Cystic Fibrosis Flashcards
What is CF? (3)
- Autosomal recessive disease (two copies of the gene must be mutated for the person to be affected)
- CF is caused by mutations in the CF transmembrane conductance regulator gene (CFTR)
- The most common mutation is F508del
What does CFTR do?
Regulates chloride ion across apical membranes
- Airways, GIT, pancreas, kidney, sweat glands, and male reproductive glands
Dysfunction of CFTR results in disruption of: (3)
- Chloride secretion
- Sodium reabsorption
- Water transport
Mutations in CFTR impact the composition of secretions and mucus which results in?
Results in thick mucous and secretions, which cause the manifestations of CF
What to know (very general) about CF genotypes? (3)
- Class I through VI
- Differences in presentation of CFTR and function
- e.g., Class I have no CFTR, but Class IV mutations have impaired chloride conductance and some function
What are some examples of CF phenotype? (5)
- Lung disease
- Pancreatic insufficiency
- Nutrient malabsorption
- Liver issues
- Male infertility
CF affects mostly which race?
Caucasians
What is the pathophysiology of CF? (3)
- Lack of functional CFTR protein affects water balance in mucous
- Decreased water component, which causes thick and sticky secretions - Secretions obstruct the ducts on various organs and small airways on the lungs
- Leads to chronic infection and/or inflammation in many different areas of the body
CF affects the whole body, but what are the 4 major areas we are focusing on?
- Pulmonary
- GI
- Infertility
- Nasal polyps
What is the key complication in CF?
Pulmonary exacerbation
- Thick lung secretions are hard to clear and leads to bacterial colonization
Lungs are typically colonized with: (5)
- Pseudomonas aeruginosa
- Staph. aureus
- H. influenzae
- Stenotrophomonas maltophilia
- Burkholderia cepacian
What are the signs and symptoms in the pulmonary system with CF? (4)
- Chronic and persistent, productive cough
- Purulent and/or blood in sputum - Dyspnea
- Wheezing
- Chest pain
What does a pulmonary exacerbation of CF entail?
Increase in respiratory symptoms with systemic symptoms
- Malaise, anorexia, weight loss
Routine ____ are done to track pulmonary function in CF patients
PFTs
How does CF affect the GI system? (4)
- Result of thick secretions in GIT and causing obstructions
- GERD, meconium ileus, distal intestinal, intussusception, small intestine bacterial overgrowth (SIBO), constipation, rectal prolapse
- Pancreatic insufficiency
- Decreased absorption of fat-soluble vitamins (ADEK)
- Neuropathy, coagulopathy, osteoporosis
What to know about pancreatic insufficiency in CF patients? (4)
- Present from birth in most patients
- Decreased volume of pancreatic secretions in ducts
- Causes destruction of the pancreas because these secretions are retained - Leads to decreased absorption of lipids and fat-soluble vitamins
- Steatorrhea and malnutrition
- Osteoporosis - Long-term complications: chronic pancreatitis, glucose intolerance and CF-related diabetes (CFRD)
What are 2 things to note about CF related diabetes (CFRD)?
- Patients are living longer, so this is a more common complication
- Exact mechanism is unknown, but might be due to pancreatic scarring
How does CF cause infertility in males and females? (3)
- CFTR mutation causes a congenital absence of vas deferens
- Greater than 95% male infertility due to absent or abnormal vas deferens
- Females may also have decreased fertility due to thick cervical mucus
- Acts as a spermicide
Nasal polyps predisposes the person for _______ _________
chronic sinusitis
What are the 3 goals of therapy for CF?
- Maintain lung function as much as possible - ongoing
- Maintain adequate nutrition - ongoing
- Maintain quality of life
What are 3 pharmacotherapy principles to be aware of for CF?
- CF patients should be followed and managed by a multidisciplinary team that specialize in CF care
- Medications are given lifelong
- Monitor for adverse effects and adherence - Adherence is key – especially for inhaled therapies
- Check adherence and inhaled device technique every 3-6 months or if worsening clinical status
The goal of pulmonary therapies is to ________ ______ _________
increase airway clearance
The administration order of the inhaled CF therapies is important. What is that order?
- Bronchodilator –>
- Hypertonic saline (3 or 7%) –>
- Dornase Alfa –>
- Physical airway clearance (chest physio) –>
- Inhaled antibiotics –>
- Inhaled corticosteroids
The pulmonary therapies are indicated in all CF patients _ years and older
6
CF bronchodilator medications include: (3)
- Salbutamol
- Ipratropium
- Terbutaline
(Short-acting medications)
What are short-acting medications used for in CF? What to know about the dosing?
- Used to decrease the bronchospasm associated with the other inhaled therapies (hypertonic saline and antibiotics)
- Same doses as asthma
Long-acting bronchodilators, ICS, montelukast for CF therapy. Yay or nay?
Nay. Not routinely recommended
What is the MOA of hypertonic saline?
Mucolytic: increase mucous clearance from airways by thinning out secretion
- More water retained due to high concentration of saline
- Reduced viscosity and improved mucus rheology (flow)
What are the adverse effects of hypertonic saline? (4)
- Coughing
- Sore throat
- Wheeze
- Bronchospasm
Hypertonic saline requires a _________ _______ for administration
nebulizer machine
What is the MOA of dornase alfa?
