Pediatric Pharmacology

Question 1

The fat and water percentage in an infant relative to an adult

The effect on Vd

Answer 1

• Infants have a higher percentage of body fat AND total body water
• Therefore, the Vd for both fat- and water-soluble drugs is HIGHER compared to adults

Question 2

What biotransformation do Morphine, NSAIDs, APAP, and endogenous compounds such as bilirubin proceed through?

How does this relate to children?

Answer 2

glucuronidation

It is poorly developed early on in fetal and neonatal life

Question 3

What limits drug elimination in the newborn period?

How low may GFR be in comparison to adults?

Answer 3

In the newborn period, immaturity of the kidney limits glomerular and tubular functional
capacity, resulting in decreased drug elimination and prolonged half-lives.

Neonatal glomerular filtration rate (GFR) may be as low as 5%-10% of the value in adults. This
aspect is important in avoiding toxicity in the neonatal population.

Question 4

How does Vd differ from patient to patient?

What is it mostly due to?

Answer 4

Based on protein binding and body compositon that has significant age-related differences.

Mostly due to alteration in total body water.

Question 5

To achieve comparable concentration of drugs that distribute in total body water, what must be given to infants and children?

Why?

Answer 5

Higher doses per kg body weight must be given to infants and children.

The total body water is greater in neonates and infants than in adults

Question 6

Age Glomerular Filtration Rate

First year of life

Answer 6

Age Glomerular Filtration Rate

Premature 5-10 ml/min/m2

Term neonate (40 weeks gestation) 10-15 ml/min/m2

42-45 weeks 20-30 ml/min/m2

6-12 months old 70-75 ml/min/m2

Question 7

Cutaneous Absorption:

In infancy

In premature infants

Answer 7

Enhanced during infancy: due to development of cutaneous layers (not fully developed and thinner), level of hydration and cutaneous perfusion of the epidermis in children

Children/infants also have a higher proportion of body surface area to mass

Premature infants: enhanced cutaneous absorption may be even greater due to the fact that barrier dysfunction has a linear relationship with prematurity (ie. more premature an infant it is, the less fully developed the barrier function of the integument)

Question 8

Intramuscular Absorption:

Answer 8

Intramuscular Absorption:

Not a preferred route in pediatrics: due to pain (but a good alternative in patients with poor IV access)

Question 9

Gastric PH in infants

Results

Answer 9

Changes in gastric pH (higher in neonates than adults- neutral at the time of birth and then has a delayed drop over several months)

pH of 4-7 for first few weeks of life; pH of 3 by 4 months of age

Result:
Acid-labile medications will be readily absorbed (ie. penicillin G)
Weak acids may need LARGER oral doses in neonates to reach therapeutic levels (ie. phenobarbital)

Question 10

Solution vs. Suspension

Answer 10

Solution: medication dissolved throughout the liquid

Suspension: medication particles suspended in the liquid and are subject to gravity (will sink to the bottom; need to SHAKE BEFORE USE*)

Ingesting a suspension (which has a larger surface area:volume ratio) can result in a more rapid transmucosal transport and a shorter lag to peak serum concentration compared to a tablet

Question 11

Protein binding in infants compared to adults

Answer 11

DECREASED protein binding

Drugs that are highly protein bound (ie. phenytoin) will therefore have their free (and active) concentrations increased

Therapeutic drug monitoring of serum levels of bound and unbound drug is important

Question 12

How does the fat and water composition of an infant affect Vd?

Answer 12

Infants have a higher percentage of body fat AND total body water

Therefore, the Vd for both fat- and water-soluble drugs is HIGHER compared to adults

Question 13

What is an example of a disease based off of ineffective clearance of a drug?

Answer 13

gray-baby syndrome with chloramphenicol

Question 14

Drugs metabolized in the liver show:

Fetal and neonatal metabolism

Plasma clearance

Answer 14

Drugs metabolized in the liver show:

A DECREASE in fetal and neonatal metabolism

An age-dependent INCREASE in plasma clearance in children younger than 10 as compared to adults (more efficient clearance in childhood)

Question 15

What is an example of a drug metabolism that can be higher in infants and children than in adults?

Answer 15

Example: carbamazepine (clearance is higher in children resulting in higher dose per body weight and shorter interval between doses for children)

Question 16

What are 3 drugs that can cause adverse events in children in in the presence of appropriate dosing?

Answer 16

Tetracyclines: contraindicated in kids under 8 due to teeth discoloration

Fluoroquinolones: can cause tendon problems in young animal models and has been implicated in poor cartilage development (use is limited in pediatrics- only used if no reasonable alternative exists)

Ceftriaxone: can displace bilirubin from albumin in premature infants and neonates with hyperbilirubinemia, potentially causing kernicterus (rarely used in neonates due to other alternatives)

Question 17

DA Agonists in children:

DA-R in children vs. adults

Metoclopromide

DA in critical care

Answer 17

Medications with DA Agonist Effects:

Children have a greater propensity for dystonic reactions (pediatric brain has a higher proportion of DA-2 receptors)

Metoclopromide: given as propulsive agent for children with GERD, but also has DA agonism

DA infusions also used to critical care for catecholamine response in shock (effects on heart and vasculature may help reverse shock state)

Neonates have relatively immature catecholamine receptor density and function

Respond poorly to doses that increase HR and BP in older children and adults

Question 18

Agents producing mild CNS depression:

Examples:

Effects in children:

Answer 18

Agents producing mild CNS depression:

Examples: antihistamines, low dose benzos, barbiturates

Effect in Children: may show paradoxical hyperexcitability following administration (these drugs normally result in sedation in adults)