PRESCRIBING FOR CHILDREN

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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:

§                                         Less painful than i.m. injections.

§                                         Can be uncomfortable and restrictive.

 

q       Rectal administration:          

§                                         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.

 


 


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