Cystic Fibrosis 1- MJ Flashcards Preview

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Flashcards in Cystic Fibrosis 1- MJ Deck (50):

Is Cystic Fibrosis (CF) autosomal dominant or recessive?

Autosomal Recessive


What are the 2 main organ systems that are affected by cystic fibrosis?

  1. Lungs (chronic bacterial infection of airways that is later in onset)
  2. Pancreas (Pancreatitis)


What membrane protein is affected in Cystic fibrosis and what does this protein normally do?

  • CFTR membrane protein
  • Transports chloride ions into the extracellular space, which allows Na ions to follow 
  • Ions go into the mucus resulting in higher conc. of electrolytes outside the cell, causing water to leave the cell---> Making mucus thinner


What happens when the CFTR gene is mutated in Cystic Fibrosis?

  • Ions (Na and Cl) can't be transported across the membrane--> higher electrolyte conc. inside cell and water stays there
  • --> Mucus gets thicker (due to less influx of water)
  • leads to: obstruction, infection and inflammation


 long arm chromosome 7 and CFTR gene:

Which specific mutation most commonly results in Cystic Fibrosis? 

88% are caused by delta F508


Class I mutations of CFTR (defective protein production) acount for what %?



Which class of CFTR mutations includes the delta F508 mutation (accounts for 88% of the dz causing alleles in the US)? 

Class II mutations: defective protein processing



Which CFTR mutation is the most common class III mutation in caucasion populations?


("gating mutation"- impairs the regulated opening of the ion channel formed by CFTR)


Are class III CFTR mutations considered:

  • defective protein processing
  • defective protein production
  • reduced # of active CFTR
  •  defective conduction
  • defective regulation

Defective regulation


Are class IV CFTR mutations considered:

  • defective protein processing
  • defective protein production
  • reduced # of active CFTR
  •  defective conduction
  • defective regulation

Defective conduction


Are class IV CFTR mutations considered:

  • defective protein processing
  • defective protein production
  • reduced # of active CFTR
  •  defective conduction
  • defective regulation

Reduced # of active CFTR


Which CFTR mutation has the following:

  • Reduced trafficking
  • CFTR is mis-processed in the ER, leading to an absence of functional protein at the cell membrane

delta F508


Which CFTR mutation?

  • Reduced gating
  • CFTR protein reaches the cell membrane, but once there is unstable



What are the 2 goals of treatment of Cystic Fibrosis?

1. *Slow/stop the progression of the dz

2. *Allow for normal growth and development


What are the 5 approaches to care of Cystic Fibrosis?

  1. *Good nutrition
  2. *Pancreatic enzymes and vitamin supplementation
  3. *Airway clearance and anti-inflammatory therapies
  4. *Antipseudomonal agents
  5. *Recognize altered pharmacokinetics


What are the 11 possible pulmonary treatments of CF? (in general)

1. Chest phsiotherapy

2. Abx (Tobramycin, Aztreonam)

3. Pancreatic enzyme supplements

4. Multivitamins (including fat-soluble vitamins)

5. Anti-obstructives

6. Anti-inflammatory

7. CFTR modulators

8. Vaccinations and Palivizumab

9. Supplemental Oxygen

10. BiPAP

11. Lung transplant 



Which 2 possible abx can be used as pulmonary tx for CF?




Which 4 anti-obstructives can be used to tx CF?

  1. Dornase alpha (rhDNase)
  2. Hypertonic saline
  3. Inhaled N-acetylcysteine
  4. Bronchodilators (Beta-2 agonists, anticholinergics, Theophylline)



(BAT= B2 agonist, antichol, theoph)


What 3 bronchodilators can be used to tx CF?

Beta-2 agonist






Which 2 anti-inflammatory meds can be used to tx CF?

1. Macrolides- Azithromycin

2. Ibuprofen


Which 3 CFTR modulators can be used to tx CF?

1. Ivacaftor

2. Lumacaftor

3. Tezacaftor


"LIT" modulators 


Which 3 vaccinations are recommended for CF?

1. Influenza vaccine

2. Pneumococcal vaccine 

3. RSV- Palivizumab


What 3 things make up chest physiotherapy?

1. Postural drainage

2. Chest percussion (w/ cupped hand)

3. Vibration technique devices


Recommended sequence of clearance therapy or "pulmonary toilet" regimen:

Therapies are recommended for individuals > ___ years and are administered concurrently with ______  therapy

>6 y/o

Percussion therapy


Recommended sequence of clearance therapy or "pulmonary toilet" regimen:

  • In order for respiratory physiotherapy to be more effective, what 4 things should be done prior? 

