Resp - Cystic fibrosis treatment Flashcards
What is CF?
genetic disorder affecting the lungs, pancreas, liver, intestine, and reproductive organs
What are the signs of CF?
pulmonary disease, with recurrent infections and the production of copious viscous sputum, and malabsorption due to pancreatic insufficiency
Complications include hepatobiliary disease, osteoporosis, cystic fibrosis-related diabetes, and distal intestinal obstruction syndrome
Aims of treatment
Preventing and managing lung infections
Loosening and removing thick, sticky mucus from the lungs
Preventing or treating intestinal obstruction
Providing sufficient nutrition and hydration
What function is a key predictor?
lung function - optimising lung function is a major aim of care
What are the Non-Drug Treatment?
Provide advice on airway clearance, nebuliser use, musculoskeletal disorders, physical activity, and urinary incontinence (by specialist physiotherapists).
Regular exercise improves both lung function and overall fitness
What are the Drug Treatment?
Treatment is based on the prevention of lung infection and the maintenance of lung function.
Patients, who have clinical evidence of lung disease, the frequency of routine review should be based on their clinical condition.
Adults should be reviewed at least every 3 months.
More frequent review is required immediately after diagnosis
Mucolytics
Patients with cystic fibrosis who have evidence of lung disease should be offered a mucolytic.
Dornase alfais the first choice mucolytic.
If there is an inadequate response,dornase alfaand hypertonicsodium chloride, or hypertonicsodium chloridealone should be considered.
Mannitoldry powder for inhalation is recommended as an option whendornase alfais unsuitable, when lung function is rapidly declining, and if other osmotic drugs are not considered appropriate
Staphylococcus aureus
Offer an antibacterial oral or IV
Pseudomonas aeruginosa
Offer an oral antibacterial in combination with an inhaled antibacterial
Aspergillus fumigatuscomplex
Offer an antifungal drug only to suppresschroniccomplex respiratory infection in patients with declining pulmonary status
Inheritable autosomal _________ disease
reccesive
Mutations of the cystic fibrosis transmembrane conductance regulator ______ gene
CFTR
Which systems are affected?
Pulmonary and GI systems
Epidemiology of CF
equally diagnosed in males and females
What is the most common mutation
ΔF508 - a three base-pair deletion that should code for a phenylalanine (position 508)
What are the main causes
- CFTR gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long.
- CFTR gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long.
-
Cellular processing of CFTR:
- Synthesis of mRNA (transcription)
- translation and folding in the ER (splicing and folding)
- Glycosylation and vesicle packaging in the Golgi
- Insertion into and retrieval from membrane (stabilioty)
- Activation by ATP binding and cAMP-dependent phosphorylation (activity and conductance)
CFTR In Cystic Fibrosis
CFTR Channel: Chloride ions aren’t transported through chloride channels in CF
Chloride ions – reduced extraceullulary (on surface of epithelium)
Affects constituency of mucus
Na+ and Cl− on airway surfaces
coupled to reduced water flow to the airway lumen
dehydrating mucus
Reduced HCO3− to the airway surface, acidifying layer
Diagnosis of CF
Large number of CFTR mutations limits utility of DNA tests in diagnosis but can be done
The heel prick test blood test newborns – common variants
Sweat test for chlorine levels (>60mM for adults)
How to manage CF?
- Life-style and pyschological support required
- Maintenance to improve QoL and limit exacerbations
Treatment objectives:
Promote clearance of secretions
Control lung infection
Provide adequate nutrition
Prevent intestinal obstruction
What is the process of CF lung disease?
- mutations of CFTR gene
- ion transport abnormalities
- overly viscous mucous
- impaired mucous clearance (mucolytics)
- infection (antibiotics)»_space; inflammation which leads to tissue damage
What happens in a pulmonary mucous clearance??
airway surface liquid protects lung and pericilary layer and mucus layer
the PCL is a grafted brush of tethered mucins
and mucus is a visocoelastic fluid
What do ASL layers do?
trap and clear inhlaed pathogens from lung via mucociliary transport
mucus consistency affects this
ciliary clearence becomes ineffective
Inhaled dornase alfa
DNA forms polymers thickening mucous
Dornase alfa is a DNAse
Reduces viscosity of mucous
Inhaled hypertonic saline
Disrupts ionic bonds supporting entanglements
Disassociates DNA from mucous proteins
Improved access to endogenous proteolytics
Inhaled mannitol
Hydrates mucous
Osmotic mechanism
name examples of bronchodialators
Commonly used for acute relief of obstruction
No clinical studies on exacerbation
Chest physiotherapy
Used to aid clearance of mucous from the lungs
Oral corticosteroids
Reduce rate of decline in lung function
Reduce frequency of infections
Unwanted effects preclude long term use
Inhaled corticosteroids
Don’t improve lung function unless airway hyperreactivity
Pancreatic enzyme supplements
Supplements contain protease, lipase and amylase
Inactivated by stomach acid (with food, enteric coating)
Why do you need a high calorie diet?
for digestion
