Paediatric Pharmacology

Question 1

What is the safe and effective use of medicines complicated by?

Answer 1

A lack of acute dosage data

A lack of appropriate formulations allowing accurate dosage and delivery

Difficulty in detecting ADRs

Question 2

What must you always do when prescribing for children?

Answer 2

Use the most simple dosage regimen.

Pay attention to formulation, route, and duration of therapy.

Involve parents in your prescribing choice

Always check with the BNFc

Question 3

What percentage of medicines have never been studied in children?

Answer 3

70%

Question 4

How may medicines be off-label for children?

Answer 4

Off label medicines are licensed for human use but not for use in children below a certain age such as 16 or18 years or via a certain route or for a certain disease

Question 5

What are unlicensed medicines?

Answer 5

Unlicensed medicines have no licence for human use in this country

This includes licensed medicines which are reformulated for easy use in children

Question 6

Why might off-label prescribing occur in paediatrics?

Answer 6

Formulation administered via a route not intended

Medicines used for an indication not intended

Medicines used at a different dose to that recommended

Children below stated recommended age limit

Medicines without a licence
including those made especially for the child or being used in clinical trials

Question 7

How common is off-label prescribing in hospital?

Answer 7

60-90% of medicines are off label in neonates

10-50% of medicines off label in children

In community:

• 30% of children are prescribed an of label medication
• 6%-10% of all medicines used to treat children in general practice are used off label

Question 8

What is the effect of using off-label medications in children?

Answer 8

Of label medicines use gives rise to an increased rate of ADRs and avoidable deaths

Question 9

What are the causes of increased ADRs in children?

Answer 9

Neonates/infants are more sensitive to drugs than adults - due mainly to organ system immaturity

Neonates/infants are at increased risk for adverse drug reactions

Young patients show greater individual variation

Question 10

What occurs in the early post natal period (0-27 days)?

Answer 10

Phase of physiological immaturity with:

• rapid growth
• highly variable alterations in drug metabolism and elimination.
• lower tolerance to ADRs,
• difficulty in identifying efficacy and toxicity.

Question 11

What is the effect of the early post natal period on therapeutic errors?

Answer 11

Higher incidence of therapeutic errors

Almost all medicines (98%) used during this phase are prescribed
and used off label

Question 12

What occurs in infancy (1-23 Months)?

Answer 12

This is an extension of the first stage, but the type and severity of disorders being treated are different.

Body weight gain and body water composition change rapidly as does the ratio of bodyweight or surface area to organ size and function.

Question 13

What happens in the toddler phase?

Answer 13

This stage is associated with minor illnesses, leading to multiple short courses of therapy.

Problems with compliance

Question 14

What happens in the young child phase (2-11)?

Answer 14

Enhanced metabolism and excretion
Clearance can change significantly during a single dose regimen.
About 30% of prescribed medicines are off label

Question 15

What happens in the adolescence/young adult phase?

Answer 15

Sexual development produces major changes in body size and composition which affect drug metabolism.

Psychological changes and peer pressure result in behaviour such as smoking, alcohol and elicit drug use which can alter drug metabolism.

Question 16

What considerations must be made when prescribing in children?

Answer 16

There is virtually no robust data available from clinical trials to clarify the appropriate use of medicines in children.

Most frequently used drugs have a wide therapeutic index
So we can get away with out this data.

However some drugs such as digoxin, SSRIs, antiepileptic drugs and cytotoxics are very toxic.

Question 17

What are the issues with oral administration of medicines in children?

Answer 17

Reduced gastric acid and delayed gastric emptying. Adult levels reached at 3 years

Absorption via the GIT reaches adult values by 6-8 months.

Bioavailability of drugs with high hepatic clearance and first pass elimination is reduced and highly variable.

Drugs which rely on entero-hepatic circulation such as cyclosporin also highly variable.

Question 18

What are the issues with percutaneous administration?

Answer 18

Is enhanced in infants and children, especially with damaged skin or an occlusive dressing.
STEROIDS

Question 19

What are the advantages and disadvantages of rectal administration?

Answer 19

Used in patients who are vomiting or who are unwilling to take oral medication.

Avoids first-pass metabolism.

Not ideal as significant variation, few preparations, trauma.

Question 20

What are the dilemmas surrounding child clinical trials?

Answer 20

Society wants to spare children from potential risks involved in research

Even well designed trials not totally risk free

However children may be harmed if they are given medications that are inadequately studied

Treatments given to children outside a clinical trial are less stringently controlled than treatments within a trial

Many medications given to children are off-label and are thus unlicensed for use in children and without pharmacologic safety data