role of pharmacist in paeds Flashcards
what happens with regards to pharmacokinetics as children develop?
these key areas relating to drug action are impacted:
distribution
protein binding
metabolism
excretion
pharmacokinetics changes significantly with age
what do absorption & distribution of a drug relate to? (5)
rates of absorption
penetration of biological membranes
perfusion of organs
drug’s disposition to distribute
drug’s affinity for protein binding
why are neonates more sensitive to CNS side effects of drugs like diazepam?
because they have a more permeable blood brain barrier
therefore, take into consideration cumulative dose - do they need daily dosing? likely not, would have increased sedation
has a longer 1/2 life in babies
why are drugs that distribute in total body water (TBW) dosed lower in children?
children have greater TBW than adults so there is more free (active) drug floating around than in adults
i.e., gentamicin distributes in extracellular fluid
why is phenytoin dosed lower in neonates compared to adults?
children have less protein (lower albumin levels) and so there is less available for drug binding which means more free (active) phenytoin in the blood
why can CNS toxicity arise from protein binding drugs in children?
there is increased competition for binding sites which displaces endogenous substances such a bilirubin. this can lead to unconjugated deposition of bilirubin in the brain, particularly the basal ganglia
happens w sulphonamides and ceftriaxone in neonates
why is there a greater degree of interactions in children with protein bound drugs?
children have less albumin and so 2 drugs competing for albumin will have a greater degree of interactions as there will be more drug in the blood
what is different in terms of metabolism in children?
hepatic CYP450 enzyme functions slowly
phase 1 metabolism is immature at birth and matures by 6 months
phase 2 metabolism is immature at birth and develops slowly
when does CYP450 enzyme function typically mature in children?
phase 1 matures by 6 months; phase 2 develops slowly into childhood (fully at 12 years)
why can’t neonates have theophylline?
they do not have the metabolic pathway developed to get theophylline working (caffeine given instead to open up airways)
how does the metabolism of paracetamol differ in children <12 years?
they only have one phase 1 reactions. phase 2 metabolism does not fully develop till 12 years therefore there is an increased risk of overdose and hepatotoxicity since metabolites compete for one pathway
they have sulphation pathway but not glucourindation pathway
how does grey baby syndrome occur?
with chloramphenicol, due to the immature liver’s inability to metabolise the drug = accumulation of chloramphenicol + metabolites
poor glucuronidation (phase 2 metabolism)
how does excretion differ in children?
GFR is dramatically lower in preterms - dose adjustment
there are some functional nephrons at 8 weeks and they fully develop at 36 weeks
all nephrons are present but are not activated until around 7 days post birth
how does metabolism differ for 16-19 year olds?
this demographic may metabolise drugs better than expected due to their faster metabolism and probably clear doses faster than expected
what are 3 examples of developmental pharmacodynamics?
- earlier development of opioid receptors in medulla and pons than any other area of brain = increased risk of respiratory depression and poor analgesia in new borns
- warfarin: lower levels of protein C and thrombin prepuberty which means less warfarin would be needed (less clotting factors)
- ciclosporin: higher doses are needed to have 50% inhibition in peripheral blood monocytes in infants compared to teenagers
why was codeine use stopped in children and breastfeeding mothers?
due to risk of respiratory depression in ultra-rapid CYP2D6 metabolisers.
–> no way of knowing who these would be
what is meant by licensed?
a medicine that has been reviewed by a regulatory body to state it meets acceptable standards of efficacy, quality, and safety for use in a group of patients for a certain condition
what is meant by off-label?
prescribing a licensed product for use in a way not described in the SPC
–> even crushing a tablet = off label
legal requirement to tell pt
what is meant by unlicensed?
a medicinal product for human use that has not been officially approved for the condition it is being used for - no marketing authorisation has been granted by a relevant licensing authority
–> could be due to people with the condition being too small a number for a clinical trial
legal requirement to tell pt
what is meant by orphan drug?
a drug which is licensed with a relevant licensing authority for a condition which is extremely rare and would not be commercially viable to undertake a full licensing pathway
(for orphan disease = very rare disease)
what percentage of neonatal ICU medications are unlicensed?
80%
why is off-label prescribing common in paediatrics?
many drugs are not trialled in children, so clinicians rely on adult data and clinical experience
(lack of clinical trials in children - do not know what will happen w a lot of drugs and doses)
more than 50% drugs used in children had not been tested in children (2010)
what should you communicate to parents when using unlicensed/off-label meds?
reassure them about clinical experience, explain potential side effects, and invite questions.
what are 3 examples of developmental pharmacodynamics?
- earlier development of opioid receptors in medulla and pons than any other area of brain = increased risk of respiratory depression and poor analgesia in new borns
- warfarin: lower levels of protein C and thrombin prepuberty which means less warfarin would be needed (less clotting factors)
- ciclosporin: higher doses are needed to have 50% inhibition in peripheral blood monocytes in infants compared to teenagers
