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PRESCRIBING
FOR CHILDREN
·
Children (especially neonates) do not respond to drugs like miniature
adults.
·
Special consideration must be taken of differences in body constitution,
pharmacokinetics, adverse reactions etc. when prescribing for children.
·
Important issues also exist in more practical aspects of prescribing
e.g. Compliance
Pharmacokinetics
Several factors are important when considering how pharmacokinetics
differ in children compared to adults.
1.
Drug Absorption
a)
Neonates
·
Neonates have ¯
gastric acidity. This may lead to
absorption of certain drugs (e.g. the antibiotic amoxicillin)
·
During neonatal period, gastric emptying is prolonged and may be further
delayed by disease (e.g. respiratory distress syndrome, congenital heart
disease.) Thus it takes longer for
a drug to reach a similar plasma concentration.
b)
Infants & young children
·
Oral
liquid preparations frequently used. This
results in less accurate dosing and
rate of absorption. This can be of
importance for drugs with narrow therapeutic window (e.g. theophylline) owing to
higher peak plasma concentration and adverse effects.
·
Infant skin is thin and absorption of drugs percutaneously is
relative to that of adults. \Systemic
absorption of corticosteroids from local preparations is ,
leading to possible toxicity from long-term use.
2.
Drug Distribution
·
The total body water compartment represents a larger proportion of total
body mass in neonates (~70%) compared to adults (~50-60%), and is even higher in
premature neonates (~85%). This
will affect distribution of water-soluble drugs (eg.aminoglycosides).
·
Body fat is low in children \fat-soluble
drugs have a ¯
volume of distribution (e.g. diazepam).
·
In neonates, plasma albumin concentration is ¯,
and the binding properties of albumin & globulin are altered \
binding of drugs to plasma proteins is ¯
and the proportion of drug free in the plasma will be . Free drug is responsible for pharmacological effect of drug,
and thus
drug effect or toxicity may result.
·
Sulphonamides may thus displace bilirubin from albumin causing
kernicterus.
·
Blood brain barrier - permeability
in neonates and young children \risk
of CNS adverse effects is .
3.
Drug Metabolism
·
Hepatic microsomal enzymes do not work as efficiently in neonates and
enzyme induction is reduced– this is especially marked in preterm infants.
After the first 4 weeks the enzyme system matures rapidly.
Phase I reactions achieve maturity by ~6 months.
Phase II (conjugation) reactions may not reach adult levels until 3rd/4th
year of life.
·
In children, ratio liver weight : body weight is ~2/3 that of an adult
\drugs
are metabolised less rapidly in neonates.
E.g. Chloramphenicol may result in ‘grey baby syndrome’ in neonates.
Inefficient liver glucuronidation leads to
plasma levels of the drug
4.
Drug Excretion
·
Renal excretion of drugs is ¯
in neonates (30-40% adult), however GFR
rapidly during the first 4 weeks of life, resulting in a corresponding
in drug elimination. Thus drugs
that are eliminated renally need to be given in smaller doses during the first
weeks of life.
Pharmacodynamics
·
Documented evidence about differing receptor sensitivity in children is
lacking.
Dosage of Drugs in Children
·
In the neonatal period (the first 30 days of life) care must be taken in
the calculations of the doses and attention given to fluid balance.
·
The BNF explains that the best way to calculate a child’s dose for a
particular medicine (based on the knowledge of the appropriate adult dose) is by
adjusting it for either 1) Body weight, or 2) Body surface area.
·
The publication does however say that the most reliable method of
conversion of a dose is achieved when using the body surface area as a
‘conversion factor’. The reason being that when adjusting a dose for a child
using body weight an obese child may receive a dose that is deemed higher than
necessary for the treatment of that particular condition. As a result the child
may suffer from the severe adverse effects of an overdose of that drug.
·
The BNF says that the best way to overcome that problem is by
calculating the child’s dose ‘from an ideal weight, related to height and
age’.
·
The more accurate body surface area (BSA) method of calculation uses the
following equation to work out a paediatric dose:
Paediatric dose =
Surface area of patient(m2)
x Adult dose
(approximately)
1.8
(BSA values can be calculated from the height and
weight of the child and using a
nomogram constructed by J.Insley 1996).
