Drug Therapy in the Pediatric Patient

1
Drug Therapy in the Pediatric Patient

• Jan Bazner-Chandler
• RN, MSN, CNS, CPNP

2
Safe Drug Administration

• Administration of drugs during the first year of
  life can be a challenge due to rapid changes in
  body size, body composition, and organ function.

3
Historical Perspective

• It was not until the 1970s that the effects of
  drug on the neonate and young infant was studied.

4
Pharmacokinetics

• Absorption
• Distribution
• Hepatic metabolism
• Renal excretion

5
The Neonate birth to 4 weeks
6
Neonate - Absorption

• Two major factors affect the absorption of drugs
• pH dependent passive diffusion
• Gastric emptying

7
Gastric pH

• Gastric pH (6-8) is directly related to the
  presence of amniotic fluid in the stomach.
• Postnatally, gastric acid secretory capacity
  appears after the first 24 to 48 hours and
  gastric acidity decreases during the first weeks
  of life.
• Adult values are achieved at about 3 months of
  life.

8
Gastric pH in premature infant

• In the premature infants, gastric pH may remain
  elevated due to immature acid secretion.

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Delayed Absorption

• Prolonged emptying is seen in premature infant.
• In the neonatal period the emptying rate is
  variable and prolonged.

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Delayed absorption

• Delayed absorption may also be a result of
  diminished pancreatic enzyme function and bile
  acid secretion.

11
Absorption from skin

• Percutaneous absorption may be drastically
  increased due to immature epidermis and increased
  skin hydration.

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Absorption from muscle

• Absorption from intramuscular site may be
  unpredictable and decreased due to insufficient
  blood flow, poor muscle tone, and compromised
  muscle oxygenation.

13
Distribution

• Distribution of drugs within the body is
  influenced by the amount and character of plasma
  proteins, and relative size of fluid, fat and
  tissue compartments of the body.
• Total body water
• Plasma proteins

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Total Body Water

• 85 in pre-term infant
• 78 in neonate
• 60 at 1 year
• 64 in childhood (10 to 15 year old)
• 60 in adults
• 54 in elderly

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Metabolism

• Hepatic enzyme activity and plasma / tissue
  esterase activity are both reduced during the
  neonatal period.
• The enzyme activity increases as the infant ages
  but can be compromised in cases of severely
  malnourished infants and children.

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Metabolism

• Plasma half-life 2 to 3 times longer in neonates.

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Neonate Renal Excretion

• Renal Excretion
• At birth, glomerular function is more advanced
  that tubular function this persists until about 6
  months of age.
• This effects the efficiency at which the kidneys
  eliminate drugs.
• This is especially important in the
  administration of aminoglycosides.

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Infant 5 weeks to 1 year
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Infant - Absorption

• Low acidity in stomach until around 2 years of
  age.
• Gastric emptying still delayed.
• Percutaneous absorption continue to be increased
  through childhood.

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Absorption - IM

• Injected drugs are often erratically absorbed
  because of variability in muscle mass amount
  children and illness.
• IM generally avoided due to pain and possibility
  of tissue damage.

21
Absorption - transdermal

• May be enhanced in young children because the
  stratum corneum is thin and the ratio of surface
  area to weight is much greater than for older
  children and young adults.
• Skin disruptions (abrasions, burns, eczema)
  increase absorption.

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Absorption transrectal

• Transrectal is dependent on placement of the drug
  within the rectal cavity.
• Good for drugs such as acetaminophen (Tylenol).
• Diazepam in status Epilepticus

23
Absorption - lungs

• Varies less by physiologic parameters and more by
  reliability of the delivery device.
• Beta agonists may be used for asthma, pulmonary
  surfactant for hyaline membrane disease.

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Meds via mask
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Infant - Distribution

• Protein-binding capacity reaches adult values
  within 10 to 12 months.
• Higher doses (mg / kg) of water-soluble drugs are
  required in younger children due to higher
  percentage of their body weight in water.

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Infant Hepatic Metabolism

• Complete maturation of the liver develops by one
  year.
• Cytochrome P-450 enzyme system in the small bowel
  and liver are the most important factor in drug
  metabolism.

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Infant Renal Excretion

• Renal elimination depends on plasma protein
  binding, renal blood flow, GFR and tubular
  secretion all are altered in the first two years
  of life.

