Therapeutics I Exam VII (Cystic Fibrosis) Flashcards
Cystic Fibrosis
1
Q
Which ethnicity has the highest incidence of cystic fibrosis?
A
Caucasians (1 in 3,500 births)
2
Q
What is a carrier state?
A
This is when a person carries one gene for cystic fibrosis but does not actually have the disease. 1 in 25-30 caucasians carry the gene for cystic fibrosis.
3
Q
T or F: There is treatment for cystic fibrosis as well as medications that target symptoms.
A
False. There is no treatment for cystic fibrosis. The medications used only aid in symptoms.
4
Q
Why are 75% of patients diagnosed with cystic fibrosis before the age of 2 years old?
A
Every state does mandatory newborn screening which includes cystic fibrosis screeening.
5
Q
T or F: Cystic fibrosis used to be a primarily pediatric disease but now is primarily an adult disease due to advancements in medication.
A
True.
6
Q
Before medications were created for cystic fibrosis, what was the average lifespan of someone with cystic fibrosis?
A
1 year old
7
Q
As of 2025, what is the average lifespan of someone with cystic fibrosis?
A
68 years old
8
Q
In cystic fibrosis, the biggest predictor of survival is ___________.
A
FEV1
9
Q
How is FEV1 calculated for those with cystic fibrosis?
A
They do not calculate FEV1 based on % change from personal best, but percentage change from what is expected from that age population.
10
Q
Cystic fibrosis is what type of disorder?
A
It is an autosomal recessive disorder. This means both parents need to be a carrier and pass on two copies of the gene.
11
Q
Where is the mutation for cystic fibrosis located?
A
It is located in the cystic fibrosis transmembrane regulator protein (CFTR).
12
Q
What is the normal function of the cystic fibrosis transmembrane regulator protein (CFTR)?
A
In the lung, the CFTR ion channel moves chloride ions from inside the cell to outside the cell. To get out of the cell, the chloride ions move through the center of the tube formed by the CFTR protein. Once the chloride ions are outside the cell, they attract a layer of water. This water layer is important because it allows tiny hairs on the surface of the lung cells, called cilia, to sweep back and forth. This sweeping motion moves mucus up and out of the airways.
13
Q
What is the mutation seen in CFTR class I mutations for cystic fibrosis?
A
Premature stop codon
14
Q
What is the result of a premature stop codon from CFTR class I mutations?
A
This results in no functional CFTR protein being produced and no function CFTR protein on the cell surface.
15
Q
What is the most common mutation class seen in cystic fibrosis?
A
CFTR Class II Mutations
16
Q
What is the mutation seen in CFTR class II mutations for cystic fibrosis?
A
Missense and amino acid deletion resulting in a full RNA but it is misfolded and degraded before reaching the cell surface.
17
Q
What is the result of missense and amino acid deletion from CFTR class II mutations?
A
This results in no CFTR protein being trafficked to the cell surface and therefore no functional CFTR protein on the cell surface.
18
Q
What is the most common specific cystic fibrosis mutation seen in general?
A
The CFTR class II mutation F508del
19
Q
Which two classes of CFTR mutations result in no functional CFTR protein on the cell surface?
A
Class I and II mutations
20
Q
What is the mutation seen in CFTR class III mutations for cystic fibrosis?
A
Gating mutation
21
Q
What is the result of the gating mutation in CFTR class III mutations?
A
This results in a structurally normal CFTR protein at the cell surface but the channel gate itself does not open properly resulting is reduced opening time reducing the efflux of chloride.
22
Q
What is the most common specific mutation seen in CFTR class III mutations?
A
G551D
23
Q
What is the mutation seen in CFTR class IV mutations for cystic fibrosis?
A
Conductance mutations
24
Q
What is the result of the conductance mutations seen in CFTR class IV mutations?
A
This results in a full RNA produced and a structurally normal CFTR protein at the cell surface but the channel is faulty which reduces the export of chloride.
25
What is the mutation seen in CFTR class V mutations for cystic fibrosis?
Insufficient production of a sufficient quantity at the cell surface
26
What is the result of the class V mutation for cystic fibrosis?
The full RNA is produced and there is a structurally normal CFTR protein at the cell surface but there just isn't enough of them which reduces the transport of chloride.
27
T or F: Those with cystic fibrosis have a normal ratio of goblet:cilia cells unlike what is seen in asthma.
True.
28
T or F: Most cystic fibrosis mortality stems from its effects on the GI system.
False. The mortality used to stem from that but now it stems from lung issues.
29
Explain the normal physiology of a ciliated cell in the lungs.
