Cystic Fibrosis- Higgins

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What is the most common autosomal recessive disease in the Caucasian population?

idk how imp

Cystic Fibrosis (CF)

Which mutation accounts for up to ~70% of all CFTR mutations?

idk how imp

F508del mutation

What is the risk of having an affected child when both parents are heterozygous carriers of F508del?

idk how imp

25% with EACH pregnancy

What is the genetic inheritance pattern of cystic fibrosis?

a. autosomal dominant

b. autosomal recessive

c. sex-linked on the X chromosome

d. sex-linked on the Y chromosome

idk how imp

b. autosomal recessive.

What is the gold standard test for diagnosing cystic fibrosis?

Other tests?

• GOLD STANDARD: Sweat Chloride Test (Quantitative pilocarpine iontophoresis sweat chloride test)

• others: newborn screening, genetic/carrier testing, clinical evaluation

I would just recognize the gold standard

What sweat chloride concentration is diagnostic for cystic fibrosis?

≥ 60 mmol/L

(note: CFTR-related metabolic syndrome is 30-59 and CF not likely <30)

True or False: cystic fibrosis only affects the lungs.

false—> many other body systems involved

Preventative care and non-pharm for CF include:

• smoke free home

• up to date vaccines

• RSV prophylaxis

• vitamins

• education/ counseling

• shorter exercises

• hand hygiene

• 6-ft rule

• airway clearance techniques

What mucoactive agents are used in CF?

• dornase alfa nebule

• HYPERtonic saline 7% nebule

• mannitol inhaled

  • 2nd line to hypertonic saline

At what age is chronic dornase alfa recommended to improve lung function?

pts. ≥ 6 years old

What inhaled antibiotics are used in CF?

• which is 1st line?

• administer ___ days on and ___ days off.

• Inhaled tobramycin—> 1st line

• Aztreonam lysine—> alternative, or in preg

• colistin

• administer 28 days on and 28 days off

Which pathogens are most commonly isolated in CF respiratory cultures?

• idk how imp… more of an FYI

• Pseudomonas aeruginosa

• Staphylococcus aureus

• MRSA

• Burkholderia cepacia complex

• nontuberculous mycobacteria.

Administration of respiratory medications should go in what order?

1. bronchodilator (opens airway)

2. hypertonic saline (hydrates and improves airway clearance)

3. dornase alfa (thins mucus)

4. airway clearance

5. inhaled abx (abx activity)

What is oral azithromycin used for in CF pts.?

What are the effects?

• ≥6 years w/ chronic infection of P. aeruginosa or positive culture in 6 months or older and continue for 18 months

• effects:

  • antimicrobial

  • anti-inflammatory

Tx for pulmonary exacerbation?

idk how important

• abx

  • IV or inhaled

• increase in airway clearance therapy

Define pancreatic exocrine insufficiency (PI) in CF:

FYI

Obstruction of pancreatic ducts by thick secretions leading to malnutrition and growth failure

Which test is used to screen for pancreatic insufficiency (PI)?

idk how imp

Fecal pancreatic elastase-1 (<100 µg/g indicates PI)

Tx of PI?

Pancreatic enzyme replacement therapy (PERT) —> combo of lipase, protease, and amylase

For PERT:

• max dose?

• WHEN IS IT GIVEN?

• 2,500 lipase units/kg/meal

• given prior to meals/snacks

Why do CF patients require specialized multivitamins?

increased risk of fat-soluble vitamin (A, D, E, K) deficiency

Which form of vitamin D is preferred in CF supplementation?

Vitamin D3 (cholecalciferol)

What is the treatment of choice for cystic fibrosis–related diabetes (CFRD)?

Insulin therapy

For bone disease in CF, what scan is performed and how often?

• DXA scan

• performed annually >8 years

What is the treatment for bone disease in CF?

• DOC?

• 2nd line?

• bisphosphonates

  • oral alendronate—> DOC

• 2nd line- denosumab

Answer the following about bisphosphonates in CF:

• T score or Z score for use

• oral risedronate if >____ years

• duration?

idk how important

• T score >-1 or Z score >-2 use

• oral risedronate if >18 yrs

• duration—> <5 years

CF liver disease is the 3rd leading cause of death.

