1
Q
What % of the population are <18 years of age?
A
25%
2
Q
What % of children are in one-parent families?
A
25%
3
Q
What does pre-term mean?
A
Born before full term
4
Q
What differences in children do you need to consider when reviewing medication compared to adults?
A
- Different size, shape, composition and surface area- different volume of distribution
- Organs are immature and still developing
- Psychological differences- they think differently
- Nutritional status
- PK and PD - different enzyme levels for drug metabolism and handling
- Rely on parents administrating medicines if they cannot take them
- Children may be a carer for other children/family e.g. language barrier
- Formulations are different
- Smaller and lighter in weight usually- massive differences between age and need to consider obesity problem
- May be more difficult to find the problem if they cannot express how they are feeling/what the problem is
- Need to think about medicines affecting growth e.g. steroids
5
Q
At what age does brain development stop?
A
25
6
Q
What the routes of administration for children?
A
Anything adults can have, however rectal administration is generally not first line in our culture
7
Q
How does oral administration and absorption differ in children?
A
- Taste of medicines
- Risk of choking- being able to swallow tablets
- Stomach emptying and transit time is very slow
- Therefore, onset of action will be slow. If you want something to work straight away, you would not give it orally
- As it is held in the stomach longer, you may get greater absorption as there is more chance to (compared to it moving through quickly)
- Decreased absorption of basic drugs
- However, <2 years old, stomach is more alkaline (at birth, starts off at 7 and by 2 years it goes to 4-4.5) so acidic drugs will be less absorbed <2 years
- Pre-term babies can take drops
8
Q
In children there will be a decreased absorption of basic drugs due to slower gastric emptying. Name a drug that will be affected.
A
Ketoconazole
9
Q
In <2 years, the stomach is more basic therefore acidic drugs will be less absorbed. Name a drug that will be affected as it needs an acidic environment for absorption.
A
Metronidazole
10
Q
How does topical administration and absorption differ in children?
What is the risk?
A
- Immature epidermal barrier
- Increased skin hydration
- Higher surface to body weight ratio
- Therefore, greater rate and extent of absorption
- Pre-term babies have translucent thin skin
- Can lead to systemic toxicity as the drug can be absorbed into circulation rather than staying in the dermis
11
Q
Name some topical formulations for drugs
A
Creams
Patches
12
Q
Topical administration can lead to systemic toxicity in children. Name two examples of drugs.
A
Corticosteroids and chlorehedixine
13
Q
How does parenteral administration and absorption differ in children?
- IV
- IM
A
- IV
- Smaller veins- greater risk of emboli, infection, inflammation of veins (phebitis)
- May want to consider giving it slower or diluting the dose - IM
- Less muscle mass therefore unpredictable absorption and very painful
- Muscle is poorly perfused, medicine is locked at the site and therefore drug is released very slowly into systemic circulation
- Children tend to not have a lot of muscle until puberty
14
Q
Name parenteral formulations
A
IV and IM e.g. vaccines, Vitamin K to help clotting
15
Q
How might you administer an IM ABX in children?
A
Give it in 2/3 different sites e.g. 0.5 mL each
16
Q
In children, muscles are poorly perfused and IM formulations can result in the drug being locked at the site preventing absorption. Name a drug where this has been an advantage?
A
Vitamin K (phytomenadione) in neonates to provide sustained drug release
17
Q
How does body composition (water vs fat content) differ in children and how does this affect drug dosing?
A
- Water % is higher in children so you will need a higher water soluble drug dose. This is because you want to get the drug out of the water environment into cells
- Fat content is lower in children than adults, however peaks at 1 year old then goes back down again.
Fat soluble drugs will move from water environment into cells (veins to fatty deposits) so is less of an issue - However, what if the child is obese?
18
Q
When do you start to think about changing a child’s dose to an adult dose?
A
When they have finished puberty, but only if their weight is within the range of an adult
19
Q
What is distribution affected by?
A
- Rates of absorption
- Penetration of biological membranes e.g. BBB is thinner in neonates and children therefore more permeable
- Perfusion of organs
- Where is the drug going to go?
