3- Cystic Fibrosis Flashcards
What is CF
Autosomal recessive disorder on chromosome 7
Where do gene mutations occur
MC: delta F508
MC in caucasians: G551D
Also common, R117H
What are the classes of mutations
I: No protein production
II: Defect in protein processing (d F508)
III: “gating” mutation, defective regulation (G551D)
IV: Defective conduction
V: less stable/active CFTR proteins (d F508)
Goals of CF treatment are to
slow or stop progression of disease
allow for normal growth and development
Summary of CF available treatments
Chest Physiotherapy Antibiotics Pancreatic Enzyme Replacement Therapy Multivitamins (w/ ADEK) Anti-obstructive Anti-inflammatories CFTR modulators Vaccines and Pavilizumab (supplemental O2, BiPAP, lung transplant)
What is involved in chest physiotherapy
postural drainage
chest percussion (cupping of hand)
vibration devices
What is Dornase-Alpha
anti-obstructive that cleaves DNA in mucus secretions to reduce viscosity (thickness)
What are toxicities of Dornase-Alpha
fever pharyngitis rhinitis rash dyspepsia conjunctivitis laryngitis
What is my story for Dornase-Alpha
I travel to Dorn (GoT) to CLEAVE the dna and watch the thin mucus spill.
On my journey I developed a fever and a rash. When I cleaved the soldier’s bodies, the thin mucus got in my eyes, nose, and mouth (conjunctivitis, rhinitis, laryngitis/pharyngitis)
I was so sickened by this that I developed indigestion (dyspepsia)
What is a hallmark of CF
abundant and purulent airway secretions made of polymerized DNA from dead PMN (viscous)
How does hypertonic saline work
draws water from airway to re-establish aqueous surface layer (deficient in CF) AKA hydrates mucus
What abx can be used chronically in CF patients
Tobramycin (aminoglycoside) or Aztreonam (monobactam)
- They are both aerosolized and have anti-PSEUDO properties
- Both need to be used on 28 day cycles. Can alternate them if needed
- *only use if benefit>risk
Do macrocodes kill pseudomonas
NO- but Azithromycin reduces ability to form biofilm so it is more susceptible to destruction
-Azithromycin also anti-inflammatory!
What are S/E of Aztreonam
fever, cough, rash
B-Lactam
What are S/E of Tobramycin
discolored sputum, abnormal taste
rales, wheezing, altered voice, cough
eosinophilia
tinnitus
What are other benefits of Tobramycin
improves lung function nx reduces acute exacerbations
What anti-obstructive bronchodilators can be used to treat CF
SABA/SAMA (albuterol, ipratropium)
Theophylline is not used as much because of it’s side effects
What is inhaled N-acetylcysteine
an anti-obstructive that can be used
Recommended treatment sequence for CF is
bronchodilators
hypertonic saline
dornase alpha
aerosolized antibiotics
What are the anti-inflammatories that can be used in CF
Azithromycin (macrolide)
Ibuprofen
What are the MC pathogens in respiratory secretions of CF patients
<25: Staph Aureus
25+: Pseudomonas Aureginosa
How does Ibuprofen benefit CF patients
reversibly inhibits COX 1/2 (AKA decreased prostaglandins)
-also an anti-pyretic and analgesic
What are Ibuprofen toxicities
Edema/fluid retention HE epigastric pain, GI bleed Tinnitus **can use high dose if <18 y/o with FEV1 >60%
What is PERT
admin of micro encapsulates pancreatic enzymes (lipase, amylase, protease) due to 85% of pts having pancreatic insufficiency
*Dose calculated based on lipase
What are pancreatic enzyme ADE
ulcers of oral mucosa (take with food and rinse after admin) Fibrosing colonopathy (inflammation and strictures) with excessive dose
What does a multivitamin with A, D, E, and K need to be administered
Pancreatic insufficiency and liver disease can cause fat malabsorption
What is Ivacaftor
CFTR modulator that improves gating of surface proteins (mainly G551D), potentiating chloride ion transport (improved Na/H2O absorption/secretion in tissues- lung&GI)
S/E of Ivacaftor are
*Hyperglycemia, increased transaminases HA Abd pain naspharyngitis arthralgia
What is Tezacaftor/Ivacaftor (Symdeko)
Teza moves defective CFTR protein to the correct place on cell surface (Ivacaftor still improved gating)–
Take with fat containing food!
**Approved for those 12+ y/o with 2 delta F508 mutations
Side effects of Symdeko include
same as Ivacaftor, + sinus congestion, dizziness, cataracts
What must you monitor with Symdeko
ALT and AST; prior to starting Tx, every 3 mo. of first year, and yearly after
When should you discontinue Tezacaftor/Ivacaftor
If ALT or AST >5x UL, or, >3x UL with bilirubin >2x UL
What is Ivacaftor/Lumacaftor
Luma partially corrects CFTR misfiling of delta F508 mutation (Iva still improves gating)
- *approved in those with 2 debts F508 mutations
- Improves lung function and reduces exacerbations
- Improves BMI
What CF mutation represents the largest group
2 copies of the delta F508 gene mutation
What vaccines do CF patients need
Flu (6+ mo)
Pneumococcal
Palivizumab
What is Palivizumab
monoclonal antibody to RSV (resp. syncitical virus)
-given in <24 mo.
What are CF GI treatments
ppi (omeprazole) which blocks the H/K/ATP-ase pump in gastric parietal cells so H+ is not secreted
Why give a ppi?
GERD is 8x more common in CF because tummies have less mucus to protect against acid
PPI toxicities include
Diarrhea, acid regurg, constipation
Back pain, weakness, cough
Who gets oxygen therapy
progressive CF with worsening hypoxia
Who gets BiPAP (non-inavsive positive pressure vent)
advanced CF with hypercapnia
Who gets a lung transplant
FEV1 <30%
Increasing exacerbations needing ABX
Recurrent PTX
Recurrent hemoptysis
What is Ursodeoxycholic acid (UDCA)
gallstone dissolution agent that reduces cholesterol secretion from liver and reabsorption by intestines= less cholesterol in bile and bile stones
*In CF bile can back up and obstruct gallbladder
Side effects of UDCA are
Alopecia
Leukopenia
Thrombocytopenia
Increased SrCr
