (CF) can affect CYP 1A2 activity.
  • Medications: many
    • Theophylline, erythromycin, cimetadine, phenobarbitol, phenytion, carbamazepine, clarithromycin, etc.
  • Food
    • Grapefruit juice, cruciferous vegetables, charbroiled foods
  • Cigarette smoking

CYP 3A4

  • Developmental variation
    • Low activity at birth
    • 30% to 40% of adult level by age 1 month
    • Full adult level at age 6 months
    • Exceeds adult level at 1 to 4 years of age
    • Decreases to adult level after puberty
  • Used to metabolize more than 20 commonly used pediatric medications
    • Carbamezapine, prednisone, oral contraceptives, macrolides, NSAIDs, antihistamines, etc.
  • Implications for practice
    • Monitor when on more than one drug metabolized by CYP 3A4 enzyme.
    • Monitor during developmental changes.

Phase II enzymes are responsible for synthesis of water-soluble compounds. Most reach adult activity by age three to four. There is less information available on Phase II activity in children but some ethnic variations are known. Koreans do not reach adult activity levels of thiopurine methyltransferase (TPMT) until 7 to 9 years. Common medications impacted by Phase II enzymes include acetaminophen, morphine, propofol, and caffeine. Implications for practice related to Phase II enzymes include the need to monitor therapeutic effectiveness based on developmental age and the need to understand ethnic variations in metabolism may be present. Patients with low levels of TPMT activity are at greater risk of hepatic toxicity from some chemotherapy drugs (thiopurines). Patients with low or undetectable levels of TPMT activity experience severe myelosuppression when treated with standard doses of thiopurines. Additionally, patients with high levels of TPMT activity are likely to have reduced clinical responses.

Elimination

Renal blood flow and glomerular filtration rate reaches adult levels at 9 months of age. Medications should be adjusted to account for decreased renal function in children under 9 months of age. Medications can also be excreted in breast milk so children who are being breastfed will need to have maternal medication consumption considered as well. Factors that influence infant exposure to maternal drugs include:

  • Maternal phenylketonuria
  • Time of feeding in relation to dosing
  • Infant phenylketonuria
  • Susceptibility to drugs effects
  • Milk to plasma ration (M:P)

 

Transcript

Pediatric Medication Administration

  • Infants
    • Teach parents about medications.
    • Teach how to administer medications.
  • Toddlers and preschoolers
    • Independence
    • Use higher concentrations so lower volume.
  • School-age children
    • Industrious
    • Liquid vs. pills

Adolescence

When treating adolescents there are important considerations from a social development perspective. While adolescents are busy finding and exerting their independence, they are also highly interdependent. Many teenagers are interdependent on peers but this should not be assumed and each patient should be assessed to determine the providers best approach as it relates to developmental stage. Practitioners should also be aware of their state laws regarding consent to treat adolescence without the presence of a guardian and when this is acceptable. There are also unique confidentiality laws regarding adolescence when an adolescent seeks care or consultation for reproductive or sexual health concerns.

There are several factors the influence positive medication treatment outcomes. These include:

  • Length of treatment
  • Complexity of regimen
  • Medication interval
  • Palatability
  • Cost
  • Family issues

Strategies to improve medication adherence include adjust the concentration of medications to decrease the number of dosages needed in a 24-hour period if possible. Written and oral instructions may also be helpful. For busy families, the use of calendars to either note reminders of when medication should be administered or using a sticker chart for rewarding children for taking their prescribed medications. Depending on the severity of the condition and family needs, telephone reminders can also be set up. A more serious and extreme possibility is the use of contracts. Contracts are sometimes used when there is a legal outcome to either patients and families not taking medications as prescribed or there is some question of who is consuming the prescribed medication.

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Children as Patients General Overview

Children as Patients General Overview

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