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Systems: Paediatrics AB > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What are differences in neonates and children’s responses to drugs due to?

A

Altered pharmacokinetics and pharmacodynamics

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2
Q

What is the safe and effective use of drugs used in children complicated by?

A
  • A lack of acute dosage data
  • A lack of appropriate formulations allowing accurate dosage and delivery
  • Difficulty in detecting ADRs
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3
Q

How can neonates be affected by their mother’s medications?

A
  • In the postnatal period may arise from in utero exposure by transplacental transfer
  • Through breast feeding
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4
Q

What should you consult before prescribing in children?

A

BNFc

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5
Q

What information should parents and children be provided with when prescribing drugs?

A

Information about the disease, treatment and dosage regimen

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6
Q

What must happen before a drug become available to the public

A

Must obtain a license to show it is safe, effective and of high quality

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7
Q

Why can we not use results from trials on adults for children?

A
  • Pharmacokinetic differences between adults and children
  • Altered pharmacodynamics responses
  • Effects on growth and development
  • Different specific pathologies
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8
Q

What are off-label medicines?

A

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

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9
Q

How can medications be used off-label

A
  • 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
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10
Q

How common is off-label use in children?

A

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

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11
Q

What does off-label use increase the rate of?

A

ADRs including death

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12
Q

Why are neonates and infants more sensitive to drugs than adults?

A

Organ system immaturity

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13
Q

Preterm or premature

A

Less than 36 week gestation age

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14
Q

Term new-born (neonate)

A

0 days until 27 days old

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15
Q

Infant

A

28 days until 23 months old

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16
Q

Child

A

2 years until 11 years old

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17
Q

Adolescent

A

12 years until 16-18 years old

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18
Q

What occurs during the phase of physiological immaturity in the early post-natal period?

A
  • 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
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19
Q

What physiological changes occur in infancy?

A

Body weight gain and body water composition change rapidly as does the ratio of bodyweight or surface area to organ size and function.

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20
Q

What issues are there with toddlers and medication?

A
  • Stage associated with minor illnesses which leads to multiple short courses of therapy
  • Problems with compliance
21
Q

How does a young child handle medicine?

A
  • Enhanced metabolism and excretion

- Clearance can change significantly during a single dose regimen.

22
Q

Why is drug metabolism affected in adolescence?

A
  • 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
23
Q

Why can off-licence medications be used in children without data from trials?

A

Most commonly used drugs have a wide therapeutic index

24
Q

Give examples of drugs types which can be very toxic?

A
  • Digoxin
  • SSRIs
  • Anti-epileptic drugs
  • Cytotoxics
25
Q

How may drugs be administered?

A
  • Oral
  • Parenteral
  • Topical
  • Rectal
26
Q

How are drugs administered by the oral route affected in children?

A
  • 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.
27
Q

How are drugs administered percutaneously affected in children?

A

Enhanced in infants and children specially with damaged skin or an occlusive dressing

28
Q

How are drugs administered rectally affected in children?

A
  • 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.
29
Q

How is delivery affected in IV administered drugs in children?

A

Delay or uncertain delivery

30
Q

What can affect drug distribution?

A
  • Body composition

- Plasma protein binding

31
Q

How does extracellular fluid volume vary with age?

A
  • New-born 45%
  • 1 year old 25%
  • Adults 20-25%
32
Q

How does total body water vary with age?

A
  • New-born 75-92%

- Adults 50-60%

33
Q

How does fat content vary with age?

A
  • Term infants 12%
  • 1 year old 30%
  • Adult 18%
34
Q

How should drugs be given in children to achieve the correct plasma concentration?

A
  • 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
35
Q

How is plasma protein binding affected in the neonate?

A

Reduced leading to greater unbound/active drug

36
Q

Why are infants especially sensitive to drugs that cause CNS toxicity?

A
  • BBB is not fully developed at birth

- Drugs and other chemicals have relatively easy access to the CNS

37
Q

Why do drugs take longer to reach steady state in neonates?

A
  • 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
38
Q

Why is hepatic metabolism very slow in the neonatal period?

A

Due to immaturity of drug metabolising enzymes

39
Q

How is hepatic metabolism affected in the neonatal period?

A
  • 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
40
Q

Why do children 1-8 need higher doses of anti-epileptics than adults?

A

Hepatic metabolism is more rapid and t1/2 is shorter

41
Q

What does renal excretion show with age?

A

Progressive maturation

42
Q

When are adult values for renal excretion achieved?

A

3-6 months and tubular function by 12 months

43
Q

How is t1/2 life affected by neonatal excretion?

A

Prolonged

44
Q

What are the main differences to infant pharmacokinetics?

A
  • 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
45
Q

What is sensitivity to drugs increased by?

A

Metabolic disturbance

  • Fever
  • Dehydration
  • Acidosis
46
Q

What issues are there with medication use in adolescence?

A
  • 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
47
Q

Why are trials not done on children?

A
  • 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
48
Q

How can ADRs be reported?

A

Yellow Card Scheme

  • Online
  • Using forms found in leaflets
  • Calling the hotline

Systems: Paediatrics AB (31 decks)

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