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Drug Dosing

• Dosing in children less than 12 years is always
  of function of age, body weight or both.
• When very accurate levels dosing in needed, dose
  adjustments should be based on plasma drug
  concentration.

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Child 1 to 12 years
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Pharmacokinetics

• After one year similar to adults.
• They metabolize drugs faster than adults until
  around age 2 years.
• Metabolism declines again at puberty.
• Increase in dosage or reduction in dosing
  interval may be needed for drugs that are
  eliminated by hepatic metabolism.

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Adolescent- 12 to 16 years
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Dosage Determination

• Body surface area calculations are the most
  accurate.
• Mg / kg dosing is most common calculation.

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Dosing amoxicillin

• Infants lt 3 months or neonates
• 20 30 mg / kg / day in divided doses q 12 hours

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Dosing amoxicillin

• po children gt 3 months
• 25 50 mg / kg per day in divided doses q 8
  hours
• 24 50 mg / kg per day in divided doses q 12
  hour

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Dosing amoxicillin

• Adults 250 to 500 mg q 8 hours or
• 500 to 875 q 12 hours (not to exceed 2-3 grams
  per day)

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Weight

• Remember 1 pound 2.2 kg
• If you are converting a 6 pound 5 ounce infant
  you will need to convert 5 ounces to a fraction.
  (hint 16 ounces in a pound)

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Tylenol and Motrin

• Acetaminophen can be given for infants 3 months
  of age and older

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Dosing per Davis Drug Guide

• Dosing 10 to 15 mg / kg / dose every 4 hours

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OTC Dosing

• 0-3 months 40 mg q 4 hours
• 4 to 11 months 80 mg q 4 hours
• 1-2 years 120 mg q 4 hours
• 2-3 years 160 mg q 4 hours
• 4-5 years 240 mg q 4 hours
• 6-8 years 320 mg q 4 hours
• 9-10 years 400 mg q 4 hours
• 11 years 480 mg q 4 hours
• 12-14 years 640 mg q 4 hours
• Greater than 14 years 650 mg q 4 hours

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How provided?

• Elixir
• 80 mg / 2.5 mL
• 80 mg / 5 mL
• 120 mg / 5 mL
• 160 mg / 5 mL
• Drops 80 mg / 0.8 mL
• Chewable tabs 80 mg, 160 mg
• Tablets 160 mg, 325 mg, 500 mg, 650 mg

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Ibuprofen (Advil or Motrin)

• Similar to acetaminophen in its ability to lower
  fever. FDA has approved it for infants over 6
  months of age. One advantage is a longer lasting
  effect 6 to 8 hours).

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Dosing

• Children 6 mo 12 years
• Antipyretic 5 10 mg / kg every 6 hours
• Anti-inflammatory 20 to 40 mg / kg / day in 3 to
  4 divided doses (not to exceed 50 mg / kg / day)

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How provided?

• Liquid 100 mg / 5 mL
• Oral suspension 100 mg / 5 mL
• Pediatric drops 50 mg / 1.25 mL
• Chewable tablets 50 mg, 100 mg
• Capsules 200 mg
• Tablets 100 mg, 200 mg, 300 mg, 400 mg, 600 mg,
  800 mg

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Clinical Pearl

• Never alternate Tylenol / Motrin due to dosing
  times.

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FDA Alert

• Cough and cold medications that contain
  decongestants, antihistamines, cough
  suppressants, and expectorants are commonly used
  in children to provide temporary relief of
  symptoms of upper respiratory tract infection in
  children less than 2 years of age.

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FDA Alert

• During 2004 2005 1,519 children were treated in
  ERs for adverse events
• Overdosing
• 3 deaths in infant younger than 12 months

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Cause of death

• All three infants had what appeared to be high
  levels of pseudoephedrine in postmortem blood
  samples
• One infant had a prescription and an OTC cough
  and cold medication at one time.
• Two infant had OTC cough and cold medications.

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Conclusion

• In children less than 2 years of age systematic
  reviews of controlled trials of OTC cold and
  could medications have concluded they are not
  more effective than placebo in reducing acute
  cough and other symptoms of upper respiratory
  tract infection.

49
Recommendations

• In 2006 clinical practice guidelines for
  management of cough advised health care providers
  to refrain from recommending cough suppressants
  and other OTC cough mediations for young
  children.

50
FDA

• On June 8, 2006 the FDA took enforcement action
  to stop the manufacture of carbinoxamine-containin
  g medications in children aged less than 2 years.