Pharmacology Flashcards
What are differences in neonates and children’s responses to drugs due to?
Altered pharmacokinetics and pharmacodynamics
What is the safe and effective use of drugs used in children complicated by?
- A lack of acute dosage data
- A lack of appropriate formulations allowing accurate dosage and delivery
- Difficulty in detecting ADRs
How can neonates be affected by their mother’s medications?
- In the postnatal period may arise from in utero exposure by transplacental transfer
- Through breast feeding
What should you consult before prescribing in children?
BNFc
What information should parents and children be provided with when prescribing drugs?
Information about the disease, treatment and dosage regimen
What must happen before a drug become available to the public
Must obtain a license to show it is safe, effective and of high quality
Why can we not use results from trials on adults for children?
- Pharmacokinetic differences between adults and children
- Altered pharmacodynamics responses
- Effects on growth and development
- Different specific pathologies
What are off-label medicines?
Medications which are licensed for human use but are used in a way not specified in their license i.e in children below a certain age
How can medications be used 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 licence, including those being used in clinical trials
How common is off-label use in children?
In hospital
- In neonates 60-90% of medicines are off label
- In children 10-50% of medicines off label
In community
-30% of children are prescribed an of label medication
What does off-label use increase the rate of?
ADRs including death
Why are neonates and infants more sensitive to drugs than adults?
Organ system immaturity
Preterm or premature
Less than 36 week gestation age
Term new-born (neonate)
0 days until 27 days old
Infant
28 days until 23 months old
Child
2 years until 11 years old
Adolescent
12 years until 16-18 years old
What occurs during the phase of physiological immaturity in the early post-natal period?
- Rapid growth
- Highly variable alterations in drug metabolism and elimination
- Lower tolerance to ADRs
- Higher incidence of therapeutic errors
- Difficulty in identifying efficacy and toxicity
What physiological changes occur in infancy?
Body weight gain and body water composition change rapidly as does the ratio of bodyweight or surface area to organ size and function.
What issues are there with toddlers and medication?
- Stage associated with minor illnesses which leads to multiple short courses of therapy
- Problems with compliance
How does a young child handle medicine?
- Enhanced metabolism and excretion
- Clearance can change significantly during a single dose regimen.
Why is drug metabolism affected in adolescence?
- Sexual development produces major changes in in body size and composition.
- Psychological changes and peer pressure result in behaviour such as smoking, alcohol and elicit drug use
Why can off-licence medications be used in children without data from trials?
Most commonly used drugs have a wide therapeutic index
Give examples of drugs types which can be very toxic?
- Digoxin
- SSRIs
- Anti-epileptic drugs
- Cytotoxics
How may drugs be administered?
- Oral
- Parenteral
- Topical
- Rectal
How are drugs administered by the oral route affected in children?
- Reduced gastric acid and delayed gastric emptying.Adult levels reached at 3 years
- Absorption reaches adult values by 6-8 months.
- Bioavailability of drugs with high hepatic clearance and first pass elimination is reduced and highly variable.
- Drugs which rely on entero-hepatic circulation such as cyclosporin also highly variable.
How are drugs administered percutaneously affected in children?
Enhanced in infants and children specially with damaged skin or an occlusive dressing
How are drugs administered rectally affected in children?
- Used in patients who are vomiting or who are unwilling to take oral medication.
- Avoids first-pass metabolism.
- Not ideal as significant variation, few preparations, trauma.
How is delivery affected in IV administered drugs in children?
Delay or uncertain delivery
What can affect drug distribution?
- Body composition
- Plasma protein binding
How does extracellular fluid volume vary with age?
- New-born 45%
- 1 year old 25%
- Adults 20-25%
How does total body water vary with age?
- New-born 75-92%
- Adults 50-60%
How does fat content vary with age?
- Term infants 12%
- 1 year old 30%
- Adult 18%
How should drugs be given in children to achieve the correct plasma concentration?
- Larger initial doses on a mg/kg body weight need to be given to achieve correct plasma concentration.
- After the loading dose the dosage interval may need to be increased or the daily dose decreased to compensate for the decreased hepatic function or decreased renal elimination
How is plasma protein binding affected in the neonate?
Reduced leading to greater unbound/active drug
Why are infants especially sensitive to drugs that cause CNS toxicity?
- BBB is not fully developed at birth
- Drugs and other chemicals have relatively easy access to the CNS
Why do drugs take longer to reach steady state in neonates?
- In the neonate liver and kidney metabolism is immature, thus drugs eliminated by the liver or kidneys have a longer t1/2
- This results in a longer time to reach steady state (4xt1/2), an increase in steady state concentration
Why is hepatic metabolism very slow in the neonatal period?
Due to immaturity of drug metabolising enzymes
How is hepatic metabolism affected in the neonatal period?
- Very slow
- Oxidation and glucuronidation are reduced.
- Interindividual and pharmacogenetically determined differences in the rate of hepatic metabolism are seen in children.
- Sensitive to drugs eliminated by hepatic metabolism
- Metabolic activity increases rapidly from about 1 month after birth with adult activity by 1 year of age
Why do children 1-8 need higher doses of anti-epileptics than adults?
Hepatic metabolism is more rapid and t1/2 is shorter
What does renal excretion show with age?
Progressive maturation
When are adult values for renal excretion achieved?
3-6 months and tubular function by 12 months
How is t1/2 life affected by neonatal excretion?
Prolonged
What are the main differences to infant pharmacokinetics?
- Decreased albumin, increased free drug
- Increased free drug, increased response
- Decreased hepatic metabolism, increased response
- Decreased renal elimination, increased response
- Decrease BBB, increased CNS effects
What is sensitivity to drugs increased by?
Metabolic disturbance
- Fever
- Dehydration
- Acidosis
What issues are there with medication use in adolescence?
- Major changes in hormone secretion, growth and behaviour
- Major changes in bodyweight
- Non-compliance
- Suicide attempts
- Illicit drug use
- Legal drugs use including smoking, alcohol, anabolic steroids and solvent abuse
Why are trials not done on children?
- Society wants to spare children from potential risks involved in research
- Even well designed trials not totally risk free
- Children may be harmed if they are given medications that are inadequately studied
How can ADRs be reported?
Yellow Card Scheme
- Online
- Using forms found in leaflets
- Calling the hotline
