Paediatric pharmacology Flashcards
What is a premature baby?
born at less than 37 weeks gestation
What is a full term baby?
born between 37 and 42 weeks
What is neonate?
aged up to 4 weeks old
What is an infant?
1 month to 1 year old
What is a child?
between 1 and 12 years old
What is a young adult?
teenager
How do you prescribe?
- decide to give drug to treat a problem
- ensure right dosage for patient
- PHARMACEUTICS: for adults can give tablet, but for children tablet might be a suspension (powder in water), chewable or melt
- PHARMACOKINETICS- make sure drug gets to right part in body
- PHARMACODYNAMICS
- monitor how drug leaves body
What affects the drug dose and response?
- growth and development of organs in the child
- absorption of the drug in the body
- distribution of the drug in the body
- metabolism of the drug in the body
- excretion of the drug from the body
How can a drug be absorbed?
- oral
- IM
- percutaneous (through skin)
- rectal
- IV
How can distribution vary?
- depend on protein binding?
- volume
- fat distribution
Where are oral medications absorbed?
GI
What affects GI absorption in a baby?
- have reduced gastric acid secretion
(reach normal when 3yo) - gastric empty rate is slow= drug stay in tract for longer= longer effects = so need to give smaller doses
- intestine development
- GI tract disorders affect absorption
What is gastroschisis?
- in neonates sometimes
- born with gut on outside of body
- need to think of alternate route to give drugs
IM drugs are absorbed where?
Muscle
- mainly IM is given when IV isnt possible
How are drugs absorbed by the muscle?
- no pattern
- absorb depends on:
MUSCLE PERFUSION
MUSCLE CONTRACTION
MASS
NON VASCULAR TISSUE
Are IM drug administration encouraged in neonates?
- no
- painful
If drugs are applied topically, how are they absorbed?
- through the skin
How is the drug absorbed through the skin in babies?
- babies have thinner stratum corneum than adults
- this is worsened if neonatal skin is burns/damaged (scratching)
-babies also have increased skin hydration and surface area
- faster drug absorbing
- absorb higher quantities
If the baby is given corticosteroids, what can it cause?
- systemic effects:
- cushingnoid symptoms
- thinning of the skin
- weakness
- weight gain
- bruising
- hypertension
- diabetes
- thin weak bones (osteoporosis)
- facial puffiness
- stopping of menstrual periods
What can happen if a baby is given aminoglycosides?
e. g. polymyxin creams
- lead to permanent hearing loss
If a drug is given through anus (suppository), how is it absorbed?
rectally
Why is the rectal absorption pattern irregular in babies?
- babies have variations in the venous drainage of the rectum
- so irregular patterns of absorption
Why is rectal absorption useful?
- if vomiting
- if nil by mouth
- if children reluctant to take oral medications
Why is rectal not popular/convenient?
- more accessible in babies than teens
- need to consider dignity of patient
Explain IV drugs:
- 100% bioavailability (body absorbs all drug given(
- common
What are the issues with IV drugs?
- hard to access babies to put cannula
- compatibility= IV drugs shouldn’t interact to give precipitation = which can harm patient
Who has higher total body water?
- higher in neonates and infants
What are children’s water compartments like?
- their adipose tissue (fat) have higher ratio of water to lipid (more water than fat)
- premature neonates have 57% water and 35% fat in adipose tissues
- adults have 26% water and 72% fat in their adipose tissues
- babies have large extracellular fluid compartment
(it is 40% of body weight at term, and 20% of weight at 3 months old)
Why do you need to give high dose of drug to baby?
- need higher doses on a mg/kg basis to achieve steady state (keep the drug level steady in the blood)
- depend how fast the drug is cleared from the body
How much water in body at different stages of life?
−premature babies have 85% water, with 50% in ECF, 35% in ICF and are 3% fat
−term babies have 75% water, with 45% in ECF, 30% in ICF, and are 12% fat
−4 month babies have 60% water, with 30% in ECF, 30% in ICF and are 30% fat
−adults have 60% water, with 20% in ECF, 40% in ICF and are 18% fat
What do babies have less off which can affect drug distribution?
- newborns have much lower plasma protein concentration
- so drugs dont bind to proteins
- so more free drug in the blood (free fraction)
- so more drug conc in the plasma
- so therepeutic drug concs can be toxic in neonates
There are high concentrations of endogenous substances in the blood of new borns. What effect does this have?
- endogenous= substances produced in the blood
- they usually bind to proteins in blood
- but some drugs displace the substances
e.g. drugs displace bilirubin from binding sites on plasma proteins= lead to kernicterus (brain damage bc of excess free bilirubin in blood)
What can high concentrations of bilirubin do?
- displace drugs like phenytoin from plasma proteins
- so get increased conc of free drug in plasma
What can malnutrition lead to?
malnutrition would lead to hypoalbuminaemia (reduced albumin concentration in blood)
What is kwashiorkor and what does it cause?
kwashiorkor disease which is an extreme form of malnutrition would lead to hypoalbuminaemia
What is the BBB like in newborns?
less functional
What could the lack of functionality of the BBB in newborns lead to?
- more drug penetration
What affects penetration of drug?
- solubility
- ionization
- acidosis
- alkalosis
- hypoxia
- hypothermia
What are the pathways of metabolism?
- hydroxylation (phase I)= MAKE REACTIVE
- deficient in neonates
- matures rapidly
PHASE 2= MAKE SOLUBLE= CONJUGATION
- sulphation and methylation (phase II)
- similar to adults - glucoronidation (phase II)
- immature
- reach adult values by 6-18 months old
What drugs are metabolised by glucoronidation?
- chloramphenicol:
- indomethacin:
What can chloramphenicol cause in babies?
- lack of metabolism in babies
- accumulates
- turns baby grey
‘‘grey baby syndrome’’
What can indomethacin lead to in babies?
- NSAID
- lack of metab
- platelet dysfunction
How is paracetomol metabolised in babies compared to adults?
children=sulphation
adults= glucoronidation
What is theophylline metabolised to in neonates?
- to caffeine
- active metabolite of the drug
- easier to monitor than theophylline bc has wider therepeutic indec
What is GFR like in a baby?
- GFR more mature than tubular absorption in baby
- drug clearance primarily dones by GFR in frist few weeks of life
= this alters elimination rate of certain drugs e.g. penicillin and gentamycin
− in neonates we would give gentamycin every 36 hours, whilst in children we would give it every 24 hours because they do not clear the drug well enough which could lead to toxicity
What causes ADRs in children?
- immature liver function= preventing detoxification and excretion
- high drug conc accumulate in plasma
- diff metab pathways in children compared to adults
- lack of clinical trial on children- so little information on drug effects on children
What do sulphonamides cause?
- may lead to kernicterus in new borns (excess bilirubin leading to neurological damage)
- may not lead to kernicterus in older babies (as there is no excess bilirubin in older babies because they are no longer changes from HbF to HbA)
