Cystic Fibrosis etiology
autosomal recessive disease
What is the gene mutation in CF?
Long arm Chromosome 7
What is the gene mutation in Class II, defective protein processing??
F508
What is the gene mutation in Class III, defective regulation?
G551D
List bronchodilators we would use as anti-obstructives
- B-2 agonists- Albuterol
- Theophylline
- Anticholinergics- Ipratropium (short acting) and Tiotroprium (long-acting)
Why do we use hypertonic saline as an anti-obstructives
Hydrates mucous my osmotically pulling water from airway to re-establish the aqueous surface layer that is deficient in CF
what is the hallmark of CF?
Abundant/purulent airway secretions made of polymerized DNA from dead neutrophil
Viscous mucous
What is the MOA of Dornase alpha (rhDNase)
Selectively cleaves DNA in mucous secretions to reduce mucous viscosity
Dornase alpha SEs
- Fever- 32% in pt’s with FVC <40%
- Pharyngitis, rhinitis
- Laryngitis
- Dyspepsia
- Conjunctivitis
- Rash
What is a downside to Dornase alpha?
You can produce antibodies to the medication
What is the most common bacterial organism in kids/younger adults?
S. aureus
What is the most common bacterial organism in adults (25-34 yrs)?
Pseudomonas aeruginosa
What is the main benefit of Macrolides (Azithromycin)
Anti-inflammatory properties
–>Supres excessive inflammatory response
Macrolides (Azithromycin) MOA
Reduces ability of pseudomonas to produce biofilms so other drugs can kill it
Aminoglycosides (nebulizer Tobramycin) application
- Improves lung function
2. Reduces acute pulmonary exacerbations chronically infected with pseudomonas
What is unique about Aminoglycosides (nebulizer Tobramycin) dosing?
Alternate with 28 days of treatment to try and reduce resistance
Aminoglycosides (nebulizer Tobramycin) SEs
- GI: sputum discoloration, abnormal taste
- Respiratory: Rales, wheezes, cough, voice alteration
- Otic: Tinnitus
- Hematologic: Eosinophilia
List the monobactam (beta-lactam)
Inhaled Aztreonam
Inhaled Aztreonam MOA
inhibits bacterial cell wall synthesis
Inhaled Aztreonam application
Abx with antipseudomonal activity
Inhaled Aztreonam SEs
- Fever
- Cough
- Rash
What is unique about Inhaled Aztreonam dosing
for 28 days, then off for 28 days- DO NOT repeat for 28 days after completion
Who we do use HIGH dose ibuprofen in?
<18 y.o. with FEV1 >60%
Ibuprofen SEs
- GI: Epigastric pain, GI bleed
- CV: Edema
- Endocrine: Fluid retention
- Otic: Tinnitus
- CNS: HA
Ivacaftor MOA
Potentiates epithelial cell chloride ion transport of defective (G551D) cell-surface CFTR protein
What does Ivacaftor improve?
Regulation of salt and water absorption and secretion in lung, GI tract, etc
Ivacaftor SEs
- Hyperglycemia-Monitor blood sugars
- Transaminases increased
- HA
- Abdominal pain
- Nasopharyngitis
- Arthralgia
What gene mutation represents the largest group of people with CF? Percentage of people?
F508 gene mutation
88%
What is the combo effect of Lumacaftor/Ivacaftor
- Reduction in pulmonary exacerbations
- Improved lung function
- Increased BMI
What are the concerning SEs of Lumacaftor/Ivacaftor combo therapy?
- Menstrual disease
- Increased creatine phosphokinase
- URI
- Rhinorrhea
- Nasopharyngitis
- Fatigue
When would we need to adjust the dosing of Tezacaftor/Ivacaftor?
If coconmitant use with moderate and strong inhibitors (antifungals)
–>CYP3A interaction
What do we need to monitor with Tezacaftor/Ivacaftor?
ALT and AST
When do we discontinue Tezacaftor/Ivacaftor treatment?
LT or AST >5 x upper limit of normal
What is a major SE of Tezacaftor/Ivacaftor?
Cataracts
List the two vaccines we want to administer to our CF patients
- Influenza- older than 6 mos.
2. Pneumococcal
What is Palivizumab?
Monoclonal antibody against RSV
Kids younger than 24 mos
What FEV1 % would indicate a referral for a lung transplant?
FEV1<30%
What do proton pump inhibitors increase your risk of?
Aspiration pneumonia
What are the SEs of Omeprazole?
- Acid regurgitation
- Constipation
- Back pain
- Weakness
- Cough
What percentage of CF patients will have pancreatic insufficiency in their lifetime?
85%
What are the main pancreatic enzymes?
- Lipase
- Amylase
- Protease
What is the dose calculated by?
According to the Lipase
What are the major ADEs of Pancreatic Enzyme Supplementation
- Oral Mucosa Ulcers with prolonged contact-Administer with food and rinse after
- Fibrosing Colnopathy
Why do we need to add vitamin supplementation in our CF patients?
Fat malabsorption due to:
- Pancreatic insufficiency
- Liver dz’s
What are fat soluble vitamins?
A, D, E & K
What CF-related liver disease is an issue in CF? Why?
Gallstones
Bile can back up and obstruct GB
What can we give our CF patients with Gallstones?
Ursodeoxycholic acid (UCDA) -Gallstone dissolution agent
UCDA ADEs
- Leukopenia
- Thrombocytopenia
- Alopecia
- Increased serum creatinine
