Cystic Fibrosis Flashcards
Transmission of Cystic Fibrosis?
autosomal recessive
most common life limiting genetic disorder in white population
life span ~41
Genetic abnormality in CF?
long arm of chromosome 7
88% delta F508
Mutations of CFTR (cystic fibrosis transmembrane conductance)
Class I: defective protein production
Class II: Defective protein processing (protein not properly folded)
Class III: defective regulation (gets to channel but doesn’t work well)
Class IV: defective conductance
Class V: reduced number of active CFTR
Pathophys of CF?
2 defective CFTR genes >
defective CFTR protein >
abn Cl permeability altered ionic transport >
decreased water content in airway surface liquid >
mucus obstruction >
inflammation and scarring >
progressive loss of lung func.
Classic features of CF?
chronic sinusitis, severe chronic bi infx of airways, pancreatic exocrine insufficiency, meconium illeus at birth , sweat chloride value usually 90-110, obstructive azoospermia
Approach to care for CF?
good nutrition
pancreatic enzymes and vitamin supplementation
airway clearance and anti-inflammatory therapies
antipseudomonal agents
Pulmonary tx for CF?
chest physiotherapy, abx, pancreatic enzyme sup., multivitamins, antiobstructives, anti-inflammatory, CFTR modulators, vaccinations, supplemental O2, BiPAP, lung transplant
What is the recommended sequence of clearance therapy for CF (pulmonary toilet) regimen?
~concurrently with percussion therapy
- Bronchodilator (Albuterol)
- Hypertonic Saline
- Dornase alfa (pulmozyme)
- Aerosolized abx ( Aztreonam) indicated based on severity of lung disease and sputum cultures
Dornase alfa MOA?
enzyme cleave EC DNA, results in decreased viscosity of mucus
- airway in the lungs is improved
- risk of bacterial infection may be decreased
$$$
Effect of hypertonic saline?
administered to hydrate mucus –> draws water from the airway to re-establish the aqueous surface layer that is deficient in CF
What is the hallmark of CF?
presence of abundant, purulent airway secretions composed primarily of highly polymerized DNA
ADE of dornase alpha?
fever, rash, pharyngitis, rhinitis, dyspepsia, conjunctivitis, laryngitis
Should CF pts be treated with abx chronically to control infection?
NO
but there is an exceptions if using for anti-inflammatory properties:
-Azithromycin, Nebulized tobramycin, nebulized aztreonam
Most common bacteria in respiratory secretions of CF pts?
s. aureus
How does Azithromycin target pseudomonas bacteria?
reduces the ability of pseudomonas to produce biofilms
Effect of nebulized tobramycin?
improves lung func.
reduces acute pulmonary exacerbations chronically infected w/ P. aeruginosa
Nebulized tobramycin MOA?
interferes w/ bacteria protein synthesis by binding to 30S and 50S ribosomal subunits, resulting in a defective bacterial cell membrane
How is nebulized tobramycin dosed?
BID for 28 days, then alternate with 28 days off tx
ADEs of inhaled tobramycin
sputum discoloration
rales, wheezing, voice alteration
cough, abnormal taste,
eosinophilia
tinnitus
Inhaled Aztreonam drug class? MOA?
Monobactam (beta lactam)- abx with antipseudomonal activity
inhibits bacterial cell wall synthesis
ADEs of inhaled aztreonam?
fever, cough, rash, abd pain, vomiting
Dosage of inhaled aztreonam?
Alternate 28 days on, 28 days off
often Tobramycin and Aztreonam are alternated to provide continuous coverage
Ibuprofen MOA
reversibly inhibits cyclooxygenase 1 and 2 (COX 1 and 2 enzymes)
Who is high dose ibuprofen recommended for?
pts under 18 y/o with FEV1 > 60%
Effects:
-less decline in pulmonary func.
- able to maintain weight and less hospital admission
- freq. blood draws for PK monitoring
Which pts is Ivacattor effective in?
those with G551D gene mutation, ~5% of CF pts
and additional CFTR gene mutations
ADEs of Ivacaftor?
HA, abd pain, nasopharyngitis, hyperglycemia, transaminases increased, arthralgia
ADEs of Ibuprofen
edema, HA, fluid retention, epigastric pain, GI bleed, tinnitus
CFTR Modulator - Ivacattor MOA?
cystic fibrosis transmembrane conductance regulator potentiator
- potentiates epithelial cell chloride ion transport of defective cell surface protein -> allows us to make that protein
- improves regulation of salt and water absorption and secretion in various tissues
what has a major interactive with Ivacaftor?
substrate of CYP3A4
What should you monitor in a pt taking Ivacaftor?
monitor blood glucose and LFTs
What is the drug class of Lumacaftor and Ivacaftor combination (Orkambi)?
cystic fibrosis transmembrane conductance regulator potentiator
Lumacaftor/Ivacaftor combination MOA?
Lumacaftor: partially corrects the CFTR misfolding
Ivacaftor: improves the Cl gating abnormality
Tezacaftor/Ivacaftor (symdeko) - Dose should be reduced in who?
in pts with mod/severe hepatic impairment. When co-administration with drugs that are moderate or strong CYP3A inhibitors
ADEs of Lumacaftor/Ivacaftor?
nasopharyngitis, fatigue, menstrual disease, increased creatine phosphokinase, URI, rhinorrhea
Tezacaftor/Ivacaftor (symdeko) MOA?
Tezacaftor: move the defective CFTR protein to the proper place in the airway surface cell (similar to LUmacaftor)
Ivacaftor: improves the Cl gating abnormality
What is the most common gene mutation in cystic fibrosis?
F508del
Who is Tezacaftor/Ivacaftor approved for?
> 12 y/o with two copies of F508del or those with single copy of certain specified mutations
Tezacaftor/Ivacaftor (symdeko) should be taken with…
fat containing food
ADEs of Tezacaftor/Ivacaftor?
HA, nausea, sinus congestion, dizziness
What should be monitored in pts taking Tezacaftor/Ivacaftor?
ALT/AST every 3 months during first yr, then annually
cataracts
What vaccinations should CF pts receive?
influenza vaccine, pneumococcal vaccine
Palivizumab in children <24mos
When should pt be referred for lung transplant?
- FEV1 < 30% or rapid decline in FEV1 particularly in young female pts
- increasing freq. of exacerbations requiring abx tx
- refractory and or recurrent pneumothorax
- recurrent hemoptysis not controlleld by embolization
ADEs of UCDA?
Alopecia
leukopenia, thrombocytopenia
serum creatinine increased
ADEs of Omeprazole?
Acid regurgitation, constipation, back pain, weakness, cough
ADEs of pancreatic enzyme supplementation?
prolonged contact with oral mucosa may cause ulcers
administer with food, rinse mouth after administration
excessive dose: fibrosing colonopathy, characterized by inflammation and strictures
What vitamins should be supplemented in CF pts?
fat soluble vitamins
A, D, E, K
(pancreatic insufficiency and CF related liver disease lead to fat malabsorption)
Tx for CF related liver disease?
Urosodeoxycholic acid (UCDA)
gallstone dissolution agent
-MOA: reduction of the secretion of cholesterol from the liver and the fractional reabsorption of cholesterol by the intestines