Normal ciliated cells have CFTR proteins on the surface that pump chloride out and bring sodium in and water follows. Mucus being produced from these ciliated cells sits on top of the airway surface liquid layer which moves to expel mucus.
30
Explain the physiology of ciliated cells in the lungs for a person with cystic fibrosis.
In those with cystic fibrosis, the CFTR proteins is not there at all or dysfunctional which does not allow chloride to leave the cell which results in a net loss of sodium from the lumen into the cells and water follows sodium. This results in a thinner layer of the airway surface liquid layer.
31
The airway surface liquid layer on top of ciliated cells is also called what?
Periciliary layer
32
Within ciliated cells, those with cystic fibrosis have a complete loss of what?
Airway surface liquid layer resulting in a thick layer of mucus that is not moving out of the body.
33
Thickened and uncleared mucus in those with pulmonary fibrosis leads to an increased risk for __________.
Infections
34
What is a common infection seen in those with cystic fibrosis?
Pseudomonas Aeurginosa
35
What is the primary inflammatory cell type in cystic fibrosis?
Neutrophils
36
What are the 6 different organ systems that can be affected by cystic fibrosis?
Pulmonary, GI, sweat glands, reproductive, hematologic, and bones and joints.
37
What can happen to the female reproductive system in cystic fibrosis?
There are thickened cervical secretions which limits sperm motility making it difficult to get pregnant.
38
What can happen to the sweat glands in cystic fibrosis?
The sweat glands can't reabsorb chloride which increasing chloride concentrations within the cell which can lead to salt crystal formation.
39
What is one way that cystic fibrosis can be diagnosed later in life?
Sweat chloride testing. There will be higher concentrations of chloride in the sweat since the CFTR proteins can't export it from the gland back to the body.
40
What can happen to the bone and joints in cystic fibrosis?
Those with cystic fibrosis are at higher risk for osteoporosis and osteopenia.
41
What can happen to the red blood cells in cystic fibrosis?
There is a higher turnover of red blood cells compared tov those without cystic fibrosis.
42
What are the 14 possible clinical manifestation of cystic fibrosis?
Meconium ileus
Hyponatremic or hypochloremic dehydration
Failure to thrive
Fat-soluble vitamin deficiency
Rectal prolapse
Nasal polyposis
Chronic sinusitis/ pansinusitis
Pancreatitis
Unexplained cirrhosis
Congenital bilateral absence of the vas deferens
Recurrent pneumonia
Mucoid pesuodmonais in the lung
Bronchiectasis
Family history
43
What is meconium ileus?
This is clinical manifestation of cystic fibrosis in babies. It is went the GI track is blocked and no first poop, meconium, is released within the first 24 hours.
44
What is the result of congenital bilateral absence of the vas deferens seen in males with cystic fibrosis?
This results in infertility
45
What is bronchiectasis?
This is a clinical manifestation of cystic fibrosis. It is enlarged bronchioles due to inflammatory changes there.
46
What are the 3 ways in which cystic fibrosis can be diagnosed?
- sweat chloride testing
- genotyping
- new born screening (IRT)
47
What is the newborn screening for cystic fibrosis looking for?
Immunoreactive Trypsinogen (IRT)
48
What sweat chloride level indicates the cystic fibrosis is likely?
60 mmol/L or greater
49
What sweat chloride test level indicates that cystic fibrosis is not likely?
Less than 30 mmol/L
50
What range for sweat chloride testing indicates the cystic fibrosis is possible?
30-60 mmol/L
51
What are the 6 common complications associated with cystic fibrosis?
- Cystic fibrosis related diabetes
- Bone and joint disorders
- asthma
- GERD
- anxiety
- depression
52
When do the guidelines recommend cystic fibrosis related diabetes screenings for those with cystic fibrosis?
10 years old with an oral glucose tolerance test
53
For those with cystic fibrosis related diabetes, what is the HbA1C goal?
Les than 7
54
What is the normal first-line treatment for cystic fibrosis related diabetes?
Insulin
55
If someone with cystic fibrosis is admitted for a pulmonary exacerbations, what is sometimes monitored and for how long?
Blood glucose levels for 48 hours.
56
What is the first line treatment for anxiety and depression in those with cystic fibrosis?
SSRIs
57
When are anxiety and depression screenings recommended for those with cystic fibrosis?
12 years and older
58
What are the 5 goals of therapy for cystic fibrosis?
