pediatric pharmacology UoD-college of medcine Kurdistan

1. Principles of
Neonatal &
Pediatric
Pharmacology
Prepared by Zerin Sabah, Dunya Ahmed, Sliva Moayad,
Aydin Ibrahim, Jarin Sagvan
Supervised by Dr. Hishyar and Dr. Hussein

2. • Background
• Pediatric Ages
Introduction
• Absorbtion
• Distribution
• Metabolism
• Excretion
Peidatric Pharmacokinetics
• Vital signs
• Biochemical parameters
Monitoring Paramters
• Pediatric drug Therapy
• Dose Calculation
• Adverse Reaction
Peidatric Dosage

3. Introduction

4. Introduction
 Pharmacokinetics and Pharmacodynamics data are seldom avaible
o have not undergone specific pre-marketing clinical studies in children
 Data on therapheutic dosing for children
o based on case reports or very small population studies
o observations of usually unscientific observers
 Surface area, weight and age are common methods currently avaible to
predict paediatric therapheutic doses from those used for adults
 Special challenge
o constantly changing physiological and developmental status

5. Introduction
Normal length 37 - 42 weeks
Preterm <37 weeks gestational age
Post-term >42 weeks gestational age
Neonatal period Up to 28th day
Infant 1-12 months
Toddler 1-4 years
Children 4-12 years
Adolescent 12-18 years

6. Pharmacokinetics

7. Drug Absorption
Routes of Drug Absorption
1. Oral route
o pH dependent passive diffusion
o Gastric emptying time
o Peristaltic movement
o GI enzyme activitys
o Disease state
 In neonate irregular in any newborn baby and unavailable in the ill baby
 In older infants and children orally administered drug will be absorbed
at a rate and extent similar to those in healthy adults
Routes of
Drug Delivery
Oral
IM
IV
Topical
Rectal
Buccal

8. Drug Absorption
2. Intramuscular route
o avoided in premature babies because of their small muscle bulk.
o In infants and children the absorption is faster than in the neonatal period since
the muscle blood flow is increased
3. Topical route
o Premature infants have underdeveloped epidermal barrier (stratum corneum)
 Lead to poor barrier to water and highly permeability to substances
o Infants have increase in permeability of skin
 this will increase topical drug absorption

9. Drug Absorption
4. Intravenous route
o Absorption is complete 100% (maximum bioavailability)
5. Rectal Route
o Useful in patients who are vomitting or unable to take oral medication
o Rectal absorption probably similar to upper GIT
 But different PH, surface area and fluid content
6. Buccal Route
o Useful in patients who are vomitting or unable to take oral medication
o In neonate adminstration of glucose gel in treatment of hypoglycaemia

10. Drug Distribution - Review
 Reversible transport of drug by bloodstream to ist site of action
 Compartments for Distribution:
o Intracellular 40% Extracellular (Plasma 4%, Interstitial fluid 15%, Transcellular fluid 1%)
 Factors affect Distribution
o Blood flow, Permeability, Transport mechanism, Plasma proteins
 Volume of Distribution
o Vd = D/C -> C = D/Vd, as smaller Vd as larger the concentration
 Compartment Models
 Redistribution

11. Drug Distribution
80
70
61.2 64.8 64.4 60
54
12
13.4
13.4
17.3 18.1
16.5
12
6
13.4
22.4
13.7 13
18
30
2 3.2 3 4.2 4.3 5.5 4
0
10
20
30
40
50
60
70
80
90
100
Premature Full term 1 year 10 years 15 years Adult Eldery
Body Composition
Water Protein Fat Mineral

12. Drug Distribution
 The volume of distribution of drugs changes in children due to changes in body
composition and plasma protein binding through growth and development
1. Body water
o In younger children higher percentage of body weight is water
 Higher doses of water-soluble drugs are required in younger children
 Lower doses are required to avoid toxicity as children grow older
2. Body fat
o Amount of adipose tissue vary in different babys
 In general neonate, especially pre term, have less fat
 Lipid soluble drugs are not accumulated at fat reservoir
 Faster half-life elimination

13. Body Distribution
3. Plasma proteins
o Protein binding is lower because
1. Albumin and total protein concentrations are lower in neonates until 1 year
2. qualitative differences in binding proteins
3. competitive binding by molecules such as bilirubin and free fatty acids,
which circulate in higher concentrations in neonates and infants
 result may be
1. increased free drug concentrations
2. greater drug availability at receptor sites
3. Higher pharmacologic effects and adverse effects at lower drug concentrations

14. Drug Metabolism - Review
 Location
o Occurs primarily in the liver
o additional biotransformation occurs in the intestine, lung, kidney, adrenal gland and skin
 In liver, metabolism involves:
o Phase I reactions (Non Synthetic reactions)
o Phase II reactions ( Synthetic reactions)
 Phase I reactions
o Oxidation, reduction, hydrolysis
o Cytochrome family enzymes
 Phase II reactions
o Glucuronidation, sulfation, acetylation, glutathione conjugation

