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Pharmacology and Pediatrics
Age Groups of Pediatrics Population
Group                  Age
Preterm or premature   Less than 36 weeks gestational age
Neonate                Less than 30 days of age
Infant                 1 month until 1 year of age
Child                  1 year until 12 years of age
Adolescent             12 years of age until 18 years of age
Oral Drug Absorption in the Neonate vs Older
            Children and Adults

              Drug       Oral Absorption
 Acetaminophen       Decreased
 Ampicillin          Increased
 Diazepam            Normal
 Digoxin             Normal
 Penicillin G        Increased
 Phenobarbital       Decreased
 Phenytoin           Decreased
 Sulfonamides        Normal
AGE-RELATED PHARMACOKINETIC
DIFFERENCES IN CHILDREN COMPARED
WITH ADULTS
Premature Neonate   Neonate          Infant      Child             Adolescent

                                                      Absorption

Gastric acidity         Decreased           Decreased        Decreased   Equal             Equal

Gastric emptying time   Decreased           Decreased        Equal       Equal             Equal

GI motility             Decreased           Decreased        Decreased   Equal             Equal

Pancreatic enzyme       Significantly       Decreased        Decreased   Equal             Equal
activity                decreased
GI surface area         Increased           Increased        Increased   Increased         Equal

Skin permeability       Significantly       Increased        Equal       Equal             Equal
                        increased
                                                      Distribution

Body composition                                                                           Equal

Blood-brain barrier     Decreased           Decreased        Equal       Equal             Equal

Plasma proteins         Significantly       Decreased        Equal       Equal             Equal
                        decreased
                                                      Metabolism

Liver                   Decreased           Decreased        Decreased   Equal/Increased   Equal

                                                      Elimination

Renal blood flow        Decreased           Decreased        Decreased   Equal             Equal

Glomerular filtration   Decreased           Decreased        Decreased   Equal             Equal

Tubular function        Decreased           Decreased        Decreased   Equal             Equal
Drug Distribution
• Drug distribution in the neonate depends on
  – Amount of body water, body fat and drug binding
• Body water (BW)
  – Neonates have more BW than adults (70% vs 50%)
  – Full-term: 70% body weight is water
  – Pre-term: 85% body weight is water
• Body fat
  – Pre-term infants have much less fat than full-term
  – Lipid soluble drugs may not be accumulated
• Drug binding to plasma proteins
  – Binding of drugs to albumin is reduced
  – Drug competition for binding albumin may occur
Drug Excretion
• GFR is much lower in newborns than in older
  infants, children or adults
• This limitation persists during the first days of
  life and improves thereafter
• Neonatal GFR based on body surface area
  –   Birth: Only 30-40% of the adult value
  –   3 weeks: 50-60% of the adult value
  –   6-12 months: Reaches adult values
  –   Thus, renal elimination occurs is very slow initially
• Toddlers
  – Have shorter drug elimination (t½) than older
    children and adults probably due to ↑ renal
    elimination and metabolism
Pediatric Dosage Forms
• Elixir
   – Alcoholic solutions in which the drug molecules are
     dissolved and evenly distributed
   – No shaking is required
   – Generally, all doses contain equivalent amounts
• Suspension
   – Contains undissolved drug particles that must be
     distributed throughout the vehicle by shaking
   – Caution: Risk of administering unequivalent doses
     may lead to toxicity or lack of efficacy

• Prescriber awareness and care giver education
  on these differences is important
Compliance
• Compliance may be difficult to achieve since it
  involves many factors
  – Parent’s ability to follow directions
  – Measuring errors
  – Spilling and spitting out
• Recommendations to improve compliance
  –   Pill boxes
  –   Calibrated medicine spoon
  –   Ask if parent gives another dose after spitting out
  –   Stress importance of duration of treatment
  –   Instruct whether to wake the child during q6h dosing
  –   Give some responsibility to the child for his/her care
Pediatric Drug Dosage
• Most drugs approved for use in children have
  pediatric doses, stated in mg/kg
• If recommendations are not available, an
  approximation can be made by any of several
  methods
• Methods include : Age, weight, or surface area
  –   Age: Young’s rule
  –   Weight: Clark’s rule
  –   Doses based on age or weight are conservative
  –   Doses based on surface area are more adequate
• The calculated pediatric dose should never
  exceed the adult dose!
Clark’s Rule
• Formula for Clark's Rule is:
  Weight of the child in pounds/150 ("normal" adult
  weight) X the usual adult dose
• The adult dose of a medication is 30 mg. The child's
  weight is 30 lbs. What is the correct dose?
  30/150 = 1/5
  1/5 x 30 mg = 6 mg
• Preferred method
Young’s Rule
• Pediatric doses for children over the age of 2
  based on the adult dose. Not as precise as
  Clark’s rule.