- normal growth and development
- reduce signs and symptoms of airway infection, inflammation, and obstruction
- slow or stop decline in pulmonary function
- return pulmonary function to pre-exacerbation status during an acute pulmonary exacerbation
- maintain quality of life
59
What are the two types of CFTR modulators?
Potentiators and Correctors
60
What is the MOA of CFTR potentiators?
They interact with mutated CFTR channels at the cell membrane and increase the opening probability of the channel. It prolongs opening time and increases the opening rate.
61
CFTR potentiators medications are applicable to which two mutation classes?
III and IV
62
What are the two CFTR potentiators we need to know?
Ivacaftor and Deutivacaftor
63
What is the MOA of CFTR correctors?
They are pharmacologic chaperones basically the correct the folding defects within the CFTR proteins and help shuttle them to the cell surface.
64
What are the 4 CFTR correctors we need to know?
Lumacaftor, Tezacaftor, Elexacaftor, and Vanzacaftor
65
CFTR correctors are only indicated for which cystic fibrosis mutation class?
Class II
66
CFTR correctors and potentiators must be used together in those with what cystic fibrosis mutation?
Class II mutations
67
What is the brand name for the CFTR potentiator, Ivacaftor?
Kayldeco
68
What 3 things were seen in the clinical trials for IVacaftor (Kayldeco)?
- increase in FEV1 of 8-12% from baseline
- 55% reduction in exacerbations
- 3kg weight gain (good in this population)
69
Ivacaftor can be used in those greater than ____________ month of age.
1 month of age
70
Most CFTR drugs have a fairly fast onset of action in terms of seeing clinical effects. What is the typical onset of action for CFTR potentiator drugs like Ivacaftor?
14 days to see FEV1 % change
71
For all CFTR drugs, what type of foods need to be consumed concurrently to administration to increase absorption of these medications?
Fatty foods
72
Most CFTR drugs are eliminated _________. What does this mean for renal dose adjustments?
Fecally
This means that no renal adjustments are needed.
73
The Ivacaftor tablets (150mg) are for those ______ years and older. Those who are younger must use the _________ ________ packets.
6 years old
Oral Granule
74
What is the frequency of dosing for Ivacaftor?
Q12H (BID)
75
How is ivacaftor dosed in those with mild-liver impairment (Child-pugh class A)?
No dosing adjustments for Ivacaftor in mild-liver impairment.
76
How is ivacaftor dosed in those with moderate-liver impairment (Child pugh Class B)?
1 tablet or 1 oral granule packet only once per day (not BID)
77
How is ivacaftor dosed in those with severe-liver impairment (Child pugh Class C)?
Use with caution in this group. Typically dosing would be 1 tablet or packet 1 time daily or even less frequently.
78
Ivacaftor is major substrate for which CYP enzyme?
CYP3A4
79
What is a drug that is a very strong CYP3A4 inducer?
Rifampin
80
__________ medication decreases the serum concentrations of ivacaftor.
Bosentan
81
Name a class of drugs that are strong CYP3A4 inhibitors.
Azole antifungals
82
If someone is on an azole antifungal like ketoconazole or clarithromycin, how is Ivacaftor dosing adjusted in response to these medications being strong CYP3A4 inhibitors?
Dosing is reduced to 2 times per week
83
If someone is on a moderate CYP3A4 inhibitor like fluconazole or erythromycin, how is Ivacaftor dosing adjusted in response?
Dosing is reduced to 1 time daily (not BID)
84
List the strong CYP3A4 inhibitors that will increase the concentrations of 3A4 substrates.
Ketoconazole, Itraconazole, Posaconazole, Voriconazole, Telithromycin, and Clarithromycin
85
List the two moderate CYP3A4 inhibitors.
Fluconazole and erythromycin
86
List the strong CYP3A4 inducers.
Rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John's Wort.
87
Concurrent use of any CYP3A4 ___________ is not recommended for patients below the age of _________ months.
Inhibitors
6 months
88
Administration of Ivacaftor is not recommended in concurrent use with what drugs?
CYP3A4 inducers like rifampin and St. John's Wort.
89
What group of drugs is contraindicated for use with Ivacaftor?
All strong CYP3A4 inducers
90
What are the 2 adverse effects seen across the board with CFTR modultors?
Liver Transaminase Elevation and Cataract Development
91
What are some other side effects associated with Ivacaftor?
Headaches, upper RT infection, nasal congestion, nausea, rash, rhinitis, dizziness, and arthralgia
92
In terms of clinical monitoring for general cystic fibrosis, what 3 things are monitored?
- lung function with FEV1 % predicted
- weight
- frequency of pulmonary exacberations
93
How often are LFTs completed for someone on ivacaftor, lumacaftor/ivacaftor?
