PHARMAKOTHERAPY

IN INFANTS AND CHILDREN

Ngatidjan

Department of Pharmacology and Therapeutics

Faculty of Medicine UGM
Lecturer in the Faculty of Medicine YMU
Processes in Drug Therapy
Pharmaceutical Process

Pharmacokinetic Process

Pharmacodynamic Process

Therapeutical Process
PHARMACEUTIC PROCESS
Determinators
Drug composition and preparation
drug pharmacokinetics pharmacodynamics
it is designed to be easy absorbed, to be used orally (tablet, capsule, caplet, film
coated tablet, sugar coated tablet, suspension, solution etc.), intramuscularly,
intravenously, sublingual (tablet), rectally (suppository, enema), etc.
it is designed to be uneasy absorbed or unabsorbed (procaine adrenaline local
anesthetics, etc.)

Drug performance patient compliance

drug
Ngatidjan color, smell, taste,PHARTHEROLDINFANTS-12
shape, dimension, drug preparation. 3
 Pharmacokinetic Process
drug administration
(dose, route / methods, frequency)

absorption, first pass metabolism, bioavailability, distribution, elimination

plasma drug / metabolite concentration

drug concentration at the site of action

Ngatidjan therapeutical / adverse effect

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 Pharmaceutical process Drug in dose form
is the drug getting into the patient?

Gastrointestinal form Parenteral

First pass
Hepatic
metabolism
Pharmacokinetic process
is the drug getting to its site of action?
Extracellular fluid
eliminasi
Tissue
site of drug
action

Pharmacodynamic process
is the drug producing the required Pharrmacological effects
pharmacological effects

Therapeutic process
is the pharmacological effet being PHARTHEROLDINFANTS-12
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translated into a therapeutic effect?
Therapeutic / adverse effects
 BODY
Tissue
blood vesel
D+T DT
Drug (D) D + Protein (P)
Kidney
DP P+D D D
M M
M

R+D DR D+E M

Liver
Site of action
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 Infants and Children
Neonate

Infancy

The toddler

Young child
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Neonate, infants and children vs. adult
Pharmaceutical aspect
they dont like injection differ in drug administration
most of them like syrup preparation differ in drug kinetics

Pharmacokinetic aspect
neonate may slow in metabolism differ in drug dose

Pharmacodynamic aspect
differ in drug sensitivity differ choosing of the kind of drug

Therapeutical aspect
prevention / prophylactic or curative
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Neonate
Rapid growth

Variable alteration of drug metabolism

and elimination

Lower tolerance to adverse drug effects

higher incidence of therapeutic error
higher incidence of adverse drug effect
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Infancy
An extension of early (first) stage

differ from the adult and elderly

need adjustment of the therapy.

Body weigh gain and water composition change

rapidly
need to adjust the dose
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The toddler
Associated with recurrent minor
illnesses
multiple short course of therapy
some problems in taking medicines

Motor skill and curiosity developed faster

most likely to be suffering from poisoned intoxicated

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Young child
Enhance of metabolism and
excretion capacity of some drugs

The capacity of metabolism and

excretion are change rapidly
most likely to be intoxicated
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Pharmaceutical factors
Most children do not like injection
oral route is most suitable in vomiting?

Oral route
are not as tablets, capsule or caplet
mostly liquid form are preferable
sweetened medicine? tend to cause carries

Precise dose is hard to be achieved approximate

C. (cochlea) adult spoon : 15 ml
cp. (cochlea pultis) soup spoon : 8 10 ml
cth. (cochlea tea) tea spoon : 5 ml
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DOSE CALCULATION
Depends on age (Youngs rule)
Dose = adult dose x [age in years : (age + 12)]

Depends on body weight (Clarks rule)

more precise
Dose = adult dose x (weight in kg : 70)
Dose = adult dose x (weight in pound : 150)

Depends on surface area

Dose = percentage (surface area rule) to adult dose
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DRUG DOSE AND SURFACE AREA
Weight Approximate Surface are Percentage of
in kg in lb / pound age (m2) adult dose

3 6.6 newborn 0.2 12

6 13.2 3 months 0.3 18
10 22.0 1 year 0.45 28
20 44.0 5.5 years 0.8 48
30 66.0 9 years 1.0 60
40 88.0 12 years 1.3 78
50 110.0 14 years 1.5 90
60 132.0 adult 1.7 102
70
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154.0 adult
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1.76 103 18
PHARMACOKINETIC FACTORS
Drug absorption
neonate low gastric acid secretion
drug absorption differ from adult
weak acid drugs is absorbed less
than those of adult
weak base drugs is absorbed more
than those of adult

older children almost the same to adult

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DRUG DISTRIBUTION
Age group Total body Extracellular Intracellular Fat
water (%) fluid (%) fluid (%) (%of weight)