Which medication displaces toxic bile acids and may delay cirrhosis progression in CF liver disease?

Ursodiol

Administration consideration of Ursodiol include:

do not admin with aluminum-based antacids or bile acid sequestrants—> admin 2 hours after ursodiol

List gastrointestinal complications common in CF aside from pancreatic issues:

• Gastroesophageal reflux disease (GERD)

• distal intestinal obstruction syndrome (DIOS)

• constipation

• fibrosing colonopathy

What class of drugs is first-line for GERD management in CF?

Proton pump inhibitors (PPIs)

FYI note: monitor for pulmonary exacerbation, vit B12 deficiency, hypomagnesemia, and bone health

How is constipation is managed in CF?

osmotic laxatives and assessing PERT dosing

The PHQ-9 for depression and GAD-7 for anxiety are recommended annually for CF patients beginning at what age?

CF patients ≥12 years

FYI: recommended to assess 7-11 years if there are concerns

What class of is considered first-line for CF patients if pharmacotherapy is needed for depression/anxiety?

Selective serotonin reuptake inhibitors (SSRIs)

What are the 3 types of CFTR Modulators?

• correctors

• potentiators

• amplifiers

What is the MOA of CFTR correctors?

List the names of them:

• MOA: increase amount of functional CFTR at the cell surface

• names:

  • lumacaftor

  • tezacaftor

  • elexacaftor

What is the MOA of CFTR potentiators?

List the names of them:

• MOA: keep the channel open to increase the transport of chloride in/out of the cell

• names:

  • ivacaftor

What is the MOA of CFTR amplifiers?

List the names of them:

• MOA: increases the amount of CFTR protein in the cell

• no medications FDA approved

  • pipeline agent: nesolicaftor

Choosing a CFTR modulator:

• delta F508 homozygous pts. ≥6 years of age

• delta F508 homozygous pts. 1-5 years

• delta f508 heterozygous pts. ≥6 years of age

• ≥6 years of age with at least one mutation that is responsive to

• ≥4 months with one of the 97 CF gene mutations drug is responsive to

Sadly must know.

• delta F508 homozygous pts. ≥6 years of age

  • preferred: Elexacaftor/tezacaftor/ivacaftor (Trikafta)

  • alt: ezacaftor/ivacaftor (Symdeko)

• delta F508 homozygous pts. 1-5 years

  • Lumacaftor/ivacaftor (Orkambi)

• delta f508 heterozygous pts. ≥6 years of age

  • Trikafta

• ≥6 years of age with at least one mutation that is responsive to

  • Symdeko or Trikafta

• ≥4 months with one of the 97 CF gene mutations drug is responsive to

  • Ivacaftor (Kalydeco)

Trikafta is the brand name of what combo of CFTR modulators?

Elexacaftor/tezacaftor/ivacaftor

Symdeko is the brand name of what combo of CFTR modulators?

ezacaftor/ivacaftor

Orkambi is the brand name of what combo of CFTR modulators?

Lumacaftor/ivacaftor

Which CFTR modulator was approved for patients unable to tolerate Trikafta?

Vanzacaftor/tezacaftor/deutivacaftor (Alyftrek)

What meal recommendation should accompany CFTR modulator administration?

Take with a high-fat meal

What 2 things should be monitored on all CFTR modulators?

• LFTs

• eye exams

Which CFTR modulator may cause chest discomfort and dyspnea soon after initiation?

Lumacaftor/ivacaftor (Orkambi)

CFTR modulators are substrates of which cytochrome P450 enzyme, leading to many drug interactions?

CYP3A4

Why should corticosteroids be minimized in CF patients?

idk how imp

They contribute to bone loss and further reduce bone mineral density

PRACTICE:

ZL is an 8-year-old White male with cystic fibrosis (heterozygous for F508del). ZL’s parents have decided they want him to have a CFTR modulator. Which of the following appropriate for this patient?

a. Lumacaftor/ivacaftor

b. Elexacaftor/tezacaftor/ivacaftor

c. Tezacaftor/ivacaftor

d. Ivacaftor

b.

What are the initial presenting symptoms of CF?

• meconium ileus (bowel obstruction)

• failure to thrive

• respiratory symptoms

  • productive cough, wheezing, breathing issues

• rectal prolapse