Clinical Pharmacology and Therapeutics

54 DRUGS IN INFANTS AND CHILDREN
The infant should be monitored if β-adrenoceptor antagonists,
carbimazole, corticosteroids or lithium are prescribed
to the mother. β-Adrenoceptor antagonists rarely cause significant
bradycardia in the suckling infant. Carbimazole should
be prescribed at its lowest effective dose to reduce the risk
of hypothyroidism in the neonate/infant. In high doses,
corticosteroids can affect the infant’s adrenal function and
lithium may cause intoxication. There is a theoretical risk of
Reye’s syndrome if aspirin is prescribed to the breast-feeding
mother. Warfarin is not contraindicated during breast-feeding.
Bromocriptine suppresses lactation and large doses of
diuretics may do likewise. Metronidazole gives milk an
unpleasant taste.
PRACTICAL ASPECTS OF PRESCRIBING
COMPLIANCE AND ROUTE OF ADMINISTRATION
Sick neonates will usually require intravenous drug administration.
Accurate dosage and attention to fluid balance are
essential. Sophisticated syringe pumps with awareness of
‘dead space’ associated with the apparatus are necessary.
Children under the age of five years may have difficulty
in swallowing even small tablets, and hence oral
preparations which taste pleasant are often necessary to
improve compliance. Liquid preparations are given by means
of a graduated syringe. However, chronic use of sucrosecontaining
elixirs encourages tooth cavities and gingivitis.
Moreover, the dyes and colourings used may induce hypersensitivity.
Pressurized aerosols (e.g. salbutamol inhaler, see Chapter
33) are usually only practicable in children over the age of ten
years, as co-ordinated deep inspiration is required unless a
device such as a spacer is used. Spacers can be combined with
a face mask from early infancy. Likewise, nebulizers may be
used to enhance local therapeutic effect and reduce systemic
toxicity.
Only in unusual circumstances, i.e. extensive areas of
application (especially to inflamed or broken skin), or in
infants, does systemic absorption of drugs (e.g. steroids,
neomycin) become significant following topical application
to the skin.
Intramuscular injection should only be used when
absolutely necessary. Intravenous therapy is less painful, but
skill is required to cannulate infants’ veins (and a confident
colleague to keep the target still!). Children find intravenous
infusions uncomfortable and restrictive. Rectal administration
(see Chapter 4) is a convenient alternative (e.g. metronidazole
to treat anaerobic infections). Rectal diazepam is particularly
valuable in the treatment of status epilepticus when intravenous
access is often difficult. Rectal diazepam may also be
administered by parents. Rectal administration should also be
considered if the child is vomiting.
Paramount to ensuring compliance is full communication
with the child’s parents and teachers. This should include
information not only on how to administer the drug, but
also on why it is being prescribed, for how long the treatment
should continue and whether any adverse effects are
likely.
Case history
A two-year-old epileptic child is seen in the Accident and
Emergency Department. He has been fitting for at least 15
minutes. The casualty officer is unable to cannulate a vein
to administer intravenous diazepam. The more experienced
medical staff are dealing with emergencies elsewhere
in the hospital.
Question
Name two drugs, and their route of administration,
with which the casualty officer may terminate the convulsions.
Answer
Rectal diazepam solution.
Rectal or intramuscular paraldehyde.
DOSAGE
Even after adjustment of dose according to surface area,
calculation of the correct dose must consider the relatively
large volume of distribution of polar drugs in the first four
months of life, the immature microsomal enzymes and
reduced renal function. The British National Formulary and
specialist paediatric textbooks and formularies provide
appropriate guidelines and must be consulted by physicians
who are not familiar with prescribing to infants and
children.
ADVERSE EFFECTS
With a few notable exceptions, drugs in children generally
have a similar adverse effect profile to those in adults. Of particular
significance is the potential of chronic corticosteroid
use, including high-dose inhaled corticosteroids, to inhibit
growth. Aspirin is avoided in children under 16 years (except
in specific indications, such as Kawasaki syndrome) due to an
association with Reye’s syndrome, a rare but often fatal illness
of unknown aetiology consisting of hepatic necrosis and
encephalopathy, often in the aftermath of a viral illness.
Tetracyclines are deposited in growing bone and teeth, causing
staining and occasionally dental hypoplasia, and should
not be given to children. Fluoroquinolone antibacterial
drugs may damage growing cartilage. Dystonias with metoclopramide
occur more frequently in children and young
adults than in older adults. Valproate hepatotoxicity is
increased in young children with learning difficulties receiving
multiple anticonvulsants. Some adverse effects cause