Cystic Fibrosis

What is cyproheptadine?

appetite stimulant

If a CF patient has a pseudomonas infection, what is the recommended treatment?

-2 antibiotics from different classes 1. zosyn 2. cefepime 3. ciprofloxacin 4. meropenem 5. tobramycin/amikacin

What is kalydeco (Ivacaftor)?

-acts on non-functional, properly localized CFTR (potentiator) -works on class III mutation *patient must have at least one copy of G551D -keeps chloride ion channel open to allow them to move in and out *showed 12% increase in FEV1 -150mg BID with fat containing food -costs over $300,000 a year

What are the hematologic complications of CF?

-anemia -chronic hypoxemia -abnormal bleeding

Why do CF patients take azithromycin for chronic therapy?

-azithromycin has anti-inflammatory effects -alters biofilm formation -improves overall lung function *dosing is three times a week

What is the pathophysiological effect for mutations in the CTFR gene?

-defect in the chloride ion channel which decreases the amount of chloride and increases the amount of sodium which causes an increase in the viscosity of fluid excreted due to disrupted H20 movement across the cell membrane -increased viscosity and mucosal secretions leads to obstruction of the exocrine glands and dehydration of the airway surfaces

What are the reproductive complications of CF?

-delayed puberty -infertility

What is DIOS?

-distal intestinal obstruction syndrome -obstruction of the right colon and/or terminal ileum with viscid fecal matter -treat with hydration, Miralax, enemas, surgical resection, N-acetylcysteine

What complications occur in the hepatobiliary system due to cystic fibrosis?

-due to bile duct obstruction from abnormal bile composition and flow -hepatomegaly, splenomegaly, and cholecystitis may occur -elevated AST, ALT, AP, and bilirubin -portal hypertension

What are the skin/salivation complications of CF?

-high concentration of sodium and chloride in the sweat -excessive sweating -impaired saliva production -increased viscosity of saliva

What is the benefit of using ibuprofen in CF patients?

-high dose ibuprofen inhibits the migration, adherence, swelling, and aggregation of neutrophils, as well as the release of lysosomal enzymes -decreases decline of FEV1 -decreases hospitalizations *20-30 mg/kg BID

How does hypertonic saline work as a mucolytic agent?

-increases hydration of airway surface liquid via osmotic flow -breaks ionic bonds in mucus -stimulates cilial beat via release of PG E2 -causes sputum production and cough to improve airway obstruction *must use bronchodilator before using

What are the causes of CF-related diabetes?

-insulin/glucagon deficiency -undernutrition -malabsorption -liver dysfunction -elevated energy expenditure -abnormal absorption intestinal transit time

What is dornase alfa (Pulmozyme)?

-mucolytic agent -recombinant DNA enzyme -selectively cleaves extracellular DNA from pulmonary secretions -improves viscoelastic properties of secretions *promotes airway clearance of mucus **must use bronchodilator before using this agent

What are the GI complications associated with cystic fibrosis?

-newborns may present with meconium ileum -infants and small children have increased frequency of stools and steatorrhea -older patients have obstruction of pancreatic ducts and intestinal tract, constipation, abdominal cramping, and flatulence *decreased enzyme production by the pancreas leads to malnutrition and causes the patient to fail to thrive -GERD, dysmotility, intussusception, volvulus, atresia, rectal prolapse, jaundice, and GI bleed

What are the musculoskeletal complications of CF?

-osteoporosis -poor nutrition -decreased body mass -clubbing of fingers and toes

What is Orkambi (lumacaftor/ivacaftor)?

-potentiates CFTR function, treats type II mutation Lumacaftor- improves the conformational stability of delta-F508, resulting in increased processing and trafficking of mature CFTR protein to the cell surface *2 tablets (200mg/125mg) PO q12H with fat containing meals *only showed 4% increase in FEV1

What is Ursodiol?

-treatment for hepatobiliary disease -slows disease progression by decreasing bile flow -displaces toxic bile acids and reduces liver enzymes -stimulates bicarbonate and chloride secretion

Why do we not recommend chronic use of prednisone in CF patients?

-while patients in the short term improved, over long term use the side effects of systemic corticosteroids outweighed the benefits

If a CF patient has H. influenzae infection, what is the recommended treatment?

1. 3rd generation cephs 2. zosyn 3. cefepime 4. meropenem 5. ciprofloxacin 6. tobramycin

What are the pharmacokinetic challenges in cystic fibrosis?

1. absorption -differences in gastric pH -slower GI motility 2. distribution -larger volume of distribution 3. metabolism -possible difference in hepatic clearance 4. elimination -increased renal clearance

What are some of the pulmonary complications of cystic fibrosis?

1. air trapping 2. mucus plugging 3. cystic lesions 4. hypoxemia 5. atelectasis 6. Pulmonary HTN 7. respiratory failure 8. bronchitis *pulmonary function declines at 2% yearly

What are some of the Non-Rx treatments for CF?

