Pediatric Pharmacotherapy

Dr. Bereket Molla Tigabu

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Introduction
• defined as those younger than 18 years.
• Newborn infants born before 37 weeks of gestational age are termed premature;
• those between 1 day and 28 days of age are neonates;
• 29 days to 1 year are infants;
• 1 to 11 years are children; and
• 12 to 16 years are adolescents.
• Growth and development should be followed
• Growth charts are used to plot head circumference, weight, length or stature,
weight-for-length, and body mass index (BMI)

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Introduction (2)
• Gestational age (GA) Age from date of mother’s first day of last
menstrual period to date of birth
• Full term Describes infants born at 37-weeks gestation or greater
• Premature Describes infants born before 37-weeks gestation
• Small for GA Neonates with birth weight below the 10th percentile
among neonates of the same GA
• Large for GA Neonates with birth weight above the 90th percentile
among neonates of the same GA
• Chronological or postnatal age Age from birth to present, measured in
days, weeks, months, or years

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Introduction (3)
• Corrected or adjusted age: may be used to describe the age of a
premature child up to 3 years of age
• Corrected age = Chronological age in months – [(40 – GA at birth in
weeks) × 1 month ÷ 4 weeks].
• For example, if a former 29-week GA child is now 10 months old
chronologically, his corrected age is approximately 7 months: 10 months –
[(40 – 29 weeks) × 1 month ÷ 4 weeks] = 7.25 months
• LBW infant Premature infant with birth weight between 1500 and 2500
g
• VLBW infant Premature infant with birth weight 1000 g to < 1500 g
• ELBW infant Premature infant with birth weight < 1000 g

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Vital signs

Heart rate Respiratory rate

New born 100-160 New born 30-50
0-5 months 90-150 0-5 months 25-40
6-12 months 80-140 6-12 months 20-30
1-3 years 80-130 1-3 years 20-30
3-5 years 80-120 3-5 years 20-30
6-10 years 70-110 6-10 years 15-30
11-14 years 60-105 11-14 years 12-20
≥ 15 years 60-100 15-20 years 12-30
Adult 16-20

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Vital signs

Blood pressure Body temperature

Age Systolic Diastolic • The average normal core
1-12 months 75-100 50-70 temperature is generally considered
1-4 years 80-110 50-80 to be between 98.0°F (36.6°C) and
3-5 years 80-110 50-80 98.6°F (37°C) when measured
6-13 years 85-120 55-80 orally and about 1°F higher when
13-18 years 95-140 60-90 measured rectally

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 Case 1
• C.J. is a 4-month-old, 6.5 kg baby boy who has recently started teething.
His parents ask for advice on a medication to alleviate C.J.’s pain.
• What factors will influence your decision about the choice of medication
and dosing regimen for C.J.?
• What medication and dose will you recommend to his parents?

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EFFECTS OF PHARMACOKINETIC DIFFERENCES ON

DRUG THERAPY
•

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Absorption (1)
• Neonates and infants have increased gastric pH (eg, pH 6–8)
• reaching adult values by approximately 2 years of age.
• Low gastric acid secretion can result in increased serum concentrations of
weak bases and acid-labile medications, such as penicillin, and decreased
serum concentrations of weak acid medications, such as phenobarbital,
due to increased ionization.
• gastric emptying time and intestinal transit time are delayed in premature
infants, increasing drug contact time with the GI mucosa and drug
absorption

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Absorption (2)
• Pancreatic exocrine and biliary function
• are reduced in newborns, with about 50% less secretion of amylase and lipase than
adults, reaching adult values as early as the end of the first year and as late as 5
years of age.
• Deficiency in pancreatic secretions and bile salts in newborns can decrease
bioavailability of prodrug esters, such as erythromycin, which requires
solubilization or intraluminal hydrolysis
• Topical or percutaneous in neonates and infants
• absorption is increased due to a thinner stratum corneum, increased cutaneous
perfusion, and greater body surface-to-weight ratio

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 Case 2
• A.H., a 1.5-kg, 4-week-old infant girl born at 29 weeks’ gestational age, is
being treated with phenobarbital for seizures associated with a period of
asphyxia at birth. She is currently receiving a maintenance dose of 7.5 mg
(5 mg/kg) given intravenously (IV) once daily. The team wishes to
transition her to oral therapy now that she is receiving full enteral feeds. A
trough serum phenobarbital concentration obtained during IV therapy was
17.5 mcg/mL, within the desired range of 15 to 40 mcg/mL. Switching the
patient to phenobarbital elixir 7.5 mg given orally once daily results in a
serum concentration of only 8.9 mcg/mL after 1 week of therapy. What
factors might explain the lower concentration, and how should A.H. be
managed?

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 Case-3
1. C.B. is a 3.6-kg newborn boy, born at 39 weeks’ gestational age, who
was transferred to the newborn nursery after delivery. Routine care for
neonates during the first hours of life generally includes administration
of erythromycin eye ointment for prevention of neonatal ophthalmia
and 1 mg of phytonadione (vitamin K1) given intramuscularly (IM) to
prevent vitamin K-deficiency bleeding of the newborn. C.B.’s parents
question the need to give their baby a shot so soon after birth. How
would you explain the rationale for giving phytonadione IM rather than
orally?
2. C.B. is scheduled for a circumcision before discharge. The surgical site
will be prepped with a 10% povidone–iodine solution. What factors
influence the absorption of medications via this route in the neonatal
patient? Based on these factors, how should the povidone–iodine be
applied to minimize toxicity?

