Cystic Fibrosis Flashcards
What is cystic fibrosis?
autosomal recessive disease
-two copies of the gene must be mutated for the person to be affected
What causes cystic fibrosis?
mutations in the CFTR gene
-the most common mutation is F508del
What is the role of CFTR?
regulates chloride ion across apical membranes
-airways, GIT, pancreas, kidney, sweat glands, and male reproductive glands
What does dysfunction of CFTR result in?
disruption of:
-chloride secretion
-sodium reabsorption
-water transport
mutations in CFTR impact composition of secretions and mucus
-results in thick mucous and secretions, which cause the manifestations of CF
What are the typical phenotypes of CF?
lung disease
pancreatic insufficiency
nutrient malabsorption
liver issues
male infertility
Describe the pathophysiology of CF.
lack of functional CFTR protein affects water balance in mucous
-decreased water component, which causes thick and sticky secretions
secretions obstruct ducts of various organs and small airways on the lungs
leads to chronic infections and/or inflammation
What is the impact of the thick secretions on the lungs?
thick lung secretions are hard to clear and leads to bacterial colonization
What are the lungs of a CF patient typically colonized with?
Pseudomonas aeruginosa
Staph aureus
H. influenzae
Stenotrophomonas maltophilia
Burkholderia cepacian
What is a key complication in CF?
pulmonary exacerbation
-increase in respiratory symptoms with systemic symptoms (malaise, anorexia, wt. loss)
What are the pulmonary symptoms seen in CF?
chronic and persistent, productive cough
-purulent and/or blood in sputum
dyspnea, wheezing, chest pain
What is done to monitor the lung function of a CF patient?
routine PFTs
-FEV1
What causes the gastrointestinal complications of CF?
result of thick secretions in GIT and causing obstructions
What are the many GI symptoms that can be seen in CF?
GERD
meconium ileus
intussusception
SIBO
constipation
rectal prolapse
pancreatic insufficiency
decreased absorption of fat-soluble vitamins (ADEK)
When does pancreatic insufficiency typically present in a CF patient?
present from birth in most patients
What does pancreatic insufficiency cause?
decreased volume of pancreatic secretions in ducts
-causes destruction of pancreas bc secretions are retained
leads to decreased absorption of lipids and fat-soluble vits
-steatorrhea, malnutrition, osteoporosis
What are the long-term complications of pancreatic insufficiency?
chronic pancreatitis
glucose intolerance
CF-related diabetes (pancreatic scarring)
What has become a more common complication of CF?
CFRD
-patients are living longer
How does CF cause infertility?
CFTR mutation causes a congenital absence of vas deferens
-greater than 95% male infertility due to absent or normal vas deferens
Can CF impact female fertility?
females have decrease fertility due to thick cervical mucus
What impact can CF have on the nasal cavity?
polyps in nose
What do nasal polyps predispose a CF patient to?
chronic sinusitis
What are the goals of therapy for CF?
maintain lung function as much as possible, ongoing
maintain adequate nutrition, ongoing
maintain QoL
What are the principles of CF pharmacotherapy?
CF pts should be followed and managed by a multidisciplinary team that specialize in CF care
medications are given lifelong
-monitor for AE and adherence
adherence is key - esp. inhaled therapies
-check adherence and inhaler technique q3-6mo or if worsening clinical status
What is the goal of the pulmonary therapies in CF?
increase airway clearance
-long term: slow progression of declining FEV1 and prevent lung transplant
What is key with the administration of pulmonary therapies in CF?
the administration order
What is the correct administration order of the pulmonary therapies in CF?
bronchodilator
hypertonic saline
dornase alfa
physical airway clearance
inhaled antibiotics
inhaled corticosteroids
Which CF patients are indicated for pulmonary therapies?
all CF patients 6 years and older
-shown to improve FEV1, QoL, and decrease exacerbations
Which bronchodilators are used in CF?
short-acting medications
-salbutamol, terbutaline, ipratropium
What is the use of bronchodilators in CF?
decrease the bronchospasm associated with the other inhaled therapies (hypertonic saline and antibiotics)
Which asthma drugs are not routinely recommended in CF?
long-acting bronchodilators
inhaled corticosteroids
montelukast
How is hypertonic saline administered?
nebules
-requires a nebulizing machine for administration
What is the use of hypertonic saline in CF?
mucolytic: increase mucous clearance from airways by thinning out secretions
-more water retained due to high concentration of saline
-reduced viscosity and improved mucus rheology
What strength of hypertonic saline is used for CF?
usually start with 7% but can decrease to 3% if cannot tolerate
What are the adverse effects of hypertonic saline?
coughing
sore throat
wheeze
bronchospasm
What is the use of dornase alfa in CF?
recombinant human deoxyribonuclease that cleaves DNA
-decrease mucous viscosity and decrease inflammation
How is dornase alfa administered?
nebules
True or false: you can mix dornase alfa with other medications in the nebulizer
false
Which inhaled antibiotics are used in CF?
