Chapter 10

Provide an overview of the pharmacokinetics of neonates and infants.

(Absorption, Distribution, Hepatic metabolism, Renal excretion) Pharmacokinetics: Neonates and infants -Absorption: oral, intramuscular, percutaneous -Distribution: protein binding, blood-brain barrier -Determining the concentration of a drug at its sites of action -Determining the intensity of the duration of response Elevated drug levels = more intense response Delayed elimination = prolonged response Immaturity of organs puts patient at risk for both of these responses

· Discuss factors directly related to drug distribution in neonates and infants (Endogenous compounds)

-Endogenous compounds compete with drugs for available binding sites Limited drug/protein binding in infants Reduced dosage needed Adult protein binding capacity by 10 to 12 months of age

Drug therapy in neonates & infants

-Increased sensitivity in infants Caused by immature state of five pharmacokinetic processes: -Absorption -Protein binding of drugs -Blood-brain barrier -Hepatic metabolism -Renal drug excretion

Discuss drug absorption in neonates and infants: Absorption (Transdermal absorption)

-More rapid and complete for infants than for older children and adults -Stratumcorneum of infant's skin is very thin -Bloodflow to skin greater in infants than in older patients -Infants at increased risk of toxicity from topical drugs

Important facts about pediatric patients (all pt younger than 16yrs old)

-Pediatric patients respond differently to drugs than the rest of the population -More sensitive to drugs than other patients are -Show greater individual variation -Sensitivity due mainly to organ system immaturity -Increased risk for adverse drug reactions -Ongoing growth & development

· Discuss factors directly related to drug distribution in neonates and infants (Protein binding)

-Protein binding Binding of drugs to albumin and other plasma proteins is limited in the infant Amount of serum albumin is relatively low

Discuss drug absorption in neonates and infants: Absorption (intramuscular administration)

-Slow -Erratic -Delayed absorption as a result of low blood flow during the first few days of life -During early infancy, absorption of intramuscular drugs more rapid than in neonates and adults

Main reasons a very young patient may be considered "highly" sensitive to drugs, considering both pharmacokinetic factors and pharmacodynamic factors

-Young infants have more extracellular fluid, thereby increasing their chance of becoming dehydrated (babies require larger dose of water-soluble medications to achieve therapeutic effect due to their body content being 70%) -Young infants have less body fat than adults. Therefore doses of fat-soluble meds and meds that bind to plasma proteins need to be decreased -The chances of a young infant developing neurologic toxicity is increased since the efficacy of the blood-brain barrier in infants is decreased. -Babies need a smaller dose since drugs absorb better in their stomachs (gastric acidity is low until 2 yrs old, therefore acid-labile drugs like ampicillin & penicillin is increased) -Children between the age of 1 & 12 metabolize drugs faster than adults therefore they need to increase the dosage or the dosing interval for drugs that are eliminated by hepatic metabolism (ex: drugs eliminated by the liver- need to be administered more freq.) -Absorption of IM drugs in neonates is slower than in adults. Absorption of IM drugs in infants is more rapid than in adults.

Define: Gastric emptying time

A test that measures the time it takes for food to empty from the stomach and enter the small intestine. The test often is used to find out why your child is vomiting, having stomach pain or not gaining weight.

· Discuss reasons pediatric patients are subject to adverse drug reactions when drug levels rise too high

Children are vulnerable to unique adverse effects related to organ immaturity and ongoing growth and development Age-related effects: -Growth suppression (caused by glucocorticoids) -Discoloration of developing teeth (tetracyclines) -Kernicterus (sulfonamides) -Respiratory depression (Promethazine)

Discuss dosage determination, noting that pediatric doses have been established for some drugs but not for others and, therefore, for drugs that do not have established pediatric doses, the doses can be extrapolated from adult doses.

Dosing is most commonly based on body surface area Initial pediatric dosing is, at best, an approximation Subsequent doses need to be adjusted (Body surface area of the child x adult dose) / 1.73m²

Discuss drug absorption in neonates and infants: Absorption (oral administration)

Gastricemptyingtime -Prolonged and irregular -Adult function at 6 to 8 months Gastricacidity -Very low 24 hours after birth -Doesn't reach adult values for 2 years -Low acidity: Absorption of acid-labile drugs is increased

· Discuss the pharmacokinetics of children 1 year old or older.

Important difference: Children in this age group metabolize drugs faster than adults -Markedly faster until the age of 2 years, then a gradual decline -Sharp decline at puberty -May need to increase dosage or decrease interval between doses Most pharmacokinetic parameters are similar to those of adults Drug sensitivity more like that of adults than for children younger than 1 year old

· Discuss factors directly related to drug distribution in neonates and infants (Blood-brain barrier)

Note fully developed at birth Drugs and other chemicals have relatively easy access to the central nervous system (CNS) Infants especially sensitive to drugs that affect CNS function Dosage should also be reduced for drugs used for actions outside the CNS if those drugs are capable of producing CNS toxicity as a side effect

Discuss methods that are effective at and critical to promoting parent and guardian adherence to pediatric drug regimens.

Provide patient education in writing Demonstration techniques should be included as appropriate Effective education should include the following: 1. Dosage size and timing 2. Route and technique of administration 3. Duration of treatment 4. Drug storage 5. The nature and time course of desired responses 6. The nature and time course of adverse responses

Define: adherence

Provide patient education in writing, demonstration techniques should be included as appropriate, effective education should include the following: Dosage size and timing, Route and technique of administration, Duration of treatment, Drug storage, The nature and time course of desired responses, The nature and time course of adverse responses.

· Discuss renal excretion and compare the drug-excreting capacity of a newborn with that of a 1-year-old infant.

Significantly reduced at birth Low renal blood flow, glomerular filtration, and active tubular secretion Drugs eliminated primarily by renal excretion must be given in reduced dosage and/or at longer dosing intervals Adult levels of renal function achieved by 1 year

· Discuss hepatic metabolism and compare the drug-metabolizing capacity of a newborn with that of a 1-year-old infant.

The drug-metabolizing capacity of newborns is low Neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism The liver's capacity to metabolize many drugs increases rapidly about 1 month after birth The ability to metabolize drugs at the adult level is reached a few months later Complete liver maturation occurs by 1 year of age

Define: Body surface area

drugs that do not have established pediatric dosages can be determined by adult dosages using body surface area. (child's BSA x Adult dosage)÷1.73m²

Define: Organ system immaturity

very young patients are highly sensitive to drugs Premature (36 wks gestational), Full-term (36-40 wks gestational), neonates (first 4 postnatal wks), infants (wk 5 to 52 postnatal), children (1 to 12 yrs old), adolescents (12-16 yrs old)