Cystic Fibrosis Flashcards
What mutated gene is most responsible for Cystic Fibrosis?
Autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene
What is the purpose of the CFTR protein?
Regulates chloride ion across apical membranes (environment-facing)
What is the functional effect of CFTR mutation?
Disruption of Cl- secretion, water reabsorption, and water transport
These changes impact the composition of secretions and mucus
What organ systems are affected by CFTR mutations/CF?
- Lung disease
- Pancreatic insufficiency
- Nutrient malabsorption
- Liver issues
- Male infertility
By which mechanism does CF cause organ dysfunction?
Secretions obstruct the ducts on various organs and small airways in the lungs
What is the life expectancy for patients with treated CF?
Average life expectancy is 57 years in patients living in developed countries
What are some lung-specific CF symptoms?
Thick lung secretions are hard to clear (chronic productive cough, dyspnea, chest pain) and leads to bacterial colonization
Lungs are colonized with a number of pathogens (chronic infection)
Key complication in CF is pulmonary exacerbation (increased respiratory sx with systemic sx such as malaise, anorexia, weight loss)
Routine pulmonary function tests are done to track pulmonary function.
What are some GI-specific CF symptoms?
Thick secretions in GIT can cause obstructions
GERD, blocked meconium, blockages, constipation, rectal prolapse
Pancreatic insufficiency
- Decreased absorption of fat-soluble vitamins (responsible for metabolic processes, can cause obesity)
What are some characteristics of pancreatic insufficiency in CF?
Present from birth in most patients
Decreased pancreatic secretions in ducts (decreased absorption of lipids and fat-soluble vitamins)
Long-term complications:
- Chronic pancreatitis
- Glucose intolerance
- CF-related diabetes
What is CF-related diabetes (CFRD)?
More common as patients are living longer
Exact mechanism is unknown, but perhaps due to pancreatic scarring
What are some fertility-specific sx of CF?
CFTR mutations causes congenital absence of vas deferens (>95% male infertility)
Females may have decreased fertility due to thicker cervical mucus (acts as a spermicide)
What are some nasal-specific symptoms of CF?
Nasal polyposis (polyps in nose, predisposed to develop chronic sinusitis)
Treated with nasal rinsing
What are three goals of therapy for CF?
- Maintain function as much as possible, ongoing
- Maintain adequate nutrition, ongoing
- Maintain quality of life
Is there a cure for CF?
No, but we have access to treatments that can slow disease progression
What are some principles for CF treatment?
CF patients are followed and managed by a multi-disciplinary team
Medications are given life-long (monitor adverse effects and adherance)
Adherance is key, especially for inhaled therapies
What is the goal of pulmoary therapies in CF?
- Bronchodilator
- Hypertonic Saline
- Dornase Alfa
- Physical airway clearance (chest physio)
- Inhaled antibiotics (prophylaxis)
- Inhaled corticosteroids (for more progressive patients)
What is the youngest age for CF pulmonary therapies?
6 years and older (may used nebulized therpies in younger children)
What bronchodilators are used in CF?
Salbutamol, terbutaline, ipratropium
Long-acting bronchodilators are not routinely recommended
What is the utility of bronchodilators in CF?
Used to decrease bronchospasms associated with other inhaled therapies (hypertonic saline and antibiotics)
What is the pupose of hypertonic saline in the treatment of CF?
Increase mucous clearance from airways by thinning out secretions
Start with 7%, and can decrease to 3% if cannot tolerate
What are some adverse effects associated with hypertonic saline nebules?
Coughing, sore throat, wheeze, bronchospasm
What is the purpose of dornase alfa in the treatment of CF?
Recombinant human deoxyribonuclease that cleaves DNA (decreases mucous viscosity by eliminating WBCs in mucous and decrease inflammation)
What inhaled antibiotics are used prophylactically for CF?
Tobramycin (most commonly used antibiotic in CF)
Levofloxacin, aztreonam, colistimethate (broad-spectrum antibiotics, concerns about resistance)
What is the utility of pancreatic enzymes in CF treatment?
Used to treat pancreatic insufficiency
Exogenous pancreatic lipase is given to break down fats and enhance vitamin and mineral uptake
What are some adverse effects associated with pancreatic enzymes?
- Bloating, flatus, pain, loose stools
- Steatorrhea
- Dyspepsia (switch to a different formulation)
What is different about CFTR modulators, compared to traditional CF therapies?
They are the only ones that are disease modifying
What is the most common CFTR modulators used to treat CF?
Trikafta and Kalydeco
What is the generic name of the main component of Kalydeco?
Ivacaftor
What are the generic names for the active agents in Trikafta?
Elexcaftor/Tezacaftor/Ivacaftor
What are the two main functions of Trikafta in the treatment of CF?
Corrector (helps fix flaws in CFTR protein so it can form the right shape and function)
ex. Elexcaftor and Tezacaftor
Potentiator (binds to defective protein and allows chloride ions to flow)
ex. Ivacaftor
What are some administration instructions for Trikafta?
Must be taken with a fat containing meal
Approved for patients over 2
CYP3A4 inhibitors and inducers
What is the efficacy of Trikafta?
Significantly reduces FEV1 after 8 weeks of treatment vs. placebo
Sustained FEV1 when used for greater than 6 months
How old does a CF patient need to be to initiate CFTR modulators?
Should be initiated at the youngest age possible, can be younger than 4 years old depending on the agent selected
Review slide 35 for other CF therapies
What is the role of a pharmacist in managing CF drug therapies?
Monitor inhaler technique, adherence, adverse effects, and worsening disease
Ensure patients have drug coverage through EDS, Special Support, and SAIL
What do CF flare-ups present like?
A significant and sustained change from baseline in respiratory sx, pulmonary fxn, or CXR
What is a CF “Tune-Up”?
Patients receive a minimum of 2 weeks of IV antibiotic therapy via central line
ex. Piptaz or ceftazadime
Coverage for most CF pathogens and double coverage of P.aeruginosa
What are some changes in PK in patients with CF?
- Extent or speed of oral absorption is delayed (due to gut & pancreas changes, reduced GI motility)
- Patients are leaner and shorter than the average patient (impact on low Vd drugs)
- Enhanced clearance of drugs due to lower albumin levels caused by pancreatic insufficiency
