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MP421 > PAEDIATRIC CANCER > Flashcards

PAEDIATRIC CANCER Flashcards

1
Q

most common childhood cancers

A
  • leukaemia
  • brain and spinal cord
  • lymphomas
  • soft tissue sarcomas
  • neuroblastoma
  • renal tumours
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2
Q

leukaemia causes and risk factors

A

radiation
infections
chemical exposure
previous chemotherapy (mother)
genetic conditions
race
maternal smoking

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3
Q

hyperdiploid

A

a cell that has too many copies of chromosomes

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4
Q

children with hyperdiploid cancer

A
  • generally good prognosis
  • respond very well to chemotherapy
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5
Q

molecular pathology of leukaemia - too many chromosomes

A

about 20% to 25% of children with ALL have more than 50 copies of chromosomes per cell

typically more copies of chromosomes 4, 11 and 17 inside the leukemic cell

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6
Q

hypodiploid

A
  • too few chromosomes
  • less than 44 copies
  • prognosis not as optimistic as hyperdiploid
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7
Q

molecular pathology of leukaemia - chromosomal translocation

A

inside leukaemic cells, part of a chromosome can separate itself and attach to other unrelated chromosomes, producing new chromosomes that express genes in different ways

when chromosomes spontaneously rearrange themselves this way - translocation

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8
Q

problems with chromosomal translocation in children with ALL

A

problems arise when the translocation produces a new gene that instructs the cell to do things it normally wouldn’t (like divide uncontrollably)

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9
Q

most frequent translocation that occurs inside leukaemic cells in children 2-9 years old

A
  • when parts of chromosome 12 and 21 fuse together
  • this translocation represents about 25% of all childhood ALL cases, there are too many B-cell lymphoblasts in the blood and bone marrow
  • also possible to find cells with chromosome 9 and 22 translocated, also called philadelphia chromosome positive, more common in children over 10
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10
Q

long-term morbidities following paediatric ALL treatment

A
  • secondary cancers
  • cardiovascular diseases
  • hepatic dysfunction
  • peripheral neuropathy
  • infertility/hormonal disturbance
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11
Q

difference between treating adult and children cancers

A

ADME
faster absorption and faster elimination in children
paediatric medication errors - dose and safety

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12
Q

why are most drugs for children administered orally

A
  • easier to swallow
  • cheaper to manufacture
  • less painful than injection
  • more convenient to administer
  • less traumatic for carer
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13
Q

the degree of drug absorption through gut wall depends on many factors which differ between adults and children, this includes:

A
  • pH of environment in stomach or gut
  • volume of acidic gastric fluids
  • rate of stomach emptying and rate of gut motility
  • gut microbiome
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14
Q

getting the correct dose into the children

A
  • often put in foodstuffs (do the properties of food alter drug characteristics)
  • does the child eat/drink it all
  • taste masking
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15
Q

potential administration routes in children

A

mucosal
rectal
skin patch
intramuscular

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16
Q

mucosal drug administration in children

A

bypasses first-pass metabolism
i.e. midazolam or lolly (fentanyl)
BUT EXPENSIVE

17
Q

rectal drug administration in children

A

rich blood supply near the arteries
absorption by this route in children is variable long lag time to adsorption

BUT UNCOMFORTABLE FOR CHILD AND CARER - TRAUMATIC

18
Q

skin patch drug administration in children

A

fentanyl
care in children as skin thickness and blood flow highly variable

but: drug leaks long time after patch removed

19
Q

intramuscular drug administration in children

A

causes pain
lose trust of child
distressing

very good bioavailability BUT avoided due to pain and trauma - especially if repeat administrations required

20
Q

absorption in children

A
  • gastric pH higher (less acidic)
  • gastric emptying slowed in under 1-year-olds
  • gastric volume is smaller
  • reduced bile acids and bile flow
  • pancreatic enzymes lower
21
Q

drug factors in drug distribution

A

mostly depend on whether drug crosses membranes and similar to absorption (different in children)

22
Q

patient factors in drug distribution

A
  • differences between adults and children in drug distribution because of body composition and protein binding
  • other physiological factors such as neuromuscular junction, muscle and fat content, different proteins etc.
23
Q

metabolism

A
  • metabolism of drugs is dependent on the liver and its blood flow
  • hepatic blood flow reduced in neonates and infants
  • enzyme systems involved in metabolism very different in varying ages
  • renal efficiency in neonates is decreased
24
Q

childhood obesity

A
  • increasing yearly
  • affects protein binding, blood flow rate, increased tissue volume and perfusion
  • traditionally use weight-based dosing - often don’t choose correct body size metric
25
Q

biggest issue in paediatrics

A

FORMULATIONS AND TASTE

26
Q

other issues in managing childhood illness

A
  • access - lack of child-appropriate formulations, excipients not child-friendly, marketed for adults
  • risk to companies - children are still developing, risk of further abnormalities
27
Q

clinical trials for paediatrics

A
  • need to be minimally invasive
  • few blood samples and pooled data
  • non-invasive
  • ethics

MP421 (12 decks)

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