Cystic Fibrosis Flashcards
1
Q
Cystic Fibrosis
A
- Progressive, life-limiting, genetic disorder
- Autosomal recessive
- More than half of CF population >= 18 y.o.
2
Q
Pathophysiology
A
- Mutation of CFTR gene causing CFTR protein to dysfunction
- Regulates chloride transport across cell membrane
- Without cholride, mucus becomes thick and sticky
3
Q
CF Mutations
A
- Different mutations result in different levels of CFTR function
- > 2000 mutations
- F508del - most common mutation
- Protein misfolded and doesn’t reach cell surface
4
Q
CF Diagnosis
A
- Newborn screening: measures immunoreactive trypsinogen, chemical made by pancreas
- Gold standard: sweat test, sample of sweat collected from skin (Positive >=60 mmol/L of chloride)
- Chromosomal analysis
5
Q
CF Involved Organ Systems
A
- GI
- Hepatic
- Pulmonary
- Reproductive
- Bone
6
Q
Signs/Symptoms
A
- Poor growth/weight gain
- Meconium ileus
- Frequent greasy, bulky stools OR difficulty in bowel
- Frequent lung infections
- Wheezing/SoB
- Persistent coughing, occasional sputum
- Chronic sinusitis
- Very salty skin
- Male infertility
- Nasal polyps
7
Q
GI Goals
A
- Control pancreatic insufficiency by providing adequate enzyme supplementation
- Optimize growth and nutritional status
- Promote healthy bowel habits
- Maintain normal vitamin levels
8
Q
GI Tract Manifestations
A
- Insufficient secretion of pancreatic enzymes
- Fat-soluble vitamin malabsorption
- Insulin deficiency
- Intestinal obstruction: meconium ileus, DIOS
9
Q
Pancreatic Insufficiency
A
- Maldigestion of nutrients
- Symptoms: steatorrhea, frequent loose stools, flatulence, cramping, bloating, poor weight gain constipation
- Below age-related norms of weight AND height
- Result of pancreatic enzyme deficiency
10
Q
PERT
A
- Pancreatic Enzyme Replacement Therapy
- Creon, Zenpep, Pancreaze, Ultresa, etc
- Contain lipase, protease, amylase
- Enzyme brands aren’t interchangeable
- DR capsules with enteric-coated microspheres or minitablets
- Porcine derived
11
Q
PERT Dosing
A
- Based on TBW or fat ingested
- Dosed on lipase units
- Taken with every meal and snack
Dosing Options
- 500-2500 units/kg/meal
- 10,000 units/kg/day
- 4,000 units/g of dietary fat/day
12
Q
PERT Capsules
A
- Do not crush or chew contents of DR capsules
- Can open capsule and add to room temperature, acidic foods (applesauce)
- Must eat immediately and follow with water, juice, formula, breast milk
- Regular release tablets are swallowed whole with sufficient liquid
13
Q
PERT AE
A
- Mucosal irritations
- Fibrosing colonopathy and colonic strictures (high doses > 6000 lipase units/kg/meal): diarrhea, constipation, abdominal pain
14
Q
PERT Monitoring
A
- Stool fat content
- Abdominal symptoms
- Nutritional intake
- Growth
15
Q
Fat Soluble Vitamins
A
- Replace A, D, E, and K
- Doses higher compared to those without CF
16
Q
Nutritional Intake
A
- Energy intakes can be greater than standard for general population
- BMI >50-85% for age
- May require nutritional supplementations like EN
- Promotes healthy pulmonary function
17
Q
Insulin Deficiency
A
- CF related diabetes
- Prevalence increases with age
- Associated with worse lung fxn, poorer nutritional status, increased pulm. infections
- Shares features of DM I and II
- Treat with insulin
18
Q
DIOS
A
- Distal intestinal obstruction syndrome
- Symptoms: cramping abdominal pain, poor appetite, abdominal distension
- Therapy: electrolytes lavage solutions: passage of stool being symptom resolution
19
Q
Hepatic System + CF
A
- Bile duct obstruction can lead to cirrhosis, portal hypertension
- Ursodiol: controversial
- Dosing: 15-20 mg/kg/day; divided BID
20
Q
Pulmonary Systems
A
- Manifestations result from impaired mucociliary clearance resulting in accumulation of viscous mucus in airways
- Consequences: obstruction, inflammation, infection
- Chronic rhinitis, sinusitis, nasal polyps
21
Q
Pulmonary System Goals
A
- Decrease long-term rate of lung fxn decline
- Airway clearance techniques (ACT)
- Anti-inflammatory agents
- Mucus alteration
- Restore airway surface liquid
- Bronchodilators
- Chronic antibiotics
22
Q
ACT
A
- Improve ventilation, reduce accumulation of secretions
- Done at least BID
- Include chest/back percussions, exercise, percussion vest
- Bronchodilator pre-treatment
23
Q
Ibuprofen Use
A
- Anti-inflammatory Treatment
- Decreased rate of decline of FEV1
- Given to 6-17 y.o. with mild lung disease (FEV >= 60%)
- [Peak plasma] = 50-100 mg/L
- 20-30 mg/kg/dose given BID
24
Q
Azithromycin Use
A
- Anti-inflammatory treatment
- Unclear if anti-inflammatory effects are due to antimicrobial and/or immunomodulatory mechanisms
- Slow decline in FEV1 in CF patients with Pseudomonas
- Decreased pulmonary exacerbation
- Dosing: 3x/week
25
Mucus Alteration Options
- Pulmozyme
- Nebulized hypertonic saline
- Mannitol inhalation powder
26
Pulmozyme
- Aerosolized recombinant dornase alfa (DNase)
- Decreases viscosity of sputum
- Clinical trial show modest improvements in DEV and pulmonary exacerbation
- Dose: 2.5 mg nebulized once daily or BID
- AE: hoarseness, voice alteration, and pharyngitis
- Use selected nebulizer, compressor
- Don't mix with other medications in nebulizer
27
Nebulized Hypertonic Saline
- Draws water into airways, improve mucus clearance
- 3-7% nebulized daily to BID
- Improve lung fxn, decrease exacerbations requiring antibiotics
- May cause bronchospasm, pre-treat with bronchodilator
- Hyper-Sal, PulmoSal, Nebusal (PulmoSal buffered with Na-bicarb)
28
Mannitol Inhalation Powder
- Bronchitol
- Osmotic agent, draws water into the airways, thins mucus
- 18 years of age and older
- Dry powder inhaler
- Bronchitol tolerance test
- Albuterol prior to use
- Inhale contents of 10 capsules twice daily
- AE= bronchospasm, hemoptysis
29
Pulmonary Chronic Therapy
- Inhaled corticosteroids: if patient also has asthma, not used routinely
- Inhaled SABAs: pre-treat for irritating inhaled therapies
30
Pulmonary Infection Pathogens
- S. aureus: major pathogen first year of life
- H. influenzae: major pathogen by 3 y.o.
