Paediatric prescribing Flashcards
What is pharmacokinetics?
What the body does to the drug
What’s pharmacodynamics?
What the drug does to the body
Principles of pharmacokinetics and expand on them
ADME
A - absorption -> process of a substance entering blood circulation
D - distribution -> dissemination of the substances throughout the fluids and tissues of the body *water or fat/lipid compartment
M - metabolism -> transformation of the parent into daughter compounds
E - elimination / excretion -> the removal of the substances from the body
What can affect drug absorption in children?
Drug absorption in children can be affected by developmental changes in:
- gut pH
- gastric emptying
- intestinal drug-metabolizing enzymes
- intestinal microflora
What is the rate absorption in very young children?
Slower
Gastric pH in neonates - how is it?
In neonates and young children there is very little production of gastric pH -> therefore pH is slightly alkaline (less acidic)
Phenytoin in neonates - where is it absorbed
Phenytoin is not absorbed well in more alkaline environment -> absorption from GI tract is less effective (due to higher gastric pH)
* loading dose needed IV (in neonates) before dosing by mouth
Water compartment in infants - how is it compared to grown-ups
There is more water in infants - 80% of body weight -> then it decreases over the years
Other changes than water (affecting distribution)
Changes to:
- BBB permeability
- circulating plasma protein
What do we need to consider administrating aminophylline (in an obese person)
Aminophylline
- it is almost completely distributed in the water compartment
obese person - has more kgs, but the same amount of water (as thin) but larger lipid compartment*
- e.g. if someone is obese and we base a dose of aminophylline on actual body weight - > we may overdose of aminophylline -> arrhythmias
- therefore Aminophylline should be administrated om ideal body weight
What’s first phase metabolism
Phase I metabolism
- making a drug more active/ modifying it by: oxidation, reduction, hydrolysis or hydration
* cytochrome P450 enzymes catalyse it
What’s phase II metabolism
Phase II metabolism
- conjugation to form polar compounds (water-soluble -> can be excreted)
How are most drugs excreted?
What do we need to consider in e.g. preterm neonate?
Kidney
In a preterm neonate/ kidney impairment -> GFR may be already very low -> different/reduced dosing is required
What negative effect do aminoglycosides have?
Aminoglycosides -> are eliminated by glomerular filtration BUT they are also nephrotoxic
What do we need to consider in preterm neonates in terms of dosing aminoglycosides/ gentamycin?
Longer dosing intervals are required (especially in preterm neonates as GFR is very low)
*this is to avoid accumulation
What is the danger of opioids?
May cause respiratory depression
Management of opioid overdose
- ABCD (airway management may be needed if GCS is low)
- Naloxone (a competitive antagonist of opioid)
What are the analgesic effects of codeine due to?
It is due to codeine being metabolized into morphine
What may be the problem with codeine administration
Codeine is broken down by CYP2D6 - different alleles = different activity of these enzymes (therefore codeine may have very different effects on people e.g. maybe ultra-rapid metabolized -> OD of morphine and respiratory depression possible)
Do we use codeine in children under 12 years?
No, as they may have high (ultra-rapid metabolism) activity of enzymes metabolizing codeine -> may lead to death from respiratory depression (as metabolized to morphine and possible morphine OD in ultra-rapid metabolizers)
What’s a ‘yellow card’ scheme?
Yellow card scheme
It is a way to report adverse reaction of the drug to MHRA*
*Medicines and Healthcare Products Regulatory Agency -> they license the drugs for use in the UK