Premature baby 85 50 35 1

Fullterm neonate 70 40 30 15

Infant (6 months) 70 35 35 15

Child 65 25 40 15

Young adult 60 15 45 20

Elderly adult 45 10 35 10
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PHARMACOKINETIC FACTORS
Drug distribution
protein binding
some drugs (i.e. sulfonamide) may cause Kerns icterus

interaction to bilirubin
sulfonamides displace bilirubun from plasma albumin

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 bilirubin
albumin

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drug
Pharmacokinetic factors
Drug elimination
metabolism in neonate is lower than adult

GFR and tubular function (excretion)

is lower than those of adult

half life

tend to accumulate
Ngatidjan
drug and its metabolites
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DRUG ELIMINATION
Age group Half life of diazepam (hours)

Premature baby 38 120

Fullterm neonate 22 46

Infant (1 months) 10 12

Children 1- 15 years 15 21

Adult
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DRUG ELIMINATION
Age group Half life of phenytoin (hours)

Neonate 30 60

Infant (1 months) 27

Children 1- 15 years 2 20

Adult 20 30
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 ANTIBIOTIC IN BREAST MILK
Infant / maternal (50-100%) Infant / maternal (30-50%) Infant / maternal (0-30%)

ampicillin cefamandole amikain

carbenicillin cephalotin cefazolin

methicillin streptomisin dicloxacillin

chloramphenicol clindamycin eritromisin

sulfonamide gentamisin nafcillin

trimethoprim kanamisin oxacillin

tetrasiklin tobramicin

Penicillin
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Drug usage
in nourishing woman
What aspect have to be considered?
Is there any benefit if someone give
drug for infant by mean of giving the
drug to the nourished mother?
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in nourished mother
some drugs may appear in breast milk
cause infant intoxication? no
cause any other risk for infants? yes it is allergy
therapy for the infant,
does mother have to take the drugs ?

irrational ?

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Pharmacodynamic factors
Drug target
- receptors,
- ion channels,
- enzyme system

drug effects
- therapeutic effects
- side effects
- toxic effects
is any differences from those of adult?
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Pharmacodynamic factors
Analgesics - antipyretics
- paracetamol is safe,
- acetosal Reyes syndrome,
- NSAIDs side effects

(gastrointestinal, etc.)
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Pharmacodynamic factors
Antibiotics - chemotherapeutics
- penicillin derivatives is more safe,

- tetracycline tooth coloration,

- aminoglycosides deafness

- atropine hyperthermia
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Pharmacodynamic factors

Cold remedy?
- paracetamol is safe analgesic antipyretics,

- sympathomimetics nasal obstruction,

- dextromethorphane antitusive?

- antihistamines any benefit?

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Drug preparation
drug kinetics (liquid > tablet > enteric tab)

drug concentration in the site of action

drug effect therapeutical effect

side / toxicological effect

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PHARMAKOTHERAPY

IN ELDERLY
Elderly people vs. adult
Pharmaceutical aspect
difficult to swallow differ in drug administration

Pharmacokinetic aspect
elimination lower than adult differ in drug dose

Pharmacodynamic aspect
sensitivity differ from adult choosing of drug

Therapeutical aspect
differ in drug use for therapeutic purpose
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Pharmaceutical factors
Most elderly people difficult to swallow drugs
oral route is suitable but in non-solid form

Oral route
are not as tablets, capsule or caplet
mostly liquid form are preferable
dose problems (drug concentration)?

Precise dose is hard to be achieved approximate

C. (cochlea) adult spoon : 15 ml
cp. (cochlea pultis) soup spoon : 8 10 ml
cth. (cochlea tea) tea spoon : 5 ml
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Pharmacokinetic factors
Drug elimination
metabolism in elderly is lower than adult

GFR and tubular function (excretion)

is lower than those of adult

half life

tend to accumulate
20/11/2010
drug and its metabolites
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Pharmacodynamic factors
Drug target
- receptors,
- ion channels,
- enzyme system

drug effects
- therapeutic effects
- side effects
- toxic effects
is any differences from those of adult?
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(DiPiro et al, 2012)
(DiPiro et al, 2012)
(DiPiro et al, 2012)
Some drugs are needed
Vitamine and nutrition supplements
Minerals
Enzymes
Hormones
Analgesics-antiinflammatory agents
Etc.
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Pharmacodynamic factors

Analgesics - antipyretics
- paracetamol is safe,

- acetosal g.i. bleeding,

- NSAIDs side effects

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PHARMTHERINFANTS-10
Pharmacodynamic factors
Antibiotics - chemotherapeutics
- penicillin derivatives is more safe,

- tetracycline tooth coloration,

- aminoglycosides deafness

- erythromycin g.i. colic

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Pharmacodynamic factors
Antithrombotic
(low dose ASA),

- may cause g.i. bleeding melena,

- change with other antithrombus

then back to low dose ASA

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Pharmacodynamic factors
Antitusive
(do not give codeine),
- may cause constipation,
scibala (hard feces)
- is there any benefit to give cathartics
(yes but it may cause rebound phenomenon)
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(DiPiro et al, 2012)
(DiPiro et al, 2012)
Ngatidjan
Terima Kasih
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