Cystic Fibrosis Flashcards
What is cystic fibrosis?
Cystic fibrosis (CF) is an incurable, hereditary disease caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). The mutation causes abnormal transport of chloride, bicarbonate and sodium ions across the epithelium, leading to thick, viscous secretions. The thick mucus affects the lungs, pancreas, liver and intestines, which causes difficulty breathing, lung infections and digestive complications
What is the average life expectancy of someone with cystic fibrosis?
The average life expectancy of a person with CF is 35-40 years with more than 75% of patients being diagnosed by 2 years of age
How is cystic fibrosis diagnosed?
Newborn screening is performed in the US in the first 2-3 days after a baby is born. NBS includes testing for CF and other conditions. If the initial screening identifies a risk of CF, then a sweat chloride test is performed to confirm the diagnosis
What is a sweat test?
The sweat test measures the amount of salt (chloride) in the sweat, which is high in patients with CF
What are the classic symptoms of CF?
The classic symptoms of CF are salty tasty skin, poor growth and poor weight gain, thick and sticky mucus production, frequent lung infections, coughing and shortness of breath. Patients experience obstruction of pancreatic ducts causing steatorrhea (fatty stools) and poor absorption of nutrients. Clubbing of the fingers may be present
What is the goal of therapy for CF?
The primary goals of therapy include preventing/treating lung infections, maintaining adequate nutrition and optimizing quality of life
What medications do CF patients typically receive?
Most patients will receive airway clearance therapies, inhaled antibiotics targeting Pseudomonas aeruginosa and pancreatic enzyme replacement
What is the order for inhaled interventions for CF?
1) Inhaled bronchodilators: opens the airways
2) Hypertonic saline: mobilizes mucus to improve airway clearance
3) Dornase alfa: decreases viscosity of mucus to promote airway clearance
4) Chest physiotherapy: Mobilizes mucus to improve airway clearance
5) Inhaled antibiotics: controls airway infection
What is the importance of inhaled therapies for CF?
Inhaled therapies are the foundations of treatment in CF. The drug is delivered directly to the lungs, resulting in minimal systemic absorption (reducing the risk of toxicity). Although inhaled medications are an effective form of drug delivery, the average patient with CF receives up to 10 doses of inhaled medications daily, which can take 2-3 hours to administer
What are the most common organisms seen early in CF?
The most common organisms seen early in the disease are Staphylococcus aureus and Haemophilus influenzae, followed by Pseudomonas aeruginosa in adolescents and adults
How is acute pulmonary exacerbations characterized?
Acute pulmonary exacerbations are characterized by an increase in cough, sputum production with a change in sputum color (greenish), shortness of breath and a rapid decline in FEV1
What is included in the treatment of acute pulmonary exacerbations?
Treatment often includes an extended course of antibiotics (2-4 weeks) and modalities to increase airway clearance
What medications can be used for infections caused by Pseudomonas aeruginosa?
For infections caused by Pseudomonas aeruginosa, two IV drugs are recommended to provide potential synergy and prevent resistance. These include aminoglycosides, beta-lactams, quinolones and others that cover Pseudomonas aeruginosa
Describe the doses used for treating Pseudomonas in patients with CF.
Doses end to be larger than normal to address altered pharmacokinetics in patients with CF, obtain therapeutic drug concentrations in lung tissue and to overcome reduced susceptibility of the bacteria chronically colonizing the airways
What is recommended for CF patients with chronic Pseudomonas aeruginosa?
Inhaled antibiotics are recommended for patients with chronic Pseudomonas aeruginosa lung infections to reduce the bacterial burden. treatment is cycled with 28 days on therapy, followed by 28 days off
If a patient is given inhaled aztreonam, what is the normal dosing and why is it optimal dosing?
Inhaled aztreonam is dosed TID and should be scheduled as close to every 8 hours as possible. This dosing provides optimal bacterial killing around the clock, while minimizing the time when the antibiotic concentration is low (which can worsen resistance)
How is inhaled tobramycin dosed?
Inhaled tobramycin is dosed every 12 hours and should be scheduled as close to every 12 hours as possible with at least 8 hours in between doses
When can azithromycin be considered for chronic infection of Pseudomonas?
A 6 month trial of oral azithromycin can be considered for patients with chronic infection who are worsening on conventional treatment. Azithromycin has no direct bactericidal activity against Pseudomonas, but disrupts biofilm formation by the bacteria which can improve lung function and decrease exacerbations
What are some examples of inhaled airway clearance therapies?
Bronchodilator, hypertonic saline, dornase alfa (Pulmozyme)
What are some notes about hypertonic saline?
- Hypertonic saline is supplied as small ready-to-use vials that are delivered via a nebulizer
- PulmoSal is buffered to match physiologic pH of airway surface
- Hypertonic saline is a high-alert drug, especially with IV administration
How does Pulmozyme work?
Works by degrading extracellular DNA in the lungs to decrease viscosity of (thin) mucus
What are contraindications of Dornase alfa?
Hypersensitivity to Chinese Hamster Ovary (CHO) products
What are some side effects of Pulmozyme?
Chest pain, fever, rash, rhinitis, laryngitis, voice alteration, throat irritation
What are some notes about Dornase alfa?
- Store ampules in the refrigerator (do not expose to room temperature > 24 hours)
- Protect from light
- Do not mix with any other drug in the nebulizer
What are examples of inhaled antibiotics that target suppression of Pseudomonas?
