PAEDIATRIC CANCER Flashcards
most common childhood cancers
- leukaemia
- brain and spinal cord
- lymphomas
- soft tissue sarcomas
- neuroblastoma
- renal tumours
leukaemia causes and risk factors
radiation
infections
chemical exposure
previous chemotherapy (mother)
genetic conditions
race
maternal smoking
hyperdiploid
a cell that has too many copies of chromosomes
children with hyperdiploid cancer
- generally good prognosis
- respond very well to chemotherapy
molecular pathology of leukaemia - too many chromosomes
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
hypodiploid
- too few chromosomes
- less than 44 copies
- prognosis not as optimistic as hyperdiploid
molecular pathology of leukaemia - chromosomal translocation
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
problems with chromosomal translocation in children with ALL
problems arise when the translocation produces a new gene that instructs the cell to do things it normally wouldn’t (like divide uncontrollably)
most frequent translocation that occurs inside leukaemic cells in children 2-9 years old
- 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
long-term morbidities following paediatric ALL treatment
- secondary cancers
- cardiovascular diseases
- hepatic dysfunction
- peripheral neuropathy
- infertility/hormonal disturbance
difference between treating adult and children cancers
ADME
faster absorption and faster elimination in children
paediatric medication errors - dose and safety
why are most drugs for children administered orally
- easier to swallow
- cheaper to manufacture
- less painful than injection
- more convenient to administer
- less traumatic for carer
the degree of drug absorption through gut wall depends on many factors which differ between adults and children, this includes:
- pH of environment in stomach or gut
- volume of acidic gastric fluids
- rate of stomach emptying and rate of gut motility
- gut microbiome
getting the correct dose into the children
- often put in foodstuffs (do the properties of food alter drug characteristics)
- does the child eat/drink it all
- taste masking
potential administration routes in children
mucosal
rectal
skin patch
intramuscular
mucosal drug administration in children
bypasses first-pass metabolism
i.e. midazolam or lolly (fentanyl)
BUT EXPENSIVE
rectal drug administration in children
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
skin patch drug administration in children
fentanyl
care in children as skin thickness and blood flow highly variable
but: drug leaks long time after patch removed
intramuscular drug administration in children
causes pain
lose trust of child
distressing
very good bioavailability BUT avoided due to pain and trauma - especially if repeat administrations required
absorption in children
- 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
drug factors in drug distribution
mostly depend on whether drug crosses membranes and similar to absorption (different in children)
patient factors in drug distribution
- 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.
metabolism
- 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
childhood obesity
- 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
biggest issue in paediatrics
FORMULATIONS AND TASTE
other issues in managing childhood illness
- access - lack of child-appropriate formulations, excipients not child-friendly, marketed for adults
- risk to companies - children are still developing, risk of further abnormalities
clinical trials for paediatrics
- need to be minimally invasive
- few blood samples and pooled data
- non-invasive
- ethics