  Take the age of the child in years and divide that
  by their age plus 12.
• Multiply this number times the adult dose.

  Pediatric dose = [age/(age + 12)] x adult dose

• 2/14 X 250mg = 35 mg for a child age 2 yrs

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Pediatrics pharmacology

  • 2. Age Groups of Pediatrics Population Group Age Preterm or premature Less than 36 weeks gestational age Neonate Less than 30 days of age Infant 1 month until 1 year of age Child 1 year until 12 years of age Adolescent 12 years of age until 18 years of age
  • 3. Oral Drug Absorption in the Neonate vs Older Children and Adults Drug Oral Absorption Acetaminophen Decreased Ampicillin Increased Diazepam Normal Digoxin Normal Penicillin G Increased Phenobarbital Decreased Phenytoin Decreased Sulfonamides Normal
  • 4. AGE-RELATED PHARMACOKINETIC DIFFERENCES IN CHILDREN COMPARED WITH ADULTS
  • 5. Premature Neonate Neonate Infant Child Adolescent Absorption Gastric acidity Decreased Decreased Decreased Equal Equal Gastric emptying time Decreased Decreased Equal Equal Equal GI motility Decreased Decreased Decreased Equal Equal Pancreatic enzyme Significantly Decreased Decreased Equal Equal activity decreased GI surface area Increased Increased Increased Increased Equal Skin permeability Significantly Increased Equal Equal Equal increased Distribution Body composition Equal Blood-brain barrier Decreased Decreased Equal Equal Equal Plasma proteins Significantly Decreased Equal Equal Equal decreased Metabolism Liver Decreased Decreased Decreased Equal/Increased Equal Elimination Renal blood flow Decreased Decreased Decreased Equal Equal Glomerular filtration Decreased Decreased Decreased Equal Equal Tubular function Decreased Decreased Decreased Equal Equal
  • 6. Drug Distribution • Drug distribution in the neonate depends on – Amount of body water, body fat and drug binding • Body water (BW) – Neonates have more BW than adults (70% vs 50%) – Full-term: 70% body weight is water – Pre-term: 85% body weight is water • Body fat – Pre-term infants have much less fat than full-term – Lipid soluble drugs may not be accumulated • Drug binding to plasma proteins – Binding of drugs to albumin is reduced – Drug competition for binding albumin may occur
  • 7. Drug Excretion • GFR is much lower in newborns than in older infants, children or adults • This limitation persists during the first days of life and improves thereafter • Neonatal GFR based on body surface area – Birth: Only 30-40% of the adult value – 3 weeks: 50-60% of the adult value – 6-12 months: Reaches adult values – Thus, renal elimination occurs is very slow initially • Toddlers – Have shorter drug elimination (t½) than older children and adults probably due to ↑ renal elimination and metabolism
  • 8. Pediatric Dosage Forms • Elixir – Alcoholic solutions in which the drug molecules are dissolved and evenly distributed – No shaking is required – Generally, all doses contain equivalent amounts • Suspension – Contains undissolved drug particles that must be distributed throughout the vehicle by shaking – Caution: Risk of administering unequivalent doses may lead to toxicity or lack of efficacy • Prescriber awareness and care giver education on these differences is important
  • 9. Compliance • Compliance may be difficult to achieve since it involves many factors – Parent’s ability to follow directions – Measuring errors – Spilling and spitting out • Recommendations to improve compliance – Pill boxes – Calibrated medicine spoon – Ask if parent gives another dose after spitting out – Stress importance of duration of treatment – Instruct whether to wake the child during q6h dosing – Give some responsibility to the child for his/her care
  • 10. Pediatric Drug Dosage • Most drugs approved for use in children have pediatric doses, stated in mg/kg • If recommendations are not available, an approximation can be made by any of several methods • Methods include : Age, weight, or surface area – Age: Young’s rule – Weight: Clark’s rule – Doses based on age or weight are conservative – Doses based on surface area are more adequate • The calculated pediatric dose should never exceed the adult dose!
  • 11. Clark’s Rule • Formula for Clark's Rule is: Weight of the child in pounds/150 ("normal" adult weight) X the usual adult dose • The adult dose of a medication is 30 mg. The child's weight is 30 lbs. What is the correct dose? 30/150 = 1/5 1/5 x 30 mg = 6 mg • Preferred method
  • 12. Young’s Rule • Pediatric doses for children over the age of 2 based on the adult dose. Not as precise as Clark’s rule. Take the age of the child in years and divide that by their age plus 12. • Multiply this number times the adult dose. Pediatric dose = [age/(age + 12)] x adult dose • 2/14 X 250mg = 35 mg for a child age 2 yrs