Pharmacology Flashcards
What is the medicines act of 1968?
States a drug must have a license before marketing
Drugs must be shown to be safe, effective & of a high quality
What does the CHM (CSM) in UK/CPMP in the EU do?
Advise whether a license should be given or withdrawn
Why can we not extrapolate from adult data about how drugs will be in kids?
Pharmacokinetic differences between adults and children
Altered pharmacodynamic responses
Effects on growth and development not known
Different specific pathologies
What % of medicines have never been studies in children?
70%
Who are off label medicines used in?
Licensed for human use but not for use in children under certain ages (e.g. 16 or 18)
What are unlicensed medicines?
Medicines with no license for human use in this country
What things are included under medicines being used unlicensed/off label?
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
Off label use of drugs in kids is really high. But what does it lead to?
Increased rates of ADRs, incl. death
Why are neonates more sensitive to drugs that adults?
Organ system immaturity
What other issues are there in prescribing neonates/infants?
Increased risk of ADRs
Greater individual variation
Almost all medicines used in the neonatal period are use off label. Why are they not licensed for this age group?
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
What should you take into consideration when prescribing for an adolescent?
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
What should you take into consideration when prescribing for a young child?
Enhanced metabolism/excretion
Clearance can change significantly during single dose regime
Off-licensed use of paroxetine in children with depression is assoc. with what?
4x higher rate of suicide
How is the oral absorption different in kids compared to adults?
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
How is percutaneous absorption different in kids?
Enhanced
When do we use rectal preparations in kids?
Vomiting/unwilling to take oral meds
Avoids first pass metabolism
How does the body composition of a child differ from adults?
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
How is drug distribution to the neonatal brain different from adults?
Not fully developed BBB
Drugs have relatively easy access to CNS
Specifically sensitive to CNS toxicity
How does elimination differ in the neonate?
Liver immature, so longer half life if eliminated by liver
So longer time to reach steady concentration
Same with drugs eliminated by the kidney
What is hepatic metabolism like in the neonatal period?
V. slow (due to immaturity of metabolising enzymes)
Oxidation & glucuronidation are reduced
Reaches adult level within 1y
In the older child which drugs may need to be in higher doses and why?
Some drugs, e.g. anti-epileptics need to greater on mg/kg basis as hepatic metabolism is faster and t1/2 shorter
What metabolic disturbances increase the sensitivity to drugs?
Fever
Dehydration
Acidosis (decreased cellular penetration of basic drugs)
How can side effects of drugs be reported?
Yellow card system
How might you check drug advise for kids?
BNF for children
