Lecture 5 - Management of Cystic Fibrosis.pptx

CRICOS: 00233E | TEQSA: PRV12076 4016PHM Integrated Pharmacotherapeutics V Management of Cystic Fibrosis Queensland Australia ACKNOWLEDGEMENT OF COUNTRY Griffith University acknowledges the people who are the Traditional Custodians of the land. We pay respec...

CRICOS: 00233E | TEQSA: PRV12076 4016PHM Integrated Pharmacotherapeutics V Management of Cystic Fibrosis Queensland Australia ACKNOWLEDGEMENT OF COUNTRY Griffith University acknowledges the people who are the Traditional Custodians of the land. We pay respect to the Elders, past and present, and extend that respect to all Aboriginal and Torres Strait Islander peoples. CRICOS: 00233E | TEQSA: PRV12076 Together, Together, Together,Sid Together, Sid SidDomic Sid Domic Domic Domic What is Cystic Fibrosis? Inherited autosomal recessive condition Most common cause of bronchiectasis and chronic suppurative lung disease in children Mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) Defects can cause changes in CFTR production, location or function CRICOS: 00233E | TEQSA: PRV12076 Manifestations of Cystic Fibrosis Multisystem condition Affects: Lungs Gastrointestinal tract Pancreas Liver Sinuses Sweat glands Kidneys Bones Reproductive system CRICOS: 00233E | TEQSA: PRV12076 Prognosis Life-long condition, no cure Affects 1 in 2500 in Australia Increasing lifespan Most patients live into adulthood Average predicted survival – 44 years Progressive lung disease major cause of morbidity and mortality CRICOS: 00233E | TEQSA: PRV12076 Management Principles of CF Effective airway clearance – physical and drug Anti-inflammatory treatment Drug treatment to correct CFTR function (some patients) Early aggressive antibiotic therapy Strict infection control measures Managing non-respiratory aspects CRICOS: 00233E | TEQSA: PRV12076 Typical Treatment Intensive daily physiotherapy to clear the lungs Enzyme replacement capsules with food to aid digestion Antibiotic therapy to treat lung infections Aerosol mist inhalations to open airways Salt and vitamin supplements High calorie, high salt, high fat diet Exercise CRICOS: 00233E | TEQSA: PRV12076 Airway Clearance Aim: Remove secretions from the bronchi – reduce airway obstruction and risk of infection Combination of physical methods and drug treatments Mucolytic ± pre-treatment with a bronchodilator CRICOS: 00233E | TEQSA: PRV12076 Aerosolised Mucolytics – Dornase Alfa Dornase alfa (recombinant human DNase) Cleaves extracellular DNA and reduces sputum viscosity 2.5 g by inhalation via nebulizer, once daily for 3 months (trial) Treatment can continue if no decrease in FEV1 during trial and clinical benefit demonstrated CRICOS: 00233E | TEQSA: PRV12076 Aerosolised Mucolytics – Nebulised Hypertonic Saline Nebulised hypertonic saline Improves lung function and reduces acute infective exacerbations Sodium chloride 6% solution if tolerated otherwise 3% solution used Hypertonic saline challenge should be performed prior to it being prescribed Can cause bronchospasm in susceptible individuals CRICOS: 00233E | TEQSA: PRV12076 Anti-inflammatory Treatment Aim: Reduce host inflammatory response and decrease lung injury Azithromycin, oral, 250 mg three times a week Improves lung function, reduces the rate of exacerbations, achieve weight gain Best evidence for use in patients with Pseudomonas aeruginosa infection Do not routinely prescribe oral or inhaled corticosteroids CRICOS: 00233E | TEQSA: PRV12076 Aerosolised Mucolytics – Inhaled Dry Powder Mannitol Inhaled dry powder mannitol Improves mucociliary clearance and lung function 400 mg (10 x 40 mg capsules) inhaled via dry powder inhaler, twice daily Used in children 6 years or older Mannitol Tolerance Test should be undertaken prior to use due to risk of bronchospasm More irritant than other aerosolised mucolytics CRICOS: 00233E | TEQSA: PRV12076 CFTR