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
 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
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

12/11/2011
therapeutical / adverse effect
Ngatidjan, PHARMTHERINFANTS-2011 4
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 color, smell, taste, shape, dimension, drug preparation.
Ngatidjan, PHARMTHERINFANTS-2011 5
DRUG KINETICS
 Drug molecular size (MW)
 250 – 500 cross placenta easily
astemiazol 458,6 terfenadine 471,7
chlorpheniramine maleat 390,9
diphenhydramine 255,4
diphenhydramine HCl 291,8
diclophenac 296,1
ibuprofen 206,3
indomethacin 357,8
Ngatidjan, PHARMTHERINFANTS-2011 9
DRUG KINETICS

 Drug molecular size (MW)

 500 – 1.000 cross placenta easily
INH 137,1
chloramphenicol 323,1
streptomycin 581,6
erythromycin 733,9
azihromycin 785,0
benzatin penicilline 909,1
Ngatidjan, PHARMTHERINFANTS-2011 10
DRUG KINETICS

 Drug molecular size (MW)

 > 1.000

human insuline 5807.6

bovine insuline 5733.5

porcine insuline 5777.5

Ngatidjan, PHARMTHERINFANTS-2011 11
Infants and Children
• Neonate

• Infancy

• The toddler

• Young child
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 Neonate, infants and children vs. adult
• Pharmaceutical aspect
 they don’t 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 (Young’s rule)
 Dose = adult dose x [age in years : (age + 12)]

 Depends on body weight (Clark’s 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
70 154.0 adult 1.76 103
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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 Kern’s icterus

 interaction to bilirubin
 sulfonamides displace bilirubun from plasma albumin
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 bilirubin

drug

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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 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 24 – 48
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DRUG ELIMINATION
Age group Half life of phenytoin (hours)

Neonate 30 – 60

Infant (1 months) 2–7

Children 1- 15 years 2 – 20

Adult 20 – 30

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28
 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 G 29
Drug usage
in nourished 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  Reye’s syndrome,

- NSAIDs  side effects

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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

 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
39
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 drug and its metabolites

40
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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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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Pharmacodynamic factors
• Antibiotics - chemotherapeutics
- penicillin derivatives is more safe,

- tetracycline  tooth coloration,

- aminoglycosides  deafness

- erythromycin  g.i. colic

20/11/2010 Ngatidjan, PHARMTHERINFANTS-10 44
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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Terima Kasih

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