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Volume of distribution
• Extracellular fluid and total body water per kilogram of body weight are
increased in neonates and infants, resulting in higher Vd for water-soluble
drugs, such as aminoglycosides, and decreases with age.
• Neonates and infants have a lower normal range for serum albumin (2–4
g/dL, 20–40 g/L), reaching adult levels after 1 year of age.
• Highly protein–bound drugs, such as sulfamethoxazole-trimethoprim and
ceftriaxone, are not typically used in neonates due to theoretical concern
for bilirubin displacement.
• This displacement may result in a complication known as kernicterus, from
bilirubin encephalopathy

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Metabolism (1)
• Phase 1 reactions and enzymes, such as oxidation and alcohol
dehydrogenase, are impaired in premature neonates and infants and do not
fully develop until later childhood or adolescence.
use of products containing ethanol or propylene glycol can result in increased
toxicities
• Increased dose requirements by body weight (eg, mg/kg) for some
hepatically metabolized medications (eg, phenytoin, valproic acid) in
young children (ie, ages 2–4 years of age) are theorized due to an
increased liver mass to body mass ratio
• Glucuronidation by the uridine diphosphate glucuronosyltransferases, in
contrast, is immature in neonates and infants, reaching adult values at 2 to
4 years of age

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Metabolism (2)
• Products containing benzyl alcohol or benzoic acid should be avoided in
neonates due to immature glycine conjugation, resulting in accumulation
of benzoic acid.

• This accumulation can lead to “gasping syndrome,” which includes respiratory

depression, metabolic acidosis, hypotension, seizures or convulsions, and gasping
respirations

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Elimination
•

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Case-4
• JJ is a 3-week-old (weight 4 kg, length • JJ’s Laboratory Values
55 cm, no known drug or food • WBC 19 × 103 /mm3 (RR:6–17.5 ×
allergies), full-term male who presents 103 /mm3)
to the emergency department with
lethargy, poor oral intake, and fever. JJ • Bands 8% (RR:4–12%)
is admitted to the general pediatric • Segs 38% (RR:13–33%)
ward for further assessment including • Lymphs 60% (RR:41–71%)
a neonatal sepsis and meningitis rule
out. Blood samples, cerebral spinal • Monocytes 5% (RR: 4–7%)
fluid, and urine were collected for • SCr 0.3 mg/dL (RR:≤ 0.6 mg/dL)
Gram stain and culture, still pending
• The medical resident asks you
results. Given his poor oral intake on
whether ceftriaxone (highly protein
admission, the team requests the
binding) or cefotaxime (low protein
consultation regarding antibiotic
binding) should be used why?
selection.

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Pharmacodynamic (efficacy and

toxicity)
• Clinical presentation of chronic asthma differs in children and adults
• Children present almost exclusively with a reversible extrinsic type of asthma
adjunctive hyposensitization therapy
• The maintenance dose of digoxin is substantially higher in infants than in
adults.
• a lower binding affinity of receptors in the myocardium for digoxin and
• increased digoxin-binding sites on neonatal erythrocytes compared with adult
erythrocytes
• Insulin requirements are highest during adolescence because of the
individual’s rapid growth

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 Case 5
• S.L. is a 0.725-kg infant boy with an estimated gestational age of 24
weeks. He was brought to the neonatal intensive care unit immediately
after birth with severe hypotension. A dopamine infusion was started at a
rate of 10 mcg/kg/minute and quickly titrated to 20 mcg/kg/minute
without significant benefit. What might explain S.L.’s lack of response,
and how should his hypotension be managed?

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Toxicity (1)
• Promethazine now is contraindicated for use in children younger than 2
years because of the risk of severe respiratory depression.
• Chloramphenicol toxicity is increased in newborns because of immature
metabolism and enhanced bioavailability.
• propylene glycol can cause hyperosmolality in infants
• Benzyl alcohol cause a syndrome of metabolic acidosis, seizures,
neurologic deterioration, gasping respirations, hepatic and renal
abnormalities, cardiovascular collapse, and death in premature infants

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Toxicity (2)
• antihistamines, decongestants, antitussives, and expectorants not be used
in children younger than 2 years of age
• Tetracyclines are contraindicated for use in pregnant women, nursing
mothers, and children younger than 8 years because these drugs can cause
dental staining and defects in enamelization of deciduous and permanent
teeth, as well as a decrease in bone growth

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Specific considerations in drug

therapy
i. Off-Label Medication Use ii. Common Errors in Pediatric
• more than 75% of drugs approved in Drug Therapy
adults
iii. Medication dose calculation
• It is appropriate to use a drug off-label error
when no alternatives are available;
• should refer to published studies and iv. CAM and OTC medications
case reports for available safety, v. Medication administration
efficacy, and dosing information

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