Pharmacology

Question 1

What is the medicines act of 1968?

Answer 1

States a drug must have a license before marketing

Drugs must be shown to be safe, effective & of a high quality

Question 2

What does the CHM (CSM) in UK/CPMP in the EU do?

Answer 2

Advise whether a license should be given or withdrawn

Question 3

Why can we not extrapolate from adult data about how drugs will be in kids?

Answer 3

Pharmacokinetic differences between adults and children
Altered pharmacodynamic responses
Effects on growth and development not known
Different specific pathologies

Question 4

What % of medicines have never been studies in children?

Answer 4

70%

Question 5

Who are off label medicines used in?

Answer 5

Licensed for human use but not for use in children under certain ages (e.g. 16 or 18)

Question 6

What are unlicensed medicines?

Answer 6

Medicines with no license for human use in this country

Question 7

What things are included under medicines being used unlicensed/off label?

Answer 7

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 license, incl those being used in clinical trials

Question 8

Off label use of drugs in kids is really high. But what does it lead to?

Answer 8

Increased rates of ADRs, incl. death

Question 9

Why are neonates more sensitive to drugs that adults?

Answer 9

Organ system immaturity

Question 10

What other issues are there in prescribing neonates/infants?

Answer 10

Increased risk of ADRs

Greater individual variation

Question 11

Almost all medicines used in the neonatal period are use off label. Why are they not licensed for this age group?

Answer 11

Rapidly growing child that is physiologically immature
Highly variable alterations in drug metabolism & elimination
Lower tolerance to ADRs
Higher incidence of therapeutic errors
Difficulty in identifying efficacy and toxicity

Question 12

What should you take into consideration when prescribing for an adolescent?

Answer 12

Puberty –> changes in body size and composition (affects drug metabolism)
Psychological changes & peer pressure lead to alcohol drinking, smoking, elicit drug use etc. which can alter metabolism

Question 13

What should you take into consideration when prescribing for a young child?

Answer 13

Enhanced metabolism/excretion

Clearance can change significantly during single dose regime

Question 14

Off-licensed use of paroxetine in children with depression is assoc. with what?

Answer 14

4x higher rate of suicide

Question 15

How is the oral absorption different in kids compared to adults?

Answer 15

Reduced gastric acid & delayed gastric emptying
Bioavailability of drugs with high hepatic clearance & first pass metabolism is reduced & highly variable
Drugs relying on entero-hepatic circulation (e.g. cyclosporin) highly variable

Question 16

How is percutaneous absorption different in kids?

Answer 16

Enhanced

Question 17

When do we use rectal preparations in kids?

Answer 17

Vomiting/unwilling to take oral meds

Avoids first pass metabolism

Question 18

How does the body composition of a child differ from adults?

Answer 18

Newborns have a high extracellular fluid volume
Total body water is a lot higher
Fat content is a lot lower
Means we need larger initial doses to achieve correct plasma concentration - but may have to decrease/increase daily dose depending on hepatic function/renal elimination

Plasma proteins less –> greater active drug

Question 19

How is drug distribution to the neonatal brain different from adults?

Answer 19

Not fully developed BBB
Drugs have relatively easy access to CNS
Specifically sensitive to CNS toxicity

Question 20

How does elimination differ in the neonate?

Answer 20

Liver immature, so longer half life if eliminated by liver
So longer time to reach steady concentration
Same with drugs eliminated by the kidney

Question 21

What is hepatic metabolism like in the neonatal period?

Answer 21

V. slow (due to immaturity of metabolising enzymes)
Oxidation & glucuronidation are reduced
Reaches adult level within 1y

Question 22

In the older child which drugs may need to be in higher doses and why?

Answer 22

Some drugs, e.g. anti-epileptics need to greater on mg/kg basis as hepatic metabolism is faster and t1/2 shorter

Question 23

What metabolic disturbances increase the sensitivity to drugs?

Answer 23

Fever
Dehydration
Acidosis (decreased cellular penetration of basic drugs)

Question 24

How can side effects of drugs be reported?

Answer 24

Yellow card system

Question 25

How might you check drug advise for kids?

Answer 25

BNF for children