oleh

Muhammad Amir Ihsan B. Mohd Aminuddin

KK Manong , PKD Kuala Kangsar

 Introduction
Pharmacokinetic of Children

A, D, M, E

Drug Therapy in Children

Contents

Dose Calculation

Appropriate Dosage form and route

Counseling

Summary
References

Introduction
Pediatric means..

Age:- 12-16
years
(Adolescents)

1 month 1year
(Infants)

Day 1 1Month
(Neonate)

1- 11 years
(Children)

Importance of drug handling:

Pediatric Pharmacology -Whats unique?
 Descriptive pharmacology (especially for new drugs) in
pediatric patients is often lacking
 Animal studies not always predictive.
 Clinical studies in children fraught with ethical and
financial hurdles.
 Administration of drug can also be problematic.
 Extremely small margin of error for the most fragile
patients
o Errors can be devastating
o Individual variance unpredictable
 Highly Critical aspects in child treatment are
 Pharmacokinetic parameters
 Method of drug administration
 Dose & dosage forms
4

The Normal Child:

Growth and development are important indicators of a
childs general well-being and pediatric practitioners
should be aware of the normal development milestones
in childhood.
The World Health Organization (WHO) has published
the widely used growth charts.
Three important tools in developmental assessment.
Height
Weight
Head circumference

Pharmacokinetics:
There is high importance of clinical pharmacokinetics
in optimization of drug therapy.
Drugs that are safe and effective in one group of
pediatric patients may be ineffective or toxic in
another, so an understanding of variability in drug
disposition is essential if children are to receive
rational and appropriate drug therapy.

DISTRIBUTION

EXCRETION

ABSORBTION

METABOLISM

E
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Absorption from GI tract

Two factors affecting the absorption of drugs
from the G.I. tract are pH-dependent passive
diffusion and gastric emptying time.

PH

Premature Infants- Elevated pH (More

alkaline) higher serum concentrations of acidlabile drugssuch as penicillin and ampicillin

Infant- Range from 6-8

Gastric
Emptying

Infants/Neonate:Prolonged
gastric
emptying time. Drug limited absorption in
adults may be absorbed efficiently in a
premature infant because of prolonged
contact time with GI mucosa.
8

Absorption from Intramuscular route: less predictable absorption in infant

Factors:
Less Muscle mass
Poor perfusion in Muscle
Insufficient muscular contractions

Absorption from Skin : Percutaneous absorption may be increased in

neonate because of an underdeveloped epidermal
barrier (stratum corneum) and increased skin
hydration.
High ratio of total body surface area to total
body weight increased exposure can produce
toxic effects after topical use
Eg: salicylic acid ointment and rubbing alcohol

10

D
Total
Body
Water
Plasma
Protein
Binding
Body
Fat

94% in the fetus, 85% in premature infants,

78% in full-term infants, and 60% in adults.
Water soluble drugs has higher Vd
(eg:Gentamicin)
Neonates and infants have lower serum albumins
and this may affect highly protein bound drugs
The decrease in plasma protein binding of drugs
can increase their apparent Vd
(eg: phenytoin)
Amount of body fat is lower in neonates.
Fat soluble drugs has lower Vd highly lipidsoluble drugs are distributed less widely in
infants than in adults.
(eg:Diazepam)
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12

Drug metabolism is substantially slower in

infants compared with older children and
adults.
Less maturation of various pathways of
metabolism within a infant.
E.g. :- sulfation pathway is well developed but
the glucuronidation pathway is undeveloped in
infants.
The cause of the tragic chloramphenicolinduced Gray baby syndrome in newborn
infants is a decreased metabolism of
chloramphenicol by glucuronyl transferases to
the inactive glucuronide metabolite.

13

 Gray Baby Syndrome

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The processes of glomerular filtration, tubular

secretion, and tubular reabsorption determine
the efficiency of renal excretion. These
processes may take several weeks to 1 year
after birth to develop fully.
Glomerular filtration rate is about 24 mL/min
per 1.73 m2 in term infants.
Glomerular filtration rate is 90-120 mL/min per
1.73 m2 in adult.
In
infants,
if
possible
then
avoid
Chloramphenicol
and
Aminoglycoside
(gentamicin,amikacin,and etc), because their
metabolites are accumulated due to immature
function of kidney.

