Exam 3: Cystic Fibrosis Flashcards
What mutation causes cystic fibrosis?
Mutation in gene encoding for CFTR protein
Most common mutation: F508del
What is the incidence of cystic fibrosis?
1 in 3000
What lab value is being tested in newborn screens for CF?
Immunoreactive trypsinogen (IRT)
-this is a measure of pancreatic function, if it is high then the card will get run for a panel of genetics
How do we diagnose cystic fibrosis?
One or more sign/symptom + Evidence of CFTR dysfunction
Sweat chloride test
-measure chloride in sweat
Genetic Testing
Pancreatic function
What result on a sweat chloride test indicates cystic fibrosis?
> 60 mEq/L
What is a Class I Mutation in CF?
CFTR protein not made at all
-Chloride transportation does not occur at all
-we have no modulators for this class
What is a Class II Mutation in CF?
Little CFTR protein reaches the membrane
-CFTR reaching the membrane does not transport chloride properly
What is a Class III Mutation in CF?
Normal number of CFTR proteins at the membrane
Proteins do not open due to a gating mutation (gate is stuck shut)
What is a Class IV Mutation in CF?
Normal number of CFTR proteins at the membrane
Some of the CFTR can transport chloride but not all
What is a Class V mutation in CF?
Reduced number of CFTR proteins at the membrane but the ones that are there function correctly
-High turnover of proteins leads to less
What class of drug is Ivacaftor?
CFTR potentiator
-works for Class 3 and 4 mutations
At what age can Ivacaftor be given?
> /= 1 month
What are the important things to remember for Ivacaftor administration?
Take with fatty foods
LFTs q3 months for 1 year and then yearly
Eye exam
Dose adjustment for hepatic impairment
CYP3A substrate
What is the requirement to be able to take Orkambi (ivacaftor/lumacaftor)?
F508del homozygous
What additional monitoring parameter does Orkambi (ivacaftor/lumacaftor) have?
AST/ ALT/ Bil q 3 months for 1 year and then yearly
What are 2 important considerations with Orkambi (ivacaftor/lumacaftor)?
Birth control drug interaction *** (decreases effectiveness)
CYP3A strong inducer
What effect does Orkambi (ivacaftor/lumacaftor) have in lung function?
Most patients feel the same
-Stabilizes lung function with only slightly increased function
Who is Symdeko (tezacaftor/ivacaftor) approved for?
F508del/F508del
Age >/= 6 years
What is the blockbuster new CF drug?
Trikafta
(Elexacaftor/Tezacaftor/Ivacaftor)
Who is Trikafta approved for?
Age >/= 2 years
Approved for anyone with at least 1 F508del
If someone misses an orange tablet of Trikafta by more then six hours, what should be done?
Take the orange tablets when they remember and skip the blue evening tablet
(because the blue tablets only contain ivacaftor)
What affect does Trikafta have on lung function?
Greatly improves it
-people feel better
Who is Alyftrek (Vanzacaftor/Tezacaftor/Deutivacaftor) approved for?
Anyone with one F508del
(same efficacy as Trikafta)
How do we monitor Alyftrek?
AST/ALT/Bil/Alk Phos:
q month for 6 months
Q3 months for 12 additional months
yearly
How does Dornase alfa work in maintenance lung treatment?
Cleaves the extracellular DNA from expelled inflammatory cells in the CF mucus which reduces viscosity and promotes clearance
How does Hypertonic Saline function as a maintenance lung treatment?
Increases water in the airway which thins mucus
-Nebulized
What is the main side effect of Inhaled Mannitol use for maintenance lung treatment?
Bronchospasm
-May need albuterol beforehand
What are the main considerations when using inhaled mannitol for maintenance lung treatment?
Dry powder inhaler
**Requires tolerance test before use
Acts as an alternative to hypertonic saline
**Causes bronchospasm and may require albuterol administration 5-15min before
Who is azithromycin anti-inflammatory treatment recommended for?
CF patients with chronic pseudomonas
*would consider in patients without it
What are important points to azithromycin anti-inflammatory use?
MOA: immunomodulating effect
Use MWF
GI side effects
When using ibuprofen for anti-inflammatory therapy, what is the goal level range?
> 50mcg/ml and <100mcg/ml
What drugs are not recommended for use in CF?
Inhaled corticosteroids
Leukotriene modifiers (montelukast)
Oral corticosteroids
Bronchodilators (albuterol, ipratropium)
What is FEVI?
The volume of air a person can blow out in one minute
When we treat CF exacerbations, what do we need to cover?
Both past and current bacteria
What do we use for MRSA coverage?
Bactrim
Clindamycin
Vancomycin
Tetracycline
Linezolid
What do we use for MSSA coverage?
Cefazolin
Unasyn (amp + sulbactam)
Anti-pseudomonal beta lactam
What do we use for Pseudomonas IV Therapy?
Double Coverage
Pick one:
-Piperacillin-Tazobactam
-Imipenem-Cilastatin
-Ceftazidime
-Meropenem
-Cefepime
Use with:
-Aminoglycoside (tobramycin, amikacin)
*do not use gentamycin
When do we need to cover pseudomonas?
If it grows in culture OR if there is a history of it
How are the kinetics if beta-lactams altered in CF?
Increased clearance
-need high doses
If a patient has chronic pseudomonas (tried to irradicate it multiple times but it will not go away) what do we use to treat them?
Inhaled Tobramycin
*note that it is also recommended for initial tobramycin eradication
Inhaled Aztreonam
How is the pancreas affected in CF?
Exocrine insufficiency
-Mucus obstructs exocrine ducts
-Have decreased enzymes
What is the typical dosing of pancreatic enzymes?
500-2500 units of lipase/kg per meal
*typically start with 1000
*do not exceed 10,000 units of lipase/kg per day
How do we adjust pancreatic enzymes?
Number of stools per day
Fat content of stools
Growth/weight
What vitamins should we monitor?
Vitamins: D, A, E, K
What is the goal vitamin D level?
> 30
*supplement with cholecalciferol (Vit D3)