1. airway clearance therapy -break up mucus -high frequency chest wall oscillation 2. nutritional supplementation -maintain BMI helps lung function -caloric intake 110-200% of healthy population

What are the bronchodilators for cystic fibrosis?

1. albuterol (nebulized or HFA inhaler) 2. levalbuterol -preferred if patient has medical heart defect -its more selective

KT will need to take the following inhaled medications. In what order should she take them? A. Tobramycin inhaled B. dornase alfa C. albuterol

1. albuterol - opens up the airway 2. dornase alfa - clears the mucus 3. tobramycin inhaled - gets better penetration of the lung after airway is cleared

If a CF patient has an infection caused by burkholderia, what is the recommended therapy?

1. bactrim 2. meropenem

If a CF patient has an infection caused by nocardia, what is the recommended therapy?

1. bactrim 2. minocycline 3. linezolid

If a CF patient has an infection caused by stenotrophomonas, what is the recommended therapy?

1. bactrim 2. zosyn 3. levofloxacin or moxifloxacin 4. timentin plus aztreonam

Which corticosteroids do we use for CF patients and when?

1. budesonide (Pulmicort) 2. fluticasone (Flovent) -only use inhaled corticosteroids in patients with CF and asthma

What are clinical signs and symptoms of cystic fibrosis?

1. chronic sinus infections 2. polyps in the sinus cavity 3. shortness of breath 4. cough with sputum production 5. digital clubbing (in older patients)

What are the antibiotic therapy goals for CF patients?

1. early lung disease -primary goal is to detect infection early and eradicate and prevent colonization 2. chronic maintenance antibiotics -primary goal is to suppress bacterial growth 3. acute exacerbations -intensive antibiotics given to drastically reduce bacterial load and return lung function to pre-exacerbation level or better

What are diagnostic finding of cystic fibrosis?

1. flat diaphragm and increased chest diameter on an X-ray 2. decreased FEV1 3. increased WBC count

What are the pharmacological treatment options for cystic fibrosis?

1. gene therapy- to correct CFTR mutation 2. CFTR modulators- correct defect in ion transport 3. hypertonic saline- help with thick secretions and ASL depletion 4. airway clearance, bronchodilators, dornase alfa -help with mucociliary clearance 5. antimicrobials/steroids -treat infections and inflammation

What are the pharmacokinetic considerations for putting CF patients on antibiotics?

1. larger volume of distribution in CF patients 2. increased clearance 3. shorter half life of drugs 4. low sputum concentrations 5. decreased action of antibiotics

If a CF patient has staph. aureus infection, what is the recommended treatment?

1. nafcillin or cefazolin (MSSA only) 2. vancomycin 3. linezolid 4. clindamycin

What is the diagnostic criteria for CF?

1. one or more clinical features of CF PLUS 2a. two CF mutations OR 2b. two positive sweat tests OR 2c. abnormal nasal potential difference

What are considerations before starting a CF patient on azithromycin?

1. patients with colonization of atypical mycobacteria -eliminates treatment option -could promote development of resistant strain 2. patient weight 3. not colonized with pseudomonas -eliminates treatment option if don't have pseudomonas already

What are signs and symptoms of CF-related diabetes?

1. polydipsia or polyuria 2. failure to gain or maintain weight 3. failure to grow 4. delayed progression of puberty 5. chronic decline in pulmonary function

What are common pathogens responsible for infection in late stages of cystic fibrosis?

1. pseudomonas 2. stenotrophomonas maltophilia 3. alcaligenes xylosoxidans 4. burkholderia cepacia 5. fungi and non tuberculin mycobacteria

What are the traditional presenting symptoms of CF?

1. recurrent pneumonia 2. chronic sinusitis 3. nasal polyps 4. failure to thrive 5. meconium ileus 6. dehydration 7. hepatitis 8. infertility

What are common pathogens responsible for infection in early stages of cystic fibrosis?

1. staph. aureus 2. H. influenzae 3. pseudomonas

What antibiotics are recommend for prophylaxis for CF patients?

1. tobramycin 2. aztreonam 3. colistimethate *all are inhaled **given on 28 days on/ 28 days off interval to prevent resistance

How many classes of mutations for CF do we have?

5 Class I- most severe -no CFTR synthesis Class II- most common (have drug for this) -CFTR trafficking defect delta-F508 Class III (have drug for this) -dysregulation of CFTR -G551D present Class IV -defective chloride conductance Class V -reduced CTFR transcription and synthesis

Which of the following medications is not commonly suggested as routine chronic maintenance drug therapy in CF? A. Azithromycin B. Dornase alfa C. ibuprofen D. Prednisone

D. prednisone

In which chromosome does the mutation that causes cystic fibrosis occur?

chromosome 7- CTFR gene *autosomal recessive

What is the most common mutation responsible for cystic fibrosis?

delta F508

How are pancreatic enzyme replacement medications dosed for CF patients?

dosed based on the lipase component *only use brand name, generic is not well regulated and many patients have treatment failure

How do you treat CF-related diabetes?

mostly just insulin, oral agents not as effective