Cystic Fibrosis Flashcards
Cystic Fibrosis – The Basics
- Incidence: 1 in 3,000
- Autosomal ___ genetic disease
- Average life expectancy is 61
- not just a pediatric disease
recessive
The Basic Problem
- CF is caused by a mutation in a gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein
- The gene is located on chromosome ___
- 2000 + CFTR mutations have been
identified - Most common mutation is ___ del
- ___ mucus
- 7
- F508
- dehydrates
Newborn Screen
- Blood spot obtained from the
infant - Used to test for a variety of diseases including CF
- Immunoreactive ___ (IRT)
- Positive test not diagnostic (Further testing required for diagnosis)
- Earlier diagnosis and treatment of CF has increased patient weight and decreased hospitalizations
- trypsinogen
Diagnosis of CF
One or more sign/symptom + evidence of CFTR dysfunction
Sweat ___ test
- Pilocarpine iontophoresis
- > 60 mEq/L
Genetic testing
___ function
- Stool fat quantitation
- Quantitation of trypsin activity
- chloride
- Pancreatic
Kalydeco
Generic name: ___
Class: cyctic fibrosis transmembrane conductanjce regulator ___
- age ≥ ___ months
- take with ___ foods
- ___ q3 months for 1 year, then yearly
- ___ exam - baseline and yealy (peds)
- Dose adjustment for hepaticimpairment
- CYP __ substrate (DDI &Food)
- Approved for responsive mutations
- ivacaftor
- potentiator
- 1
- fatty
- LFTs
- eye
- 3A
Orkambi ®
Generic: ___ / ___
- Age ≥ __ years
- F508del ___
- Take with ___ foods
- ___ / ___ / ___ q3month for 1 year and then yearly
- ___ exam baseline and then yearly – pediatrics
- Dose adjust in hepatic impairment
- ___ druginteraction!
- Lumacaftor CYP3A strong___
- Ivacaftor CYP3A___
- Side effect of chest tightness and SOB with initiation in some patients
- ivacaftor/lumacaftor
- 1
- homozygous
- fatty
- AST/ALT/Bil
- eye
- Birth Control
- inducer
- substrate
Symdeko
Generic: ___ / ___
- Age ≥ ___ years
- Take with ___ foods
- ___ / ___ / ___ q3month for 1 year and then yearly
- ___ exam baseline and yearly - pediatrics
- Dose adjustment for liver disease
- Ivacaftor CYP3A ___
- Approved for F508del/F508del or people with a ___ mutation
- tezacaftor/ivacaftor
- 6
- fatty
- AST/ALT/Bil
- eye
- substrate
- responsive
Trikafta
generic: ___ / ___ / ___
- age ≥ ___ years
- Take with fatty foods
- ___ / ___ / ___ / ___ Phose qmonth for 6 months and then q3 months for 12 additional months and thenyearly
- ___ exam baseline and yearly -pediatrics
- Dose adjustment for liverdisease
- Ivacaftor CYP __ substrate
- Approved for patients with at least one F508del or one of the other responsive mutations
- If miss orange tablet dose by more than __ hours take orange tablets when remember and ___ evening blue tablet
- Elexacaftor/tezacaftor/ivacaftor
- 2
- fatty
- AST/ALT/Bil/Alk
- eye
- 3A
- 6, skip
Alyftrek
Generic: ___ / ___ / ___
- ___ a day
- Efficacy non inferior toTrikafta
- Take with ___ foods
- AST/ALT/Bil/Alk Phose qmonth for 6 months and then q3 months for 12 additional months and thenyearly
- Eye exam baseline and yearly -pediatrics
- Ivacaftor CYP3A substrate
- Approved for if one F508del or another ___ mutation
- Vanzacaftor/Tezacaftor/ Deutivacaftor
- once
- fatty
- responsive
CF-Lung Disease
- Cause of ~ ___ % of CF deaths
- Due to CFTR dysfunction CF patients have ___ mucus
- This mucus is hard to clear and creates a good environment for bacteria to grow
- Respiratory ___ are common
- 85%
- thickened
- exacerbations
Airway Clearance
Recommended for all CF patients
No method proven better than another
Method based on patient
- Manual airway clearance techniques (P&PD)
- Therapy Vest
- Flutter, acapella
- Huff coughing
- Meta neb
Maintenance Lung Treatment
Dornase alfa
MOA: Cleaves the extracellular DNA from expended ___ and other inflammatory cells in the CF mucus, thus reducing ___ and promoting clearance
- Nebulized solution
- Generally well tolerated but $$$