Modulator Therapy Aim: Improve CFTR function Ivacaftor Lumacaftor + Ivacaftor Tezacaftor + Ivacaftor Elexacaftor + Tezacaftor + Ivacaftor Mutation-specific drugs Drug interactions common CRICOS: 00233E | TEQSA: PRV12076 Exacerbations of CF Respiratory infection should be treated promptly at onset of signs or symptoms Common respiratory symptoms: Cough, increased sputum Other respiratory symptoms: Tachyponea, increased work of breathing, crackles, wheeze Non-respiratory symptoms: Loss of appetite, weight and energy CRICOS: 00233E | TEQSA: PRV12076 Airway Infection and Antibiotics Lungs become infected in early infancy Chronic colonisation, biofilm formation Aim: To eradicate infection before biofilm formation Contributes to lung damage through neutrophil migration and subsequent release of elastase; neutrophil DNA released contributing to sputum viscosity Common organisms: Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa and Aspergillus spp CRICOS: 00233E | TEQSA: PRV12076 General Principles of Antibiotic Therapy in CF Aim: Early eradication or to suppress chronic established infections and manage exacerbations Guided by local guidelines Different doses, dosing intervals, durations differ in CF patients Choice of drug guided by CF management plan and infecting organism and its susceptibility Respiratory cultures obtained 4 times a year CRICOS: 00233E | TEQSA: PRV12076 Management of Infections caused by Pseudomonas aeruginosa Pseudomonas aeruginosa becomes the dominant organism in teenage/adult years Local protocols followed e.g. CHQ Empirical Antimicrobial Therapy for Children with Cystic Fibrosis Eradication vs exacerbation CRICOS: 00233E | TEQSA: PRV12076 Nutrition Good nutrition is associated with better growth and respiratory outcomes Pancreatic exocrine insufficiency To maintain nutritional status Specialist dietary advice 110-200% of the daily energy requirements of the general population Supplementation with fat soluble vitamins (A, D, E and K) and salt CRICOS: 00233E | TEQSA: PRV12076 Management of Pancreatic Exocrine Insufficiency Aim: To allow for adequate digestion and absorption of fat, protein and starch. Oral pancreatic enzyme supplements Adult starting dose 40,000 units of lipase with each main meal and half dose (20,000 units) for snacks Dose should be increased in response to symptoms and maintained at the lowest effective dose Proton pump inhibitor therapy CRICOS: 00233E | TEQSA: PRV12076 Gastrointestinal Health General bowel problems common e.g. abdominal bloating, constipation, diarrhoea Mild increases in liver enzymes (especially alkaline phosphatase) Cholelithiasis can occur - ursodeoxycholic acid to rebalance bile salts CRICOS: 00233E | TEQSA: PRV12076 Cystic Fibrosis-Related Diabetes Occurrence increases with age Affects ~10% of adolescents and ~40% of adults Aim: Good control of CFRD to maintain kidney health First-line therapy – insulin High-calorie diet is recommended rather than typical dietary restrictions recommended for Type 1 and Type 2 diabetes CRICOS: 00233E | TEQSA: PRV12076 Bone Health Increased risk of osteoporosis and osteopenia Aim: Decrease the onset of osteopenia and osteoporosis Management includes: standard treatments including nutrition, exercise, vitamin D, calcium supplements, bisphosphonates Additional management: limiting progression of chronic suppurative lung disease vitamin K supplementation recognising and treating delayed puberty. CRICOS: 00233E | TEQSA: PRV12076 Kidney Disease Incidence increases with age Estimated creatinine clearance rate is not sensitive in CF Causes: Antibiotics e.g. aminoglycosides, vancomycin CFRD Renal calculi Calcineurin drugs (after transplant) Strategies to maintain renal function Use of inhaled vs oral antibiotics TDM CRICOS: 00233E | TEQSA: PRV12076 Hearing Repeated doses of antibiotics - aminoglycosides CRICOS: 00233E | TEQSA: PRV12076