Tobramycin, Aztreonam, Azactam
What are some side effects of Tobramycin?
Ototoxicity, tinnitus, voice alteration, mouth and throat pain, dizziness, bronchospasm
What are some notes about inhaled tobramycin?
- Give for 28 days, followed by 28 days off cycle
- Dosed every 12 hours, but must be at least 6 hours apart
- TOBI, Bethkis, Kitabis: refrigeration recommended ( can be kept at room temperature up to 28 days); store in foil pouch to protect from light; do not mix with any other drug in the nebulizer
- TOBI Podhaler: store capsules at room temperature in a dry place; use with Podhaler (device dispensed with the capsules); do not swalow capsules
What are some side effects of inhaled aztreonam and azactam?
Allergic reactions (may be severe), bronchospasm, fever, wheezing, cough, chest discomfort
What are some notes about inhaled aztreonam or inhaled azactam?
- Give for 28 days, followed by 28 days off cycle
- Dosed every 8 hours, but must be at least 4 hours apart
- Refrigeration recommended (can be kept at room temperature up to 28 days)
- Do not mix with any other drug ion the nebulizer
- Use with Altera nebulizer system
- Protect from light
What are some side effects of azithromycin in CF?
Tinnitus, nausea, risk of QT prolongation
What is a pancreatic complication from CF?
The thick mucus in CF obstructs pancreatic enzyme flow, resulting in a lack of these enzymes reaching the gastrointestinal tract and malabsorption
What are some manifestations of pancreatic insufficiency?
Frequent, greasy, oily, foul-smelling stools are manifestations of pancreatic insufficiency
What is pancreatic enzyme replacement therapy and why is it necessary?
Most patients with CF need to supplement their diet with pancreatic enzyme products (PEPs) to help break down fat, starches and protein
What is pancrelipase?
Pancrelipase is a natural product harvested from porcine pancreatic glands which contains a combination of lipase, amylase and protease
How are PEPs formulated and dosed?
PEPs are formulated to dissolve in the more basic pH of the duodenum. The dose is individualized for each patient and is based on the lipase component. Once PEP is started, the dose is adjusted every 3-4 days until stools are normalized
What are some warnings of Pancrelipase?
Fibrosing colonopathy advancing to colonic strictures (rare: higher risk with doses > 10,000 lipase units/kg/day), mucosal irritation, hyperuricemia
What are some side effects of Pancrelipase?
Abdominal pain, flatulence, nausea, HA, neck pain
What are some monitoring parameters of Pancrelipase?
Abdominal symptoms, nutritional intake, weight, height (children), stool, fecal fat
What is the purpose of PEP?
Pancreatic enzyme replacement helps patients with CF digest food, maintain weight and improve nutrient absorption
What are commonly used PEP products?
Creon, Viokace and Zenpep
What are some counseling points about pancreatic enzyme products?
- PEP formulations are not interchangeable
- Viokace is the only PEP that is a tablet. It is non-enteric coated and must be given with a PPI
- All other PEPs are capsules
- Take PEPs before or with all meals and snacks. High-fat meals may require high doses
- Protect from moisture; dispense in original container. Do not refrigerate
What are some examples of cystic fibrosis transmembrane conductance regulator (CFTR) modulators?
Ivacaftor (Kalydeco), Lumacaftor/ivacaftor (Orkambi), Texacaftor/ivacaftor (Symdeko), Elexacaftor/texacaftor/ivacaftor (Trikafta)
How does Ivacaftor work?
Ivacaftor works by increasing the time the CFTR channels remain open, which enhances chloride transport activitiy
How does Lumacaftor, Texacaftor and Elexacaftor?
Lumacaftor, tezacaftor and elexacaftor help correct the CFTR folding defect, which increases the amount of CFTR delivered to the cell surface
What is the most common mutation in the CFTR gene?
The most common mutation in the CFTR gene is a homozygous F508 del mutation (two copies of the same allele).
What approved mutation does Ivacaftor treat?
Not approved for use in the homozygous F508del mutation; approved for use in other responsive mutations
What approved mutation does Lumacaftor, Tezacaftor and Elexacaftor?
Approved for use in the homozygous F508del mutation and additional responsive mutations
What are some warnings about CFTR modulators?
Increased LFTs, cataracts in children
What are some notes about CFTR modulators?
- Take with high-fat containing food
- Kalydeco: > 4 months of age
- Orkambi: > 2 years of age
- Symdeko: > 6 years of age
- Trikafta: > 12 years of age
Describe the CFTR modulator drug interactions.
Ivacaftor is a substrate of CYP450 3A4 (major) and should be avoided with strong CYP3A4 inducers. Dosage adjustments may be required when CFTR modulators are used with CYP3A4 inhibitors
What is recommended for the treatment of CF to address the patient’s growth, nutrition, bone health and other CF complications?
- A high-fat and calorically dense diet is recommended to help with nutrition, normal weight and growth, increased energy needs to prolong survival
- Vitamin supplements are required, especially the fat-soluble vitamins A, D, E and K for normal cellular function. Calcium and vitamin D intake/absorption should be monitored to maximize bone health
- Many patients with CF will eventually require insulin for treatment of CF-related diabetes mellitus
- If the patient maintains good health, the chances of qualifying for a transplant are improved
What are some counseling points about TOBI Podhaler?
- Do not swallow capsules
- Use only the provided Podhaler device
- Take doses as close to 12 hours but no less than 6 hours apart