- Recommended for daily use in CF patients ≥ 6 years old; Can use in select cases < 6 years old
- neutrophils
- viscosity
Maintenance Lung Treatment
Hypertonic Saline
MOA: Exact MOA unclear
Proposed MOA: NaCl in the airway creates an osmotic gradient. This osmotic gradient draws ___ into the airway
- helps to reduce mucus thickness
Hypertonic saline 7% 4 mL nebulized BID
Can reduce the percent of saline if intolerance occurs (3% or 3.5%)
Recommended in all CF patients ≥ ___ years; Can also use in select cases in patients < 6 years old
- water
- 6
Maintenance Lung Treatment
Inhaled ___ (Bronchitol)
MOA: Exact MOA unclear
Proposed MOA: Draws water into the airways to hydrate the mucus
- Approved ___ years and older
- Dry powder inhaler – 400 mg (10 capsules) inhaled twice a day
- Requires ___ test before use
- Alternative to hypertonic saline
Side effects: main one ___ , hemoptysis
- Administer ___ 5-15 min before use
Mannitol
- 18
- tolerance
- bronchospasm
- albuterol
Anti-inflammatory
___ :
- MOA: Immunomodulating effects
- May not be tolerated due to __ side effects – dose can be reduced
- Recommended in patients with chronic ___
Ibuprofen
MOA: anti-inflammatory NSAID
- Not well tolerated due to GI side effects
- Azithromycin
- GI
- pseudomonas
Not Recommended Therapies
ICS
- Asthma symptoms
- Not recommended by current guidelines
- Flovent, Asmanex, etc.
Leukotriene modifiers
- Asthma symptoms
- Not recommended by current guidelines
- ___
Oral ___
- Not recommended by current guidelines
- Montelukast
- corticosteriods
Bronchodilators
___ :
MOA: Short acting beta agonist
- Used to open up airways prior to airway ___ therapy and to decrease bronchoconstriction prior to inhaled ___ ___
- Theoretically increases cilliary beating
- Dosing: Inhaler or nebulized scheduled or prn
Albuterol
- clearance
- hypertonic saline
CF Exacerbation
Not well defined
Typical clinical features (7)
Cover past and current bacteria – the big players
Increased cough
- Increased sputum production
- Shortness of breath
- Chest pain
- Loss of appetite
- Loss of weight
- Decreased lung function
Antibiotics: Empiric IV therapy
MRSA (only single coverage needed) example (5)
MSSA (only single coverage needed) ___ , ___ , coverage by anti-pseudomonal beta lactam
MRSA
- bactrim, clinadmycin, vancomycin, tetracycline, linezolid
MSSA
- cefazolin, unasyn
Pseudomonas for IV Therapy
Double coverage
Two different MOA
- ___ , ___ , ____ , ___ , or ___ with aminoglycoside (tobra, amikacin)
- ___ no longer recommended
- If history of pseudomonas typically cover even if doesn’t grow in current culture
- zosyn, imipenem-cilastin, ceftazidime, meropenem, cefepime
- Gentamicin
Inhaled Antibiotics - Tobramycin
Tobramycin (TOBI)
Dose: 300 mg IH BID
- Recommended for initial ___ eradication – One __ day course
- Suppression therapy in 28 days cycle for patients with ___ pseudomonas
- Administration time 15-20 minutes
Tobramycin (TOBI Podhaler)
- Dose: 112 mg = 4 capsules
= Inh BID
- pseudomonas
- 28
- chronic
Inhaled Antibiotics - Aztreonam
___ (Cayston)
- Dose: 75 mg IH TID eflow® nebulizer
- Used in patient with chronic ___
- Patients that can’t tolerate ___
- Can be used in off months
Treatment time: 5 minutes per treatment X 3 = 15 minutes per day
Cleaning time: 15 minutes per day (depending on number of hand sets)
- Administration time 2-3 minutes
- ___ pretreatment
- Extensive ___ required
- Aztreonam
- pseudomonas
- tobramycin
- Bronchodilator
- cleaning
Why Nebulization?
- Delivery of the drug to the site of infection
- Reduced systemic exposure
- Decreased risk of systemic side effects
- Route allows for ___ administration of antipseudomonal antibiotics without IV
- Ability to get ___ concentrations of the drug to the site
- chronic
- higher
Pancreas
Exocrine insufficiency 85%
- Mucus ___ exocrine ducts
- Decreased enzymes (3) and ___ output
- blocks
- amylase, lipase, protease,
- HCO3
