Cystic Fibrosis

Question 1

Genetic disorder that affects the lungs, pancreas, liver, and intestines, leading to thick, sticky mucus buildup.

Answer 1

Cystic Fibrosis

Question 2

What gene mutation leads to Cystic Fibrosis?

Answer 2

CFTR
- leads to defective Chloride transport

Question 3

Patients with Cystic Fibrosis are most prone to lung infections caused by what bacteria?

Answer 3

Pseudomonas Aeruginosa

Question 4

What are some GI symptoms of Cystic Fibrosis?

Answer 4

Pancreatic Insufficiency
- poor absorption and growth
Steatorrhea

Question 5

What are some non-lung symptoms of Cystic Fibrosis?

Answer 5

Infertility
- especially in males due to absence or obstruction of the vas deferens
Digital Clubbing

Question 6

How are newborns screened for Cystic Fibrosis?

Answer 6

Immunoreactive Trypsinogen (IRT)
- heel stick test

Question 7

How many known mutations are there of the CFTR gene?

Answer 7

Over 2000

Question 8

A Sweat Test for Cystic Fibrosis would be positive if?

Answer 8

Chloride > 60 mmol/L

Question 9

What does Spirometry show in patient with Cystic Fibrosis?

Answer 9

Obstructive Lung Pattern
- ↓ FEV1 and ↓FVC

Question 10

What are some airway clearance techniques used to manage Cystic Fibrosis?

Answer 10

Chest Physiotherapy
High-Frequency Chest Wall Oscillation
Positive Expiratory Pressure Devices

Question 11

What inhaled treatments are used for Cystic Fibrosis?

Answer 11

Bronchodilators = Albuterol
Mucolytics = Dornase alfa
Inhaled ABX
Inhaled Corticosteroids

Question 12

What inhaled ABXs are used for Cystic Fibrosis, especially for Pseudomonas Aeruginosa?

Answer 12

Tobramycin
Aztreonam

Question 13

ABX that interferes with bacterial protein synthesis by bind to the 30S and 50S ribosomal subunits, resulting in a defective bacterial cell membrane.

Answer 13

Tobramycin

Question 14

Who is Tobramycin used for?

Answer 14

Patients 6+ with
P. aeruginosa

Question 15

How is Tobramycin dosed and given?

Answer 15

2x daily for 28 days

Question 16

Adverse Drug Reactions of Tobramycin

Answer 16

Ototoxicity + Nephrotoxicity
Bronchospasm
Productive Cough

Question 17

Do you need to monitor the drug levels of Tobramycin?

Answer 17

No

Question 18

Monobactam that inhibits bacterial cell wall synthesis by binding penicillin-binding proteins (PBPs) which inhibit peptidoglycan synthesis in bacterial cell walls.

Answer 18

Aztreonam

Question 19

Who is Aztreonam used for?

Answer 19

Patients 6+ with
P. aeruginosa

Question 20

How is Aztreonam dosed and given?

Answer 20

3x daily for 28 days

Question 21

Special recommendation for Aztreonam

Answer 21

Pre-Treat with Bronchodilator
- do not mix together

Question 22

Common regimens of oral and IV ABX for systemic treatment of Cystic Fibrosis

Answer 22

Beta Lactams
Aminoglycosides
Fluoroquinolones

Question 23

Medication that selectively cleaves DNA, thus reducing mucous viscosity.

Answer 23

Dornase Alfa

Question 24

How is Dornase Alfa given?

Answer 24

Nebulization
- 1x daily

Question 25

Precautions of Dornase Alfa

Answer 25

if FVC < 40% - it did not reduce risk of infections that require ABX

Question 26

Adverse Drug Reactions of Dornase Alfa

Answer 26

Cough Pharyngitis Rhinitis Chest Pain Voice Disorder

Question 27

ABX Therapy for Cystic Fibrosis typically requires how many medications?

Answer 27

2+ for P. aeruginosa

Question 28

Considerations for Cystic Fibrosis Patients

Answer 28

Contact Precautions Clean + Disinfect Nebulizers Stay up to date on Vaccinations!

Question 29

What inhibits digestive enzymes from being released from the Pancreas in patients with Cystic Fibrosis?

Answer 29

Mucus Buildup - aim for BMI at or above 50th percentile - for adults Female = 22+ BMI Male = 23+ BMI

Question 30

What is a common endocrine complication of Cystic Fibrosis?

Answer 30

Diabetes

Question 31

Nutritional support medications formulated to: Dissolve in the more basic pH of duodenum to break down fats, protein, and starch.

Answer 31

Pancreatic Enzyme Replacement Therapy (PERT): Combo Lipase, Amylase, Protease.

Question 32

What are some examples of PERT Medications?

Answer 32

Creon Pancreaze

Question 33

Recommended Dose of PERT

Answer 33

Based on Weight - Lipase 500-2500 units/kg/meal - MUST be taken with meal or Snack (1/2 Dose)

Question 34

High Doses of PERT (6000+ units/kg/meal) are associated with what?

Answer 34

Colonic Stricture

Question 35

Adverse Drugs Reactions of PERT

Answer 35

Headache Abdominal Pain Lymphadenopathy Nasal Congestion

Question 36

Medications that target the underlying defect in the CFTR protein, improving Chloride transport in Epithelial Cells

Answer 36

CFTR Modulators

Question 37

What are the Classes of CFTR Modulators?

Answer 37

Correctors - Ivacaftor + Lumacaftor Potentiators - Ivacaftor Combination Therapies - Trikafta = (Ivacaftor + Lumacaftor + Tezacaftor)

Question 38

CFTR Modulator that helps the CFTR protein fold correctly and reach the cell surface.

Answer 38

Correctors - Ivacaftor + Lumacaftor

Question 39

CFTR Modulators that increase the function of the CFTR protein at the cell surface.

Answer 39

Potentiators - Ivacaftor

Question 40

CFTR Modulators approved for patients with specific gene mutations.

Answer 40

Combination Therapies - Trikafta (Ivacaftor + Lumacaftor + Tezacaftor)

Question 41

Medication that potentiates epithelial cell chloride ion transport of defective (G551D) cell-surface CFTR protein. Improving regulation of salt and water absorption and secretion in various tissues.

Answer 41

Ivacaftor

Question 42

How is Ivacaftor given?

Answer 42

2x daily (oral)

Question 43

Ivacaftor Considerations

Answer 43

MAJOR Substrate of 3A4 - not recommended with strong inducers of 3A4 - decrease dose in hepatic impairment

Question 44

How can you greatly increase the absorption of Ivacaftor?

Answer 44

Administer with High Fat Meal

Question 45

Ivacaftor Warnings

Answer 45

Hepatoxicity - stop if AST/ALT is 5x UNL Cataracts in Pediatrics

Question 46

Medication that improves the conformation stability of F508del-CFTR and increases processing and trafficking of mature proteins to the cell surface.

Answer 46

Lumacaftor

Question 47

How is Lumacaftor given?

Answer 47

2x daily (oral) - high fat food

Question 48

Lumacaftor Warnings

Answer 48

Hepatotoxicity - stop if AST/ALT is 5x ULN - or if AST/ALT is 3x ULN with ↑ Bilirubin

Question 49

Unique Adverse Drug Reactions of Lumacaftor

Answer 49

Menstrual Irregularities ↑ Blood Pressure ↑ Creatinine Kinase