Recombinant human deoxyribonuclease that cleaves DNA
* Decrease mucous viscosity and decrease inflammation
What to note about the administration of dornase alfa?
Cannot mix with any other meds in nebulizer
What inhaled antibiotics are used for CF therapy? (4)
IV injectable liquids that are nebulized:
1. Levofloxacin
2. Aztreonam
3. Colistimethate
4. Tobramycin = different formulations (nebule, Tobi-podhaler, IV injection)
In what patients are inhaled antibiotics used (in CF)?
For pts with Pseudomonas aeruginosa on sputum culture
- Can be used for early eradication treatment, chronic suppressive therapy
- Providing high concentration of antibiotic to the airways
What is the usual regimen for inhaled antibiotics (CF)?
28 days on, 28 days off cycle
- Help prevent resistance
What happens with the pancreas in CF?
It is unable to secrete the necessary digestive enzymes to break down lipids
Pancreatic enzymes are given for what purpose?
Initiated in most patients
- Give exogenous lipase to break down fats and enhance vitamin and mineral uptake
Doses of pancreatic enzymes vary depending on: (3)
- Fat in each meal
- Number of meals/snacks per day
- Can also be weight-based
True or False? Pancreatic enzyme products are interchangeable
False
Not interchangeable - delayed release, regular release, minimicrospheres for pediatric administration
What are the ADEs of pancreatic enzymes? (6)
- Bloating
- Flatus
- Pain
- Loose stools
- Steatorrhea (MCT oil may help to control this)
- Dyspepsia
Vitamin ADEK can be supplemented individually, but if you want it all, what is the special formulation you can use?
MVW Complete Formulation
- Lipid-based vitamin product, special formulation
- Available in Canada from Special Access Programme only
What is the MOA of CFTR modulators? (2)
- Disease-modifying therapies
- Partially restore CFTR function in patients with specific mutations
- Patients must have specific mutations and be managed by a CF-specialized physician
- CFTR Modulators should be initiated at the YOUNGEST age possible
-caftor meds are what class?
CFTR modulators
Should know the name of the most common CFTR modulator (brand and generic)
Trikafta
= Elexcaftor/Tezacaftor/Ivacaftor
Corrector or Potentiator?
Elexacaftor =
Tezacaftor =
Ivacaftor =
Elexacaftor = Corrector
Tezacaftor = Corrector
Ivacaftor = Potentiator
What does a corrector do (CFTR modulator)?
Helps to fix the flaws in the CFTR protein so that it can form the right shape and traffic to the cell surface
What does a potentiator do (CFTR modulator)?
Binds to the defective protein at the cell surface and opens the
chloride channel and holds it open so chloride ions can flow through
How must Trikafta be administered?
What age?
Forms?
- Administration: must be taken with a fat containing food
- Might see patients with “fat chasers” as part of their nutrition regimen - Approved for patients 2 years and older
- Available as granules and tablets
What to know about safety for Trikafta? (2)
- Elevated LFTs, behavioural/psychiatric changes, cataracts
- Drug interactions: many with CYP 3A inhibitors and inducers (St. John’s wort, grapefruit juice)
What to monitor when on Trikafta? (2)
- Routine liver enzyme monitoring
- Ophthalmological exam
What to know about efficacy of Trikafta? (3)
- Significantly increases FEV1 after 8 weeks vs. placebo (adults)
- Increased evidence of sustained FEV1 improvements when used for greater than 6 months
- Evidence of improvement in lung function trajectory
What are the “other” therapies for CF? (4)
- GERD and CFRD: treated similarly as non-CF populations
- Insulin for CFRD - Azithromycin
- Chronic use considered for patients 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 the pharmacist’s role in CF? (5)
Monitor:
1. Inhaler technique
2. Adherence
3. Adverse effects
4. Worsening disease
5. Ensure patients have drug coverage
- EDS, Special Support, SAIL program (Cystic Fibrosis Program)
What does a CF exacerbation look like?
Significant and sustained change from baseline in respiratory
symptoms, pulmonary function or CXR
How is a CF exacerbation treated?
Patients receive a minimum of 2 weeks IV antibiotic therapy
* Inhaled antibiotics are stopped
What is the pharmacist’s role in a CF exacerbation? (5)
- Selecting appropriate antimicrobial therapy guided by previous patient cultures
- Therapeutic drug monitoring (AMG)
- Monitoring of adverse effects
- Medication Reconciliation – complex home regimens
- Access to CFTR modulators while in hospital
What antibiotics are used in a CF exacerbation?
No previous cultures: piperacillin/tazobactam or ceftazidime with IV tobramycin
- Coverage for most CF pathogens AND double-coverage of P. aeruginosa
What to know about CF pharmacokinetics? That is, absorption, distribution, and clearance?
- Extent and/or speed of oral absorption may be delayed (bioavailability unaffected)
- Due to gut and pancreas changes
- Decreased GI motility and absorption - Distribution changes
- Patients are more likely to be leaner and shorter than the average patient
- Hypoalbuminemia – changes to protein bound drugs - Enhanced clearance of medications
- Increased free fraction of drugs
