Chapter 55. Cystic Fibrosis

What gene is mutated in CF?

• Cystic fibrosis transmembrane conductance regulator (CFTR)

• Leads to abnormal transport of chloride, bicarb, and sodium ions across epithelium

• Leads to thick, viscous secretions that affect lungs, pancreas, liver, and intestines

By what age are the majority of patients diagnosed with CF?

By 2 years

If an initial test is positive for CF, what is the confirmatory test for diagnosis?

Sweat test (chloride sweat test)

Classic symptoms of CF?

• Salty tasting skin

• Poor growth/weight gain

• thick/sticky mucus production

• frequent lung infections

• Coughing/SOB

• Steatorrhea (fatty stools)

• Malnutrition if not treated

Inhaled Medications for CF (In order! It matters.)

1. Inhaled Bronchodilators (e.g. albuterol) - opens airways

2. Hypertonic saline (e.g. HyperSal) - mobilizes mucus

3. Dornase alfa (Pulmozyme) - thins mucus

4. Chest physiotherapy - mobilizes mucus

5. Inhaled antibiotics - controls infection

*oral products, like pancreatic enzyme, azithromycin, can be taken any time

What are the most common infectious disease organisms early in disease?

S. aureus, H. influenzae, Pseudomonas in adolescents and adults

What drug is used for synergy in treating Pseudomonas with 2 IV drugs?

Aminoglycosides (doses tend to be larger than normal)

What is the treatment for patients with chronic pseudomonas?

Inhaled abx; 28 days on and then 28 days off (cycle)

How does Azithromycin work for pseudomonas in CF?

No direct activity against pseudomonas, but disrupts biofilm formation

How is hypertonic saline used?

via nebulizer

Dornase alfa brand name

Pulmozyme; decreases mucus viscosity

Dornase alfa administration notes

• Protect form light

• Store ampules in fridge

• Do not mix with any other drug in nebulizer

Which antibiotic comes as a capsule for inhalation?

Tobramycin (targets pseudomonas)

Inhaled Tobramycin Brand name

TOBI, TOBI Podhaler

Administration notes for Tobramycin

• Doses must be at least 6 hours apart

• Refrigeration recommended for TOBI (can be at room temp for 28 days)

• Room temperature for capsules (TOBI Podhaler); do not swallow caps

• Do not mix w other drugs in nebulizer

Tobramycin side effects

• Ototoxicity, tinnitus

• voice alteration

• mouth and throat pain

Aztreonam (Azactam) side effects

• Allergic rxns (may be severe)

• Bronchospasm

• Fever

• Wheezing

• Cough, chest discomfort

Aztreonam/Azactam administration notes

• Refrigeration recommended; good at room temp for 28 days

• Doses must be at least 4 hours apart

• Do not mix w other drugs in nebulizer

What is the purpose of taking oral Azithromycin (Zithromax) even though it does not target pseudomonas?

Decrease exacerbations

What is commonly given to CF patients to break down fat, starches, and protein?

Pancreatic enzyme products

What medication is harvested from porcine pancreatic glands and contains a combination of lipase, amylasae, and protease?

Pancrelipase; formulated to dissolve in more basic pH of duodenum

What is the dose of pancrelipase based on?

The lipase portion; adjusted every 3-4 days until stools are normalized

What is the MAX dose of pancrelipase for all ages?

≤ 10,000 units/kg/day

Side effects/Warnings of Pancrelipase

• Colonic strictures

• Mucosal irritation

• Abdominal pain, flatulence, nausea

Pancrelipase brand names

Viokace, Creon, Zenpep

Are pancreatic enzyme products (PEPs) interchangeable?

NO

What is the only PEP that is a tablet?

Viokace; must be given with PPI, not enteric coated

*others are capsules

How should PEPs be taken?

• Delayed release capsules may be opened and sprinkled on soft, acidic foods (pH ≤4.5) like applesauce (avoid high pH like dairy)

• Swallow immediately to avoid irritation

• Take before or with all meals and snacks (high fat = higher dose)

- use 50% of meal dose with snacks

• Protect from moisture; dispense in original container (exceptions: some creon strengths and Zenpep). Do. not refrigerate

What medication works by increasing the time the CFTR channels remain open?

Ivacaftor; cannot be used in homozygous F508del (most common mutation)

Which drugs increases the amount of CFTR delivered to cell surface?

Lumacaftor, tezacaftor, elexacaftor

What must be performed prior to starting a CFTR modulator?

Genotypic testing

What is the most common genotypic mutation in the CFTR gene?

homozygous F508del mutation

Counseling for CFTR modulators?

take with high-fat meal

What supplement should patients with CF take?

Vitamins, especially ADEK

What medication will all CF patients likely eventually require?

Insulin