Adverse effects
·
The risk of toxicity by drug administration to a child is thought to
greatest when the child is in their first month of life (neonate). At this age
the child has an inefficient renal filtration system, relative enzyme
deficiencies and inadequate detoxifying systems. All of the above factors may
contribute to the delayed excretion of a drug.
There are also differing target organ sensitivities
·
As a result children easily develop the adverse effects of certain
drugs.
e.g.
- Chronic
corticosteroid use - reduced growth
- Aspirin-Reye’s
syndrome (Hepatic necrosis + encephalopathy may develop post viral illness).
- Tetracyclines
- Staining + dental hypoplasia
- Fluroquinolone
- damage to growth cartilage
- Metoclopramide
- dystonias
- Sodium
Valproate - hepatic failure.
·
Parents should be advised not to add any medicines to the infant's feed
– since the drug may interact with the milk or other liquid in it; moreover
the ingested dosage may be reduced if the child does not drink all the contents.
Breast Feeding
·
Breast-feeding can lead to toxicity in children if drug enters milk.
Drug interactions may occur between drugs prescribed to neonates and
drugs received via breast milk.
Milk [ ] of drug may > maternal plasma [ ]
but dose delivered to baby is small
but
Drug
at low dose may cause
hypersensitivity
Drug
Q.
What
drug is most likely to enter breast milk?
A.
A
lipid soluble unionised low mol wt. Molecule
Milk
Q.
What is its pH?
A.
It
is weakly acidic
OK,
SO THEREFORE DRUGS THAT ARE WEAK BASES ARE CONCENTRATED IN BREAST MILK BY
TRAPPING OF THE CHARGED FORM OF THE DRUG.
BUT
DOSE
ADMINISTERED TO THE NEONATE IN BREAST MILK IS CLINICALLY INSIGNIFICANT
·
DRUGS
CONTRAINDICATED WHILE BREASTFEEDING
These
require cessation of breast-feeding:
S
timulant
laxatives
O ctreotide
C hloramphenicol,
ciprofloxacin, cocaine, COC, cyclosporin, cytotoxics
A
spirin,
amiodarone, vit A
B enzodiazepines
E
rgotamine
T
hiazide
diuretics
·
DRUGS REQUIRING MONITORING WHEN BREASTFEEDING
These include :
ADRENOCEPTOR ANTAGONISTS
Rarely cause Bradycardia
CARBIMAZOLE
Prescribe at lowest effective dose to reduce risk of hypothyroidism
WARFARIN
Not contraindicated
CORTICOSTEROIDS
At high doses, can affect
adrenal function
LITHIUM
Can cause intoxication
ASPIRIN
Possible Reye’s syndrome
BROMOCRIPTINE
Suppress Lactation
DIURETICS
Suppress Lactation
METRONIDAZOLE
Milk tastes unpleasant
Practical Aspects of Prescribing for Children
·
Prescription Writing
§
Inclusion of age is a legal requirement in the case of prescription only
drugs for children under 12 years of age.
·
Route of Administration
q
Tablets:
§
Children under the age of 5 have trouble swallowing even small tablets.
Low compliance.
§
Oral preparations (which taste pleasant) are often necessary.
q
Liquid preparations:
§
Given by means of a graduated syringe.
§
Chronic use of sucrose containing elixirs can cause tooth cavities and
gingivitis.
§
Dyes and colourings may also cause hypersensitivity reactions.
§
Sugar free preparations are recommended for long-term treatment.
q
Pressurized aerosols:
e.g. salbutamol inhaler
§ Usually only practicable in children over 10 years old (because co-ordinated deep inspiration is required)
§
Spacers can be combined with a face mask in early infancy.
§
Nebulizers can be used to enhance local therapeutic effect and reduce
systemic toxicity.
q
Topical application to skin:
§
Under unusual circumstances (inflamed/broken skin) or in infants,
systemic absorption of drugs (e.g. steroids, neomycin) becomes significant.
q
Intramuscular injections:
§
Should only be used when absolutely necessary.
q
Intravenous injections:
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Less painful than i.m. injections.
§
Can be uncomfortable and restrictive.
q
Rectal administration:
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Often a convenient alternative.
§
e.g. rectal diazepam when iv access is unavailable.
§
Should be considered if child is vomiting.
·
Compliance
§
Non-compliance is an important
issue in paediatrics. It is
important that children understand the seriousness of their illness and that
parents and teachers are informed.