  1. Bronchodilator (Albuterol opens up airways and prevents bronchospasm)
  2. Hypertonic saline (hydrates mucus, facilitates mucociliary function)
  3. Dormase alfa (Enzyme results in decreased viscosity of mucus)
  4. Aerosolized abx (Aztreonam, tobramycin)--> indicated based on severity of lung dz, given after percussion therapy




Why is Theophylline infrequently used as an anti-obstructive bronchodilator?

  • Lack of proven efficacy
  • narrow therapeutic margin
  • GI sxs
  • Tachycardia


What are 2 anticholinergic options that are anti-obstructive bronchodilators?

1. Ipatropium (short acting- helpful w/ acute administered)

2. Tiotropium (long acting- no significant improvement--> NO VALUE, don't use in CF)


Why are anti-obstructive inhaled hypertonic saline administered to CF patients?

To Hydrate mucus*

(draws H2O from airway to re-establish the aqueous surface layer that is deficient)


What is the hallmark of CF?

  • presence of abundant, purulent airway secretions composed primarily of highly polymerized DNA
  • Produces a viscous mucous


(this is red on slide)


The hallmark of CF is presence of abundant, purulent airway secretions composed primarily of highly polymerized DNA.

What is the principal source of this DNA?

The nuclei of degenerating neutrophils


A hallmark of CF is the production of a viscous mucus- 

This contributes to decreased what?

Decreased mucociliary transport and persistent infections


The enzyme mucolytic agent, Dornase alpha (rhDNase) does what?

*selectively cleaves DNA*


What 3 things does the enzyme mucolytic agent, Dornase alpha result in?

1. Reduces mucous viscosity

2. Airflow in lungs improved

3. Risk of bacterial infection may be decreased


What is the main con of Dornase alpha?

VERY expensive (~15,000+/year)


What are 11 ADEs of Dornase alpha?

  1.  CP
  2.  Fever*
  3.  Rash*
  4. dyspepsia*
  5. conjunctivitis*
  6. Laryngitis*
  7.  Pharyngitis*
  8.  Rhinitis*
  9.  dyspnea
  10.  Voice alteration


T/F: Albuterol, hypertonic saline and dornase alfa are all inhaled when used to tx CF?



T/F: chronic treatment w/ oral abx to control infection is encouraged in patients w/ CF?


chronic tx w/ oral abx is NOT encouraged

(benefits have not outweighed the probs assoc. w/ abx resistance)


Although chronic tx w/ oral abx to control infection in patients with CF is not encouraged, which 4 abx are exceptions to this?

1. Azithromycin (oral)- can be anti-inflammatory

2. Nebulized tobramycin

3. Nebulized Aztreonam

4. Inhaled colistin (2nd line, off label in US)


Why did CF patients used to die young?

because we didn't have anti-pseudomonal abx


Which micro-organism

isolated from respiratory secretions of pts w/ CF is most prominent?

Staph aureus


(2nd most prominent is Pseudomonas aeruginosa)


Benefits of macrolides (Azithromycin) may be due to what 2 properties?

1. anti-inflammatory properties* (this is specific to Azithromycin)

2. antibacterial properties*


Macrolides are unable to kill which bacteria?

Instead, what does it do?


-*reduces the ability of pseudomonas to produce biofilms*


*Macrolides suppress the excessive _______ response in patients w/ CF*



In cystic fibrosis children >6 y/o, w/ clinical evidence of airway inflammation, is Azithromycin given daily or 3x a week?

3x a week


Nebulized Tobramycin does what 2 things in patients w/ CF

1. *improves lung function*

2. *Reduces acute pulmonary exacerbations chronically infected w/ P. aeruginosa*


What is the MOA of Nebulized tobramycin?

*Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits, resulting in a defective bacterial cell membrane*


T/F: CF patients can be on Nebulized Tobramycin daily for life?


pt should be given Nebulized Tobramycin for 28 days, alternating w/ 28 days off treatment*


What are the 8 main ADEs from inhaled tobramycin?

(the ones highlighted in red on the slide)

1. Sputum discoloration

2. Rales

3. Wheezing

4. Voice alteration

5. cough (powder for inhalation)

6. abnormal taste (powder for inhalation)

7. eosinophilia

8. Tinnitus


"WERC STatic TV"


Inhaled Aztreonam is which type of antibiotic?

A monobactam (beta-lactam) abx w/ antipseudomonal activity*

(Monobactam structure makes cross-allergenicity w/ other B-lactams unlikely)


What is the mechanism of inhaled Aztreonam

*inhibits bacterial cell wall synthesis*