week 8 Flashcards
what is cystic fibrosis
Autosomal recessive condition
Abnormally sticky mucus, lungs, liver, GI, sweat, pancrease
waht causes CF
defective CFTR (cystic fibrosis transmembrane conduance regulator protein
waht does CFTR do
regulates chloride reabsorption so also NA through ENaC but in CF not reabsorbed
CFTR in CF
reduced CI secretion dn increased NA reabsorbtion so increases passive water reabsorption to mucus left sicky as not as much water and surface layer dehydrated
CLass 1 CF
16.4%)
Premature stop codons, mRNA generated but unstable so not translated- no protein made at all
Class II CF
(80%)
p.Phe508del- protein folds differently- is degraded as tries to go through ER- not very much or no protein at cell surface
Class III CF
(3.9%)
Through ER and golgi but does not open or close very well or at all
Class IV CF
(3.3%)
Gets to cell memraben but deosnt conduct chloride ions very well
Class V CF
3%)
Missense or splice- not very much, does work though
Class VI CF
Less stable- works and get there but degraded at surface quickly
waht do Potentiators do
Increase activity of defective CFTR at cell surface- gating or conductance- helping open and close (Class 3 and 4)
what do correctors do
Overcome defective protein process- chaperone to surface- increase ampunt of CFTR prtein at cell surface
(calss 1,2,5,6)
waht do production correctors do
read through stop codons during translation
ivacaftor brand name
Kaleydeco
what did ivacaftor on tis own treat
type 3 mutations (limited patient impact)
what is Orkambi
lumacaftor and ivacaftor- treats type II
effect of Orkambi
Reduced pulmonary exacerbations, increased BMI and increased FEV1
slow down lng fucntion decline by up to 42%
function of Tezacaftor and ivacaftor alternative
Texacaftor does not increase meatbolism of ivacaftor like lumacaftor does
ivacaftor method of action
Potentiator- erscue epithelia function
ivacaftor effect
10% increase in lung function -2.8 kg weigh gain- 50% decreased lung exacerbations
lumacaftor method of action
Corrector- targets this protein and increase number that are trafficked to surface
porduction correctors target what type of mutation
Class I mutations
Ataluren mode of action
interacts with ribosome and reads through stop codons
Utilitarian ethics-
best for majority
Code of conduct-
doing duty
Virtue
how does a decent persona ct Autonomy Beneficience Non-maleficience Justice
members of Independent committee
Chair At least 2 lay members Hleath and social care professionals Care providors and commissioners Technical experts
Stratification
separation of different groups for which medicines theya re given
ICER
Icnremental- extra
Costs- how much
Effectiveness- what dow e get in QALYS
Ratio- cost per QALY
QALY
length of lfie and quality of life, amount weight by Qol