- Drug’s affinity for protein binding
20
Q
The BBB is more permeable in children. What might you do when giving a child a drug that crosses the BBB?
A
Reduce dose
Split dose
21
Q
Does gentamicin distribute in the extra cellular fluid or total body water?
A
ECF
22
Q
Does theophylline distribute into extra cellular fluid or total body water?
A
Total body water
23
Q
How does protein binding affect drug absorption in children?
A
- Highly protein bound will have less free (active) drug
- Children have fewer plasma proteins so a lot more of the drug is available to exert its action
- If there is less protein available for drug binding, there is increased competition of these binding sites. Therefore, endogenous substances can get displaced e.g. bilirubin
- Therefore, some unusual medicines are used in children
24
Q
What is the effect of a build of bilirubin?
A
- Jaundice
- CNS toxicity from deposition of unconjugated bilirubin in the brain, particularly in the basal ganglia
- High levels of bilirubin in the brain- Kernicterus and can cause brain damage
25
Are sulphonamides highly protein bound?
Yes- can displace bilirubin
26
Is ceftriaxone highly protein bound?
What is an alternative?
Yes- can displace bilirubin
Cefotaxime
27
Phenytoin is a highly protein bound drug. What are the target plasma levels for it in neonates vs children and adults?
Neonates = 6-12 mg/L
Children and adults = 10-20 mg/L
28
How is metabolism different in children?
Hepatic CYP450 enzyme function develops slowly
Phase 1 is immature at birth with the full capacity reached by 6/12 months
Phase 2 is immature at birth with the full capacity reached at 3 years
29
What is Phase 1 metabolism and give examples?
- Simple changes to the molecule
- Immature at birth but matures by 6/12 months
- Oxidation and reduction e.g. theophylline is metabolised to caffeine. Therefore < 6 months, have to give straight caffeine
- Hydrolysis - diazepam, phenytoin, phenobarbitone
30
Diazepam half life decreases with age. True or false?
True
31
What is Phase 2 metabolism?
- Immature at birth with the full capacity reached 3 years
- Acetylation,
- Glucuronidation e.g. chloramphenicol cannot be given <2 years due to grey baby syndrome
- Sulphation - paracetamol is metabolised by a different route in <12 years
32
How does excretion differ in children and how are the nephrons developed during gestation?
- Adolescents excrete medicines better than adults usually as they are at their peak and no decline with age, with no lifestyle implications e.g. smoking and drinking
- Wide variation so difficult to predict drug clearance
- 8 weeks gestation: some functional nephrons
- 26 weeks- all present but decreased size and function
- 36 weeks - nephrons are fully developed
33
What is the GFR rate in:
1. Term infant
2. Pre-term > 1kg
3. Pre-term < 1kg
1. 40 mL/min
2. 2-3 mL/min
3. 0.5 mL/min
34
What is a side effect of the antibiotic tetracycline in children?
Causes permanent staining of teeth in < 12 years as it deposits in the bone
AVOID
35
What is a side effect of metoclopramide in children?
Extra-pyramidal side effects in < 20 years
36
When does a child become an adult?
- Usually around 16 but this depends on capacity
| - Social and medical problem
37
How is acyclovir licensed in children?
- Licensed in topical formulation
- Not in IV
- Not oral- but this does not have a specified age range in the licensing
38
What should you dose on is drug has a narrow therapeutic index?
Weight
39
What can you dose on if a drug has a wider therapeutic index?
Weight
Age
40
What are advantages and disadvantages of dosing based on age?
- No calculations involved
- However, what if the child is small/large for their age?
- Some drugs have wide age ranges for their doses e.g. amoxicillin- is that tailored?
41
Drugs can be dosed based on weight. What are the 3 ways of this and give examples of drugs?
1. Calculated by weight e.g. mg/kg Ceftriaxone IV
2. Weight banded e.g. 10-15 kg Oseltamivir PO
3. Age banded then calculated by weight e.g. for 1-2 years, it is X mg/kg
Cetirizine PO
42
How is aciclovir for viral encephalitis dosed?