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Drug therapy in pediatrics

1. Dose calculation
2. Choice of dosage form
3. Adverse reaction

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 Six Rights of Pediatric Medication

Administration

RIGHT patient
RIGHT medication
RIGHT dose
RIGHT route
RIGHT time
RIGHT documentation

17

Pediatric Drug Therapy

Color preference
Pink Color
Orange Color
Yellow Color
Taste preference
Strawberry
Orange
Bubble gum
Sweet
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1. Dose calculation : Height and Wt growth are rapidly changing

factors in childhood, which also influence
significantly some pkinetic parameters. So, this
factors should be considered during therapy. So
dose calculation is needed.
Doses should be obtained from pediatric book
for children.. For example, In india IAP-Drug
formulary is reliable source for pediatric
practice and their important drugs.
For many years, pediatric dosage calculations
used pediatric formulas such as Frieds rule,
Youngs rule, and Clarks rule. These formulas
are based on the weight of the child in pounds,
or on the age of the child in months, and the
normal adult dose of a specific drug.
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1) Youngs Rule :- (based on age)




Pediatric dose =

 

2) Frieds Rule :- (Age adjustment for infants)




Infant Dose =


3) Clarks Rule :- (based on body weight)




Pediatric Dose =

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2. Choice of Dosage form :Oral Route

Tablets are less convenient
Liquid preparation are easy to administer in
accurate dose and to form in desirable dose
by dilution
Parenteral Route: Site of Access
Safety from fluid overload
Aware about Excipients
Painfull
Rectal Route
The rectal route absorption is probably
Other routes
like.
similar
to that of the upper part of GI tract.
Useful for infant that unable to take orally.
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4. Adverse reaction in therapy : Mechanism is not cleared in adverse effect of

many drugs in child. But it may be due to
immature pkinetic parameters and some
medication errors.
Some well known adverse effect
Tetracycline  Teeth brown coloration
Corticosteroids  Growth suppression in Prepubertal
child.
Paradoxical hyperactivity in child with phenobarbital
treatment
Aspirin treatment  Reyes syndrom

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23

Summary

Main key Points covered in topic..

Children are not small adults
Patient details such as age, weight and surface
area need to be ensure appropriate dosing
Weight and surface area may change
significantly in a relatively short time period
Pharmacokinetic changes in childhood are
important and have a significant influence on
drug handling and need to considered when
choosing an appropriate dosing regimen for a
child
The use of an unlicensed medicine in children is
not illegal although it must be ensured that the
choice of drug and dose is appropriate.
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References

1) Parthasarthi G, Hausen KN and Nahata MC. Pediatric

pharmacy practice. In parthasarthi G, Hausen KN and
Nahata MC edited A textbook of clinical pharmacy
practice, 1st Edition. Universities Press Private Ltd,
2008; 160-189.
2) EMEA 2005 Reflection paper: formulations of choice
for the paediatric population. European Medicines
Evaluation Agency, London. Available online at:
www.eniea.eu.int/pdfs/human/peg/19481005en.pdf
3) International Committee on Harmonization 2000 Note
for guidance on clinical investigation of medicinal
products in the paediatric population. European Agency
for the Evaluation of Medicinal Products, London
4) McIntyre J. Conroy S. Avery A et at 2000 Unlicensed
and off label prescribing of drugs in general practice.
Archives of Disease in Childhood 83: 498-501

25

5) National Institute for Clinical Excellence 2000 Guidance

on the use of inhaler systems (devices) in children under
the age of 5 years with chronic asthma. Technology
Appraisal No 10. National Institute for Clinical
Excellence. London
6) National Institute for Clinical Excellence 2002 Asthmainhaler devices for older children. Technology Appraisal
No 38. National Institute for Clinical Excellence, London
7) Scott E, Swanton J, McElnay Jet al 1995 Pharmacists
and child health. Centre for Pharmacy Postgraduate
Education/HMSO, London
8) Turners. Longworth A, Nunn A J et al 1998 Unlicensed
and off-label drug use in paediatric wards: prospective
study. British Medical Journal 316:343-345
9) Yeung S C, Ensom M H 2000 Phenytoin and enteral
feedings: does evidence support an interaction? Annals
of Pharmacotherapy 3(7-8): 896-905
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VS
Benadryl Adult
Diphenhydramine 14mg in 5ml
Adult Dose 5ml-10ml QID
Peads Dose 2.5ml -5ml QID

Benadryl Peads
Diphenhydramine 7mg in 5ml
2yr-6yr old dose 5ml-10ml QID
6yr-12yr old 10ml-15ml QID
Not recommended to child
below 2years old

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Anti-Emetic
Promethazine 1mg/ml
2yr 5yr old 5ml-15ml OD
5yr-10yr old 10ml-25ml OD
Not recommended to
child below 2years old

Piriton
Chlorpheniramine 2mg/5ml
2yr 6yr old 2.5ml QID
6yr 12yr old 5ml QID
Not recommended to child
below 2years old
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GBH 0.1% lotion

Anti Lice
Neurotoxicity can cause
seizure and death

EBB lotion 25%

Anti scab and Anti lice
Pediatric dilute to 12.5%

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Steroid Cream
Hydrocortisone 1%
For More than 1yr old pt only
Max 1 week treatment
Betamethasone
For more than 12yr old pt only
Side Effect
Pituitary and adrenal suppression
Impair a child's growth
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LMS oitment
Contain Methyl Salicylate Oil 25%
For pt more than 12yr old only
Avoid in children
Reye syndrome

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SAO 20%
Keratolytic for warts and corn
For pt more than 2yr old only

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SSD Cream 1%
Antibiotic cream for application to burns
wound.
For pt more than 2yr old only
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