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Introduction

Pharmacokinetic of Children A, D, M, E

Drug Therapy in Children Dose Calculation

Appropriate Dosage form and route

Counseling

Summary

References

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Introduction

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Pediatric means..

Day 1 1Month

(Neonate)

1- 11 years

(Children)

1 month 1year

(Infants)

Age:- 12-16

years

(Adolescents)

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

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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

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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.

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AD

MEABSORBTION

DISTRIBUTION

METABOLISM

EXCRETION

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.

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PHPH Premature Infants- Elevated pH (More alkaline) higher serum concentrations of acid-labile drugssuch as penicillin and ampicillin

Infant- Range from 6-8

Gastric

Emptying

Gastric

Emptying

Infants/Neonate:- Prolonged gastricemptying time. Drug limited absorption inadults may be absorbed efficiently in apremature infant because of prolongedcontact time with GI mucosa.

A

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 inneonate because of an underdeveloped epidermalbarrier (stratum corneum) and increased skinhydration.

High ratio of total body surface area to totalbody weight increased exposure can producetoxic effects after topical use

Eg: salicylic acid ointment and rubbing alcohol

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A

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DTotal

Body

Water

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)

Plasma

Protein

Binding

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)

Body

Fat

Amount of body fat is lower in neonates. Fat soluble drugs has lower Vd highly lipid-soluble drugs are distributed less widely in infants than in adults.

(eg:Diazepam)

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Drug metabolism is substantially slower ininfants compared with older children andadults.

Less maturation of various pathways ofmetabolism within a infant.

E.g. :- sulfation pathway is well developed butthe glucuronidation pathway is undeveloped ininfants.

The cause of the tragic chloramphenicol-induced Gray baby syndrome in newborninfants is a decreased metabolism ofchloramphenicol by glucuronyl transferases tothe inactive glucuronide metabolite.

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M

Gray Baby Syndrome

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The processes of glomerular filtration, tubularsecretion, and tubular reabsorption determinethe efficiency of renal excretion. Theseprocesses may take several weeks to 1 yearafter birth to develop fully.

Glomerular filtration rate is about 24 mL/minper 1.73 m2 in term infants.

Glomerular filtration rate is 90-120 mL/min per1.73 m2 in adult.

In infants, if possible then avoidChloramphenicol and Aminoglycoside(gentamicin,amikacin,and etc), because theirmetabolites are accumulated due to immaturefunction of kidney.

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Drug therapy in pediatrics

1. Dose calculation

2. Choice of dosage form

3. Adverse reaction

Six Rights of Pediatric Medication

Administration

RIGHT patient

RIGHT medication

RIGHT dose

RIGHT route

RIGHT time

RIGHT documentation

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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 changingfactors in childhood, which also influencesignificantly some pkinetic parameters. So, thisfactors should be considered during therapy. Sodose calculation is needed.

Doses should be obtained from pediatric bookfor children.. For example, In india IAP-Drugformulary is reliable source for pediatricpractice and their important drugs.

For many years, pediatric dosage calculationsused pediatric formulas such as Frieds rule,Youngs rule, and Clarks rule. These formulasare based on the weight of the child in pounds,or on the age of the child in months, and thenormal 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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Other routes like.

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2. Choice of Dosage form :-

Rectal Route

The rectal route absorption is probably

similar to that of the upper part of GI tract.

Useful for infant that unable to take orally.

Parenteral Route:-

Site of Access

Safety from fluid overload

Aware about Excipients

Painfull

Oral Route

Tablets are less convenient

Liquid preparation are easy to administer in

accurate dose and to form in desirable dose

by dilution

Mechanism is not cleared in adverse effect ofmany drugs in child. But it may be due toimmature pkinetic parameters and somemedication errors.

Some well known adverse effect Tetracycline Teeth brown coloration

Corticosteroids Growth suppression in Prepubertalchild.

Paradoxical hyperactivity in child with phenobarbitaltreatment

Aspirin treatment Reyes syndrom

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4. Adverse reaction in therapy :-

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Main key Points covered in topic..

Children are not small adults

Patient details such as age, weight and surfacearea need to be ensure appropriate dosing

Weight and surface area may changesignificantly in a relatively short time period

Pharmacokinetic changes in childhood areimportant and have a significant influence ondrug handling and need to considered whenchoosing an appropriate dosing regimen for achild

The use of an unlicensed medicine in children isnot illegal although it must be ensured that thechoice of drug and dose is appropriate.

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1) Parthasarthi G, Hausen KN and Nahata MC. Pediatricpharmacy practice. In parthasarthi G, Hausen KN andNahata MC edited A textbook of clinical pharmacypractice, 1st Edition. Universities Press Private Ltd,2008; 160-189.

2) EMEA 2005 Reflection paper: formulations of choicefor the paediatric population. European MedicinesEvaluation Agency, London. Available online at:www.eniea.eu.int/pdfs/human/peg/19481005en.pdf

3) International Committee on Harmonization 2000 Notefor guidance on clinical investigation of medicinalproducts in the paediatric population. European Agencyfor the Evaluation of Medicinal Products, London

4) McIntyre J. Conroy S. Avery A et at 2000 Unlicensedand off label prescribing of drugs in general practice.Archives of Disease in Childhood 83: 498-501

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5) National Institute for Clinical Excellence 2000 Guidanceon the use of inhaler systems (devices) in children underthe age of 5 years with chronic asthma. TechnologyAppraisal No 10. National Institute for ClinicalExcellence. London

6) National Institute for Clinical Excellence 2002 Asthma-inhaler devices for older children. Technology AppraisalNo 38. National Institute for Clinical Excellence, London

7) Scott E, Swanton J, McElnay Jet al 1995 Pharmacistsand child health. Centre for Pharmacy PostgraduateEducation/HMSO, London

8) Turners. Longworth A, Nunn A J et al 1998 Unlicensedand off-label drug use in paediatric wards: prospectivestudy. British Medical Journal 316:343-345

9) Yeung S C, Ensom M H 2000 Phenytoin and enteralfeedings: does evidence support an interaction? Annalsof Pharmacotherapy 3(7-8): 896-905

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Benadryl Adult

Diphenhydramine 14mg in 5ml

Adult Dose 5ml-10ml QID

Peads Dose 2.5ml -5ml QID

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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

VS

Anti-Emetic

Promethazine 1mg/ml

2yr 5yr old 5ml-15ml OD

5yr-10yr old 10ml-25ml OD

Not recommended to

child below 2years old

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Piriton

Chlorpheniramine 2mg/5ml

2yr 6yr old 2.5ml QID

6yr 12yr old 5ml QID

Not recommended to child

below 2years old

GBH 0.1% lotion

Anti Lice

Neurotoxicity can cause

seizure and death

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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

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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