IV injectable liquids that are nebulized:
-levofloxacin, aztreonam, colistimethate
tobramycin (different formulations):
-nebule, Tobi-podhaler, IV injection
What is the usual inhaled antibiotic regimen for CF?
28 days on, 28 days off cycle
-help prevent resistance
Why do most CF patients require pancreatic enzyme replacement therapy?
pancreas is unable to secrete the necessary digestive enzymes to break down lipids
-give exogenous lipase to break down fats and enhance vitamin and mineral uptake
What is the dose of pancreatic enzyme for a CF patient?
doses vary, depending on:
-fat in each meal
-number of meals/snacks per day
-can also be weight-based
True or false: the pancreatic enzyme products are all interchangeable
false
-delayed release, regular release, minimicrospheres for pediatric administration
-many types of products with various lipase units
What are the adverse effects of pancreatic enzymes?
bloating, flatus, pain, loose stools
steatorrhea (MCT oil may help)
dyspepsia
Why are fat-soluble vitamins given to CF patients?
vitamin replacement to counter decreased absorption
Which vitamin product is used in CF?
separate OTC products can be used if nutritional requirements are being met
-but very high doses may be required
MVW Complete Formulation
-lipid-based vitamin product, special formulation
-Special Access Programme
True or false: CFTR modulators are not disease-modifying therapies
false
they are disease-modifying therapies
Which CF patients are CFTR modulators used in?
patients with specific mutations
-partially restore CFTR function in these patients
-patients must have specific mutations and be managed by a CF-specialized physician
When should CFTR modulators be initiated in CF patients?
at the youngest age possible
What are examples of CFTR modulators?
ivacaftor (Kalydeco)
lumacaftor/ivacaftor (Orkambi)
tezacaftor/ivacaftor (Symdeko)
elexcaftor/tezacaftor/ivacaftor (Trikafta)
Differentiate the two MOAs of Trikafta.
corrector:
-helps to fix the flaws in the CFTR protein so that it can form the right shape and traffic to the cell surface
potentiator:
-binds to the defective protein at the cell surface and opens the chloride channel and holds it open so chloride ions can flow through
Which drugs in Trikafta are potentiators and which are correctors?
potentiator: ivacaftor
corrector: elexacaftor, tezacaftor
How should Trikafta be taken?
must be taken with a fat containing food
-might see pts with “fat chasers” as part of their nutrition regimen
Which CF patients is Trikafta approved for?
patients 2 years and older
Which dosage forms does Trikafta come as?
granules and tablets
What are the adverse effects of Trikafta?
elevated LFTs
behavioral/psychiatric changes
cataracts
What are the drug interactions of Trikafta?
many with 3A4 inhibitors and inducers
What are some monitoring parameters for Trikafta?
routine liver enzyme monitoring
ophthalmological exam
Describe the efficacy of Trikafta.
significantly increases FEV1 after 8 wks vs placebo (adults)
increased evidence of sustained FEV1 improvements when used for greater than 6 months
evidence of improvement in lung function trajectory
What might occur for some patients on Trikafta with guidance from a CF team?
some patients may decrease their inhaled airway regimens
What are some other therapies that might be used in CF patients?
GERD and CFRD: treated similarly as non-CF populations
-insulin for CFRD
azithromycin:
-chronic use considered for pts with bacterial colonization (S. aureus and H. influenzae)
-not for prophylaxis but for potential anti-inflammatory
high-dose ibuprofen:
-slow the loss of lung function
-plasma concentrations required
increased nutritional needs:
-high-calorie, high-protein diet
-GT feeding when necessary
What is a CF exacerbation?
significant and sustained change from baseline in respiratory symptoms, pulmonary function or CXR
How are CF exacerbations managed?
minimum of 2 weeks IV antibiotic therapy
-inhaled antibiotics are stopped
Which antibiotics are used for a CF exacerbation when the patient has no previous culture?
piperacillin/tazobactam or ceftazidime with IV tobramycin
-coverage for most CF pathogens AND double-coverage of P.aeruginosa
What are the PK changes in CF patients?
extent and/or speed of oral absorption may be delayed (F unaffected)
-due to gut and pancreas changes
-decreased GI motility and absorption
distribution changes
-pts more likely to be leaner and shorter than avg
-hypoalbuminemia
enhanced clearance of medications
-increased free fractions of drugs
