Cystic Fibrosis

Ivacaftor brand name

Kalydeco

Ivacaftor (Kalydeco) MOA

enhances Cl^- conductance by increasing the channel opening probability

Ivacaftor (Kalydeco) does not work in patients with what?

F508 deletions (bc do not have CTFR membrane)

Lumacaftor/Ivacaftor brand name

Orkambi

Lumacaftor/Ivacaftor (Orkambi) MOA

acts as a chaperone to get more CFTR channel to the membrane

Elexacaftor/Tezacaftor/Ivacaftor Brand Name

Trikafta

Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) MOA

• Elexacaftor & Tezacaftor act as chaperones to get more CFTR channel to the membrane

• Ivacaftor helps it work once it is there

Consequence of Cystic fibrosis and problem associated with it

Can develop DM secondary to cystic fibrosis, but it can be hard to manage as time to peak absorption is altered d/t delayed gastric emptying

Complication that causes morbidity and mortality in CF

infection (chronic bacterial infection in the airway)

first line inhaled ABX

tobramycin and aztreonam

T/F: we recommend long term use of oral ABX to treat infection in airways

False - d/t risk of resistance

preferred disease modifying therapy

triple therapy (trikafta)

azithromycin role in CF tx

anti-inflammatory

only solution for end stage lung disease

lung transplantation

Where would small particles like bacteria get trapped in ?

the mucus layer of the bronchi → cleared by cilia beat

where would small particles like viruses get trapped in?

in the alveoli → cleared via phagocytosis from macrophages

layers of mucus layer

• gel layer → mainly just mucus

• sol layer → mainly cilia (beat to move mucus)

Explain the cause of CF

CFTR mutation causes defective chloride channels in cells, leading to thick and sticky mucus.

classic cystic fibrosis

no CFTR function

nonclassic cystic fibrosis

have at least one copy of mutant gene → partial function of CFTR

difference in clinical presentation between classic and nonclassic cystic fibrosis

nonclassic would usually show no signs of maldigestion since some pancreatic exocrine function is preserved

CFTR

transports chloride ions across apical membranes of epithelial cells

which gene mutation would result in no production of CFTR/ improper wrapper (leading it to be ineffective)

delta F508

Describe respiratory management for CF

1. Bronchodilators: SABA to open the airways → 2 puffs prior to tx 2-4x a day

2. Hypertonic Saline: draws water out of the cells into the airway, helping to thin mucus and improve clearance

3. Dornase Alpha: cleaves DNA (dead cells) to reduce mucus viscosity

4. Percussion: to facilitate movement of mucus

5. Inhaled ABX: such as aztreonam and tobramycin to target pulmonary infections

What vitamins need to be supplemented?

ADEK

BMI goal for age 2-20 years

> 50th percentile

When to use PPI in CF?

if pt has GERD and/or if on pancreatic enzyme that is not DR

Explain why pts with CF usually have malabsorption

due to pancreatic insufficiency, which results from thick mucus blocking the release of digestive enzymes. This leads to poor digestion and absorption of nutrients.

What needs to be assessed frequently ?

vitamin D and mineral