paediatric clinical pharmacology

Question 1

why are there differences in responses to medications in children

Answer 1

altered pharmacokinetics and pharmacodynamics

Question 2

why are there differences in responses to medications in children

Answer 2

altered pharmacokinetics and pharmacodynamics

Question 3

why is safe medications use in paeds difficult

Answer 3

• lack of acute dosage data
• lack of appropriate formulations allowing accurate dosage and delivery
• difficulty in detecting ADR
• in utero exposure and transplacental transfer
• BF infants affected by maternal medication

Question 4

key points for prescribing in paeds

Answer 4

• use most simple dosage regimen
• pay attention to formulation, route, duration of therapy
• involve parents
• check BNFc

Question 5

involving parents in prescribing

Answer 5

• provide info about disease, treatment and dosage regimen
• is therapy needed? what can be expected from drug
• length of treatment
• how to monitor efficacy and ADRs

Question 6

legislation re. paeds prescribing

Answer 6

• 20% drugs ineffective for children (despite effectiveness in adults)
• 30% cause unanticipated SEs (some potentially lethal)
• 20% required dosages different from those that had been extrapolated from adult doses

Question 7

off label and unlicenced drugs

Answer 7

• off label = iicensed for human use but not for use in children below certain age or via a certain route or for a certain disease
• unlicensed = no licence for human use in this country (incl licensed medicines which are reformulated for easy use in children)

Question 8

reasons for off label prescribing

Answer 8

• formulation administered via a route not intended
• medicines used for an indication not intended
• different dose to that recommended
• children below stated recommended age limit
• medicines w/o licence - incl those designed for children or in clinical trials

Question 9

how common is off label prescribing

Answer 9

hospital:

• 60-90% off label in neonates
• 10-50% in children

community:

• 30% of children prescribed an off label medication
• 6-10% of all medications used to treat children in GP

Question 10

impacts of off label prescribing

Answer 10

when prescribing medications in children there is often little/no robust data available describing efficacy, toxicity or ADRs

• off label medication use → increased rate of ADRs and avoidable deaths

Question 11

why is extrapolation from adult data unsafe

Answer 11

• pharmacokinetic differences between adults and children
• pharmacodynamic differences in responses
• unknown effects on growth and development
• different specific pathologies
• lack of patient info leaflets/summary of product characteristic info

Question 12

ADRs in paeds

Answer 12

• neonates/infants are more sensitive to drugs than adults - organ system immaturity
• neonates/infants at increased risk for ADRs
• young pts show greater individual variation

Question 13

MEC in infants

Answer 13

• w/ IV and SC injection, time spent above mec is much greater than the time in adults
• infant is far more likely to develop toxicity due to prolonged half life
• also reduced clearance of drug due to reduced metabolism and renal function → increased likelihood of toxicity

Question 14

cytochrome P450 enzymes in children

Answer 14

CYPs - metabolic enzymes in liver

peak activity isn’t reached until 20y/o

reduced metabolic enzyme activity in children

reduced hepatic metabolism

Question 15

paediatric population age groups

Answer 15

preterm - <36wks gestational age

term neonate - 0-27 days

infant - 28 days - 23mths

child - 2-11yrs

adolescent - 12-16/18yrs

Question 16

early postnatal period

Answer 16

physiological immaturity

• rapid growth
• highly variable alterations in drug metabolism and elimination
• lower tolerance to ADRs
• difficulty in identifying efficacy and toxicity
• higher incidence of therapeutic errors
• 98% of medicines used during this phase are prescribed and used off label

Question 17

infancy

Answer 17

• extension of first stage
• type and severity of disorders being treated are different
• body weight gain and body water composition change rapidly as does ratio of body weight or SA to organ size and function

Question 18

toddler

Answer 18

• associated w/ minor illnesses
• multiple short courses of therapy
• problems w/ compliance

Question 19

young child

Answer 19

• enhanced metabolism and excretion
• clearance can change significantly during a single dose regimen
• ~30% of medicines are off label

Question 20

adolescence/young adult

Answer 20

• major changes in body size and composition which affect drug metabolism
• psychological changes and peer pressure result in behaviours which can alter drug metabolism (smoking, alcohol, drug use)

Question 21

therapeutic index in children

Answer 21

• most frequently used drugs have wide TA
• some drugs (digoxin, SSRI, anti epileptics, cytotoxics) are very toxic

Question 22

route of administration in children - oral

Answer 22

• reduced gastric acid and delayed gastric emptying in children, adult levels not reached until 3y/o
• absorption via GI tract reaches adult levels at 8mths
  
  • bioavailability of drugs w/ higher hepatic clearance and the 1st pass of elimination may be reduced and highly variable
  • drugs which rely on enterohepatic circulation are also highly variable

Question 23

route of administration in children - percutaneous

Answer 23

• enhanced in infants and children - esp w/ damaged skin/occlusive dressing
• important for steroid use - more readily and rapidly absorbed and could cause systemic effects

Question 24

route of administration in children - rectal

Answer 24

• used when vomiting/unwilling to take orally
• avoids 1st pass metabolism
• not ideal as significant variation in absorption, few preparations, risk of trauma

Question 25

route of administration in children - IV

Answer 25

delayed or uncertain delivery