Baseline starting
Every 3 months for the 1st year
Annually if normal
94
How often is cataract development assessed in someone on Ivacaftor?
Baseline and follow-up eye exams recommended annually for those younger than 18 years old.
95
What is the only monotherapy option available for class III and IV cystic fibrosis mutations?
Ivacaftor
96
What is the brand name for the CFTR modulator Lumacaftor/Ivacaftor?
Orkambi
97
Lumacaftor/Ivacaftor (Orkambi) can be used in patients ________ year and older who are _____________ for f508-del mutation (class II).
1 year and older
Homozygous
98
What is the typical onset of action of lumacaftor/Ivacaftor (Orkambi)?
15 days to show effect on FEV1
99
Typical Lumacaftor/Ivacaftor dosing is ______ tablets ______ daily.
2 tablets twice daily
100
What are the two formulations available for lumacaftor/ivacaftor (Orkambi)?
Tablets and oral granules
101
How is Lumacaftor/Ivacaftor dosing adjusted for those with mild-liver impairment (child pugh class A)?
No dosing adjustments are needed
102
How is Lumacaftor/Ivacaftor dosing adjusted for those with moderate-liver impairment (child pugh class B)?
2 tablets in the morning and 1 tablet in the evening or 1 packet every morning and 1 packet every other night
103
How is Lumacaftor/Ivacaftor dosing adjusted for those with severe-liver impairment (child pugh class C)?
Use with caution but it would be 1 tablet in he morning and 1 tablet at night or just 1 packet daily.
104
Lumacaftor, unlike ivacaftor, is not metabolized by ___________ but is a strong inducer of _______.
Liver
Strong inducer of CYP3A4
105
What is unique about the metabolism of Lumacaftor/Ivacaftor (Orkambi)?
Ivacaftor is a substrate for CYP3A4 while Lumacaftor is a strong inducer of CYP3A4.
106
Lumacaftor/Ivacaftor is contraindicated for use with what other drug class?
Strong CYP3A4 inducers
107
If someone is already on Orkambi, how is dosing adjusted for the initiation for azole antifungal like ketoconazole, clarithromycin, or itraconazole?
There is no dosing adjustments if the person is already on the medication.
108
How is Orkambi dosing adjusted is the patient is being initiated on it but is currently taking an strong CYP3A4 inhibitor like azole antifungals like ketoconazole, clarithromycin, or itraconazole?
Dose adjust orkambi 1 tablet daily for 1 week (or 1 pack of granules every other day) when initiating Orkambi. After one week, they can be started on the standard dose.
109
What is the weird adverse effect associated with Lumacaftor/Ivacaftor besides AST and ALT elevation and cataracts?
Dyspnea which typically goes away 3 weeks after initiation
110
What are the other adverse effects associated with lumacaftor/Ivacaftor?
Nasopharyngitis, nausea, diarrhea, upper RT infection, fatigue, abnormal respirations, increase blood CK, rash, gas, rhinorrhea, and the flu.
111
For all CFTR modulators, at what ALT, AST, and bilirubin levels should these medications be stopped?
ALT o AST 5x or greater that upper limit of normal
or
ALT or AT 3x upper limit and bilirubin is 2x or more the upper limit
112
What is the brand name for Tezacaftor/Ivacaftor?
Symdeka
113
Who is indicated for the use of Tezacaftor/Ivacaftor (Symdeka)?
6 years and older who are homozygous for F508 del mutation OR have one mutation in CFTR gene that is responsive.
114
Tezacaftor/Ivacaftor (Symdeka), is indicated for those _________ years and older and who are __________ for the F508-del mutation (class II).
6 years and older
Homozygous
115
How does dosing work for Tezacaftor/Ivacaftor?
In the morning, patients take the combination pill and in the evening they taking only ivacaftor.
116
Tezacaftor/ Ivacaftor are both substrates for _____________.
CYP3A4
117
Besides the elevated LFTs and cataracts, what are the other adverse effects associated with Tezacaftor/Ivacaftor?
Headache, nausea, sinus congestion, and dizziness
118
What is the brand name for the CFTR modulator Elexacaftor/Tezacarftor/Ivacaftor?
Trikafta
119
Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) is indicated for use in those _________ years and older who have at least one copy of the ___________ mutation.
2 years and older
F508Del mutation
120
Trikafta therapy showed a ________% increased in FEV1 from baseline.
13.8%
121
Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) is contraindicated in what population?