- P. aeruginosa: Major pathogen by age 5, colonized
- Burkholderia, Stenotrophomonas, Aspergillus, MRSA
31
Chronic Antibiotic Therapy
- Intention is to prolong time between acute exacerbations
| - Usually inhaled: TOBI/Tobi podhaler, Cayston
32
TOBI
- Tobi Podhaler
- Nebulized and dry powder inhaler formulations of tobramycin
- P. aeruginosa colonization
- Given BID: 28 days on treatment, 28 days off
33
Tobi Podhaler Administration
- 4 capsules inhaled BID
- Inhale 2 times from each capsule
- Take doses 12 hours apart
- Store capsules in blister card until ready to use
- Do not swallow capsules
34
Cayston
- Nebulized aztreonam
- P. aeruginosa colonization
- Give TID; 28 days on treatment, 28 days off
- Altera nebulizer system
35
Sequence of Inhaled Medications
1. Bronchodilator
2. Hypertonic Saline
3. Pulmozyme
4. Airway clearance techniques
5. Aerosolized antibiotics
36
CF + Additional Systems
- Reproductive system: majority of males have congenital bilateral absence of the vas deferens
- Bone disease: low bone density, secondary to vitamin D deficiency, systemic inflammation, corticosteroid use
37
Kalydeco
- Ivacaftor, CFTR modulator
- Targets the defective CFTR protein, >= 4 month
- Patient with specific mutations, not homozygous F508del
- Improves: lung function, weight gain, QoL
- Expensive
38
Kalydeco Dosing
- Reduce dose: moderate-severe hepatic impairment
- CYP3A inhibitors: ketoconazole, fluconazole, adjust dose
- Avoid: the strong inducers (CBZ, phenobarbital, phenytoin)
- Avoid grapefruit
- Give with fat containing food
- Mix granules in 5 mL of soft food or liquid at or below room temperature (stable for 1 hour)
39
CFTR Modulator Warnings
- May increase hepatic transaminases: monitor liver fxn, baseline every 3 mo during 1st year of therapy and yearly after
- Cataracts
- CNS effects: dizziness, may impair abilities
40
Orkambi
-CFTR modulator
-Lumacaftor + ivacaftor
-2 copies of F508del, >= 2 years
Drug Interactions
-Lumacaftor: strong inducer CYP3A, avoid benzos and immunosuppressants
-Hormonal contraceptives have decreased effectiveness
-Respiratory AEs during initiation: chest discomfort, dyspnea
41
Symdeko
- CFTR modulator
- Tezacaftor (100mg) + ivacaftor (150 mg) tablet and ivacaftor (150 mg) tablet
- Co-packaged: take combo tablet in morning and monotherapy in evening
- >= 6 y.o. with 2 copies of F508del or at least one mutation that is responsive
42
Trifakta
- CFTR modulator
- Elexacaftor + tezacaftor + ivacaftor
- >= 12 y.o. with at least one copy of F508del
- Supplied as 2 separate products packaged together: Combination and ivacaftor
43
Acute Pulmonary Exacerbation
- New/increased cough, sputum production, dyspnea with exertion
- Increased nasal congestion or drainage
- Change in sputum appearance
- Decreased exercise tolerance, energy, pulm fxn tests, appetite, weight
- +/- Fever
- Chest x-ray not routinely done, may not shown changes over baseline
44
Acute Pulmonary Exacerbation
- Diagnosis: changes from patient's baseline
| - Goals: decrease pulmonary signs/symptoms, eradication of P. aeruginosa is unlikely
45
Acute Pulmonary Exacerbation Treatment
- Antibiotics oral or IV
- Choice depends on cultures/sensitivity reports, dose at upper end (approach normal pop parameters with age)
- P. aeruginosa generally uses aminoglycosides in combo with antipseudomonal penicillin
- Increased nutrition
- Increased ACT
46
Investigational Therapies
- New CFTR modulators
- Antibiotics: inhaled levofloxacin
- Non-porcine derived enzymes
