Cystic fibrosis Flashcards
(17 cards)
Most common reason for mortality in cystic fibrosis
Lung dysfunction & infection
Effects of Cystic fibrosis - 5
Impaired function of organs with secretory function:
- Eccrine sweat glands
- Epididymis & vas deferens (infertility in males)
- Nasal polyps
- Pancreas - reduced enzyme secretion e.g. Insulin
- Digestive system - meconium ileus & obstruction, failure to thrive in new-borns
Cystic fibrosis in men
Can cause infertility & shorter lifespan
Cystic fibrosis screenings - 3
- Immunoreactive trypsinogen (IRT) - Guthrie Test
All new-borns in UK. Trypsinogen made by pancreas & secretion (into gut) impaired in CF is elevated in the blood. - IRT positive (& siblings) screened for most common mutations
- Sweat test: Elevated skin Cl- levels
Below 30 mM – CF unlikely
Above 60 mM – CF likely
Management of nutrition in cystic fibrosis - 2
- Malnutrition is former principal mortality due to pancreatic insufficiency - e.g. lack of pancreatic protease, amylase, lipase.
- Unable to digest foods properly, managed by diet & enzyme supplements.
What supplement is given in cystic fibrosis to aid digestion?
Pancreatin
Why is lung disease a principal cause of mortality in cystic fibrosis - 5
- Chronic infection
- Mucus plugging
- Structural changes
- Massive neutrophil infiltration in airways
- Failure to clear bacteria & dying neutrophils causes Inflammatory DMG to airway tissue (epithelial DMG), reducing lung function
What is the CTFR - 3
- Cystic Fibrosis Transmembrane Conductance Regulator
- Allows Cl, Na & H20 to leave cells into lungs to hydrate the airways.
- The ENaC channel ensures H20 is reabsorbed so overhydration does not occur.
How does CFTR act in cystic fibrosis - 4
- In cystic fibrosis CFTR does not function properly so less Na & H20 exit cells due to less Cl being transported out.
- Causes dehydration of the airways.
- Lack of H20 volume results in sticky viscous mucous forming.
- The mucus is hard for the cilia to clear, providing a growth environment for bacteria.
Why are secondary bacterial infections in cystic fibrosis hard to treat?
Depth & biofilm growth.
Antibiotics used in cystic fibrosis - 4
- Prophylactic floxacillin in infants
- Regular swab or sputum cultures
- Early oral/IV intervention
- Inhaled antibiotics are useful.
What is the main therapy for cystic fibrosis
CFTR Modulators which target the CFTR gene mutations.
The actions of CFTR - 5
- Read through compounds – force through the stop codon e.g. ataluren
- Correctors – overcome folding defects e.g. lumacaftor, tezacaftor
- Potentiators – modulate gating characteristics e.g. ivacaftor
- Amplifiers – enhance amount of function protein e.g. PTI-CH
- Stabilisers – maintain shape & function of protein e.g. cavosonstat
Give 3 examples of CTFR modulator combination therapy?
Orkambi: Corrector & a potentiator
e.g. Lumacaftor + ivacaftor
Symdeko: Corrector & a potentiator
e.g Tezacaftor + ivacaftor
Trikafta® /Kaftrio: 2 correctors & a potentiator
e.g. Elexacaftor + Tezacaftor + Ivacaftor
How is ion transport restored in cystic fibrosis - 2
- Calcium-activated chloride channel (CACC) activators
P2Y2 agonist (denufusol) - ineffective at maintaining lung function. Increases intracellular Ca, activating CaCCs, increasing Cl secretion - Blocking ENaC: e.g. Amiloride
New compounds may be more effective but hyperkalaemia risk
Anti-inflammatory therapy in Cystic fibrosis - 4
- Glucocorticoids:
Inhaled, no proof of a reduction in inflammation
IV (prednisolone) some benefit, but significant S/Es - Macrolides:
Non-antibiotic effect of azithromycin? - High dose ibuprofen
- Brensocatib: Inhibits neutrophil elastase.
Currently Phase II clinical trial
Overview of Cystic fibrosis - 6
- Nutrition management with enzyme supplements
e.g Oral Pancreatic enzyme replacement therapy ‘PERT’ - Pancreatin – protease, amylase, lipase - Antibiotics
- Anti-inflammatory therapies e.g. High dose Ibuprofen + Glucocorticoids
- Mucus hydration – hypertonic saline, mannitol
- Mucus breakdown - DNAse
- CFTR modulators