Severe-liver impairment (child-pugh class C)
122
All components of Trikafta (Elexacaftor/Tezacaftor/Ivacaftor) are substrates for what CYP enzyme?
CYP3A4
123
What is the black box warning associated with Elexacaftor/Tezacaftor/Ivacaftor (trikafta)?
Liver impairment
124
Besides liver impairment and cataracts, what are some other adverse effects associated with Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)?
Headache, upper RT infection, abdominal pain, diarrhea, rash, congestion, increase blood CK, rhinorrhea, rhinitis, flu, sinusitis
125
How is liver monitoring different for Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)?
Baseline
Monthly for first 6 months
Every 3 months for the next 12 months
then annually once normal
126
What is the brand name for Vanzacaftor/Tezacaftor/Deutivacaftor?
Alyftrek
127
What is unique about the dosing for Vanzacaftor/Tezacaftor/Deutivacaftor (Alyftrek)?
It is taken once day
128
Vanzacaftor/Tezacaftor/Deutivacaftor (Alyftrek) is indicated for use in those _________ years and older who have one copy of the _________ mutation.
6 years and older
F508del mutation
129
Vanzacaftor/Tezacaftor/Deutivacaftor was found to be ________________ to elexacaftor/tezacaftor/ivacaftor combination.
Non-inferior
130
Vanzacaftor/Tezacaftor/Deutivacaftor was shown to lower what value?
Sweat chloride values
131
What two populations should Vanzacaftor/Tezacaftor/Deutivacaftor not be used in?
Moderate and severe liver impairment
132
If Vanzacaftor/Tezacaftor/Deutivacaftor is being administered with strong or moderate CYP3A4 inhibitors like ketoconazole, etc., for those between 6-11 years old and less than 40kg, what is the dosing?
2 tablets once a week
133
If Vanzacaftor/Tezacaftor/Deutivacaftor is being administered with strong or moderate CYP3A4 inhibitors like ketoconazole, etc., for those between 6-11 years old and greater than 40kg, what is the dosing?
1 tablet once a week
134
Besides increased LFTs and cataracts, what are some other adverse effects associated with Vanzacaftor/Tezacaftor/Deutivacaftor?
Headache, upper RT infection, rash, and nasal congestion
135
How often are AST/ALT levels monitored for patients on Vanzacaftor/Tezacaftor/Deutivacaftor?
Baseline
Monthly for first 6 months
Every 3 months for the next 12 months
then annually once normal
136
What are the 3 types of airway clearance medications?
Bronchodilators (albuterol or salmeterol), anticholinergics (ipratropium), and mucolytics
137
What were the 3 mucolytics that was discussed?
Dornase alfa, hypertonic saline, and N-acteylcysteine
138
What is the MOA for the mucolytic, Dornase alfa?
It is recombinant human DNase 1 that cleaves DNA strands to improve mucocilliary clearance.
139
What are the 3 different types of anti-inflammatory medications?
Corticosteroids (oral or inhaled), ibuprofen, and azithromycin
140
What are the common bacterial infections seen in cystic fibrosis?
Staphylococcus aureus, Haemophlius influenzae, and pseudomonas aeruginosa
141
What are the signs and symptoms of a pulmonary exacberations in cystic fibrosis?
Increased productive cough, change in volume/color of sputum, new infiltrate on chest x-ray, deterioration in pulmonary function tests, and decreased appetite or weight loss.
142
Staphylococcus aureus is a gram _______ cocci that can be treated with what 2 antibiotics?
Gram negative cocci
Beta-lactams like amoxicillin and macrolides like erythromycin
143
Haemophilus influenzae is a gram _______ coccobacillus that is treated with what antibiotic class?
Gram negative coccobacillus
Beta-lactams like amoxicillin
144
Pseudomonas aeruginosa is a gram ________ rod that can be suppressed and treated with what two things?
Gran negative rod
Suppressed with inhaled antibiotic
Txed with two antipseudomonal antibiotics (could be beta lactams, carbepenems, or aminoglycosides, or fluoroquinolones)
145
What are the two major GI complications that occur with cystic fibrosis?
Thick GI secretions leading to fecal impaction and thick pancreatic secretions leading to pancreatic duct obstruction. They also deal with malnourishment due to lack of pancreatic enzymes.
146
How is fat malabsorption, also called steatorrhea, treated in cystic fibrosis?
Pancreatic enzymes like Crean or Pancreaze that are taken with meals as well as supplemental fat-soluble vitamins.
147
How are intestinal obstructions treated in cystic fibrosis?
Often patients are given Miralax or Golytely. If those fail, then N-acetylcysteine is given for 24 hours.