15. Drug Metabolism
 Depends greatly on the maturation level of the pediatrics patient and varies
from child to child.
 For most children younger than 2 years:
o Sustained decrease in levels of hepatic enzymes result in slower metabolism of
medications.
o Hepatic metabolic activity is lower in neonates, infant hepatic function matures at
age 1 to 2 months.
 Pediatric patients generally have higher metabolic rates than adults.
o Which courses the metabolism of medications to occur more rapidly
o Often necessitates a higher medication requirement than with adults

16. Drug Excretion - Review
 occurs in the kidneys, liver, intestine, lungs,
sweat, salivary and mammary glands
 Kidney is the major route of elimination for
o water soluble drugs
o water soluble metabolites of lipid soluble drugs
 The basic processes in renal elimination
1) Glomerular filtration
2) Tubular function

17. Drug Excretion
1) Glomerular filtration
o Premature infants have reduced filtration rates due to incomplete nephrogenesis
• 30% - 50% of adult value in full term neonates
• 85% adult values by 3-5 months of age
• 100% adult values by 6-12 months of age
2) Tubular function
o In infants tubular secretion rates are approximately 20%
o Does not achieve adult values until 6-7 months of age
o In neonates tubular reabsorption is decreased

18. Absorption
Distribution
Metabolism
Elimination

19. Monitoring parameters

20. Monitoring parameters
 It give an idea about therapy management in prolonged treatment
 Pediatric vital signs, Biochemical and Hematology parameters change
through childhood
Vital Signs
PARAMETERS AGE 2-5 AGE 5-12
Heart rate (beats/min) 100-120 80-100
Systolic blood pressure (mmHg) 80-90 90-110
Respiratory rates (beats/min) 25-30 16-25

21. Monitoring parameters
Biochemical and Hematologic Parameter
PARAMETERS AGE 2-5 AGE 5-12
Albumin (g/L) 30-50 35-55
Bilurubin (microM/L) <15 <17
Creatinine (microM/L) 30-80 50-120
Hemoglobin (g/dL) 11-14 Male: 13.5-18
Female: 12-16
WBC (x 109
/L ) 5-14 3.5-11

22. Pediatric Drug Therapy

23. Pediatric Drug Therapy
 a general term for using medication to treat disease
1. Dose Calculation
o Depends on age, weight and surface area
2. Choice of Dosage form
o Depends on choice of route of absorption
3. Disease Condition
o Liver, Kidney and Lung disease
4. Adverse Reaction
o Not cleared, but some well known
5. Counseling
o Concordence and adherence of both parents

24. Dose Calculation
 Clarks Rule
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑐ℎ𝑖𝑙𝑑 (𝑖𝑛 𝑝𝑜𝑢𝑛𝑑𝑠)
𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑎𝑑𝑢𝑙𝑡 𝑤𝑒𝑖𝑔ℎ𝑡 (150 𝐼𝑏𝑠)
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
 Frieds Rule
𝑎𝑔𝑒 (𝑖𝑛 𝑚𝑜𝑛𝑡ℎ)
𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑎𝑑𝑢𝑙𝑡 𝑤𝑒𝑖𝑔ℎ𝑡 (150 𝐼𝑏𝑠)
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
 Youngs Rule
𝑎𝑔𝑒 (𝑖𝑛 𝑦𝑒𝑎𝑟𝑠)
𝑎𝑔𝑒+12
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒
 Catzel Rule
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒𝑎 𝑜𝑓 𝑐ℎ𝑖𝑙𝑑 (𝑖𝑛 𝑚2)
𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑎𝑑𝑢𝑙𝑡 𝑠𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒 (1.76𝑚 2)
× 𝑡ℎ𝑒 𝑢𝑠𝑢𝑎𝑙 𝑎𝑑𝑢𝑙𝑡 𝑑𝑜𝑠𝑒

25. Adverse Reaction
 Mechanism is not cleared in adverse effect of many drugs in child#
o may be due to immature kinetic parameters and some medication errors
 Some well known adverse effect
•Teeth brown coloration
Tetracycline
•Growth suppression in Prepubertal
childCorticosteroids
•Paradoxical hyperactivity in child
Phenobarbital drugs
• Reye’s syndrom
Aspirin

26. Resources
 Websites
o https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341411/
o https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857037/
o http://www.merckmanuals.com/professional/pediatrics/principles-of-drug-treatment-in-
children/pharmacokinetics-in-children
 Videos
o https://www.youtube.com/watch?v=fM1J6rYCx38
o https://www.youtube.com/watch?v=kXQzyook0v8
o https://www.youtube.com/watch?v=Q2CX36XhMj0
 Books
o Sumner J. Yaffe Neonatal and Pediatric Pharmacology:
Therapeutic Principles in Practice 2010
o Roker Walker and Cate Whittlesea Clinical Pharmacy and Therapheutics:
Fifth Edition 2012
 Other
o Dr Hisyhar Lectures on Pharmacokinetics 2017