Body surface area
43
How do you calculate body surface area?
Square root of
(Weight kg x Height cm)/3600
44
When choosing the right dose and frequency, what do you need to consider (particularly about the dose?)
How wide is the therapeutic margin?
Is the dose measurable e.g. calculated liquid might be so small and need to round up
Is the dose sensible? What mg tablets is the drug available in- do you need to round up?
45
If you opened up a capsule and dissolved the contents, what will happen if it is not water soluble?
It will clump
46
If there are more procedures to edit the formulation, there is more risk. True or false?
True
47
When crushing tablets, what do you need to consider?
- Stability
- Some MR matrix tablets that are evenly distributed are okay to cut in half
- If it is not within a matrix/not uniform/protective layer that makes it MR, they cannot cut in half
- If you take contents from MR preparation, you need to remember is is immediate release now and need more frequent dosing but need to consider if dose is suitable
- Changing the way a dosage form is presented alters absorption characteristics, medicine stability, may produce local irritant effects
- Will it still reach site of action?
- What will the taste be like?
- May produce occupational health and safety issues
- If you are dissolving a tablet in water and giving a fraction of it to give a reduced dose - highly variable dosing and not very reliable
48
If you take contents out of a MR capsule, what do you need to consider?
It is no longer modified release - immediate release
- Need more frequent dosing but need to lower dose possibly
49
Where no appropriate licensed medicine is available, what should you try and give the patient?
Ready to use unlicensed medicine
Little guidelines due to little evidence
50
Excipients can also have an effect in formulations for children. How can the following have an effect:
1. Ethanol
2. Benzyl alcohol
3. Propylene glycol
1. Can be high in some formulations e.g. 38% in phenobarbitone liquid
2. Can cause circulatory collapse e.g. amiodarone, heparin, clonazepam, lorazepam, clindamytin, diazepam, diclofenac
3. Can cause seizures- present in phenytoin, GTN, phenobarbital and diazepam
51
What is an unlicensed medicine?
e.g. no license in the UK
or has a license but needs to be used in an unlicensed formulation e.g. crushing tablet
no MA
Important to obtain consent from parent
52
What is an off-label medicine?
Used outside its MA
For a different indication
Being used for an age group outside license e.g. elderly, children
Using a medicine at a higher dose stated in the license
Important to obtain consent from parent
53
70% of adult preventable deaths are the behaviours initated/reinforced in adolescence. True or false?
True
Brains are still developing so healthy behaviours can be established
Small, manageable repeated interventions
54
What is an adolescent's vocab like?
Less words in their vocab
Jargon
55
What is a medication error?
Preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in control of the HCP, patient or consumer
56
What are the 3 most common medication errors?
1. Wrong dose/strength/frequency
2. Omitted missed doses
3. Wrong medicine
Especially if weight is quoted in pounds rather than kilograms when they are younger, can lead to wrong calculations
57
In terms of medication errors in children, what are the 6 most common drugs?
1. Paracetamol
2. Gentamicin
3. Morphine
4. Vaccines
5. Insulin
6. IV fluids
58
What formulation carries the most error risk?
IV
59
What are the 3 main issues in paediatric IV therapy?
1. Displacement values- if the dose of a drug is less than one complete vial, so the vial requires constitution
2. Flushing of lines - in adults is it usually 5-10 mL but in neonates it is 0.2-0.5 mL
3. Dilution issues- need to remember dead space in hub of syringe e.g. if drawing up to 0.05 mL mark, the syringe will contain 0.14-0.18 mL of drug
60
Determining the risk of an IV infusion is based on the NPSA 20 risk assessment tool.
How do the number of risk factors associate with the risk category of the product?
> 6 - high risk
3-5 moderate risk
1-2 - lower risk
61
What are the 8 risk factors associated with IV infusions in the NPSA 20 risk assessment tool?
```
Therapeutic risk
Use of a concentrate
Complex calculation
Complex method
Reconstitution of powder in a vial
Use of a part vial or ampoule
Use of a pump or syringe driver (accuracy)
Use of non-standard giving set/device required
```
CDM
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