cystic fibrosis

background

CF is an incurable disease caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR)

this mutation causes abnormal transport of chloride, bicarb, and sodium ions, leading to think, viscous secretions

the thick mucus affects the lungs, pancreas, liver, and intestines --> difficulty breathing, lung infections, and digestive complications

most diagnosed by 2yo

diagnosis

sweat test --> measures amount of chloride in sweat (will be high)

signs and symptoms

salty tasting skin

poor growth

poor weight gain

mucus production

frequent lung infections

coughing and SOB

steatorrhea (fatty stools)

malnutrition

inhaled meds for CF

1st --> inhaled bronchodilators --> opens the airway

2nd --> hypertonic saline --> mobilized mucus to improve airway clearance

3rd --> dornase alfa --> decreases viscosity of mucus to promote clearance

4th --> chest physiotherapy --> mobilizes mucus to improve airway clearance

5th --> inhaled antibiotics --> controls airway infection

minimizing lung complications

administering inhaled meds in the correct order is critical

airway clearance meds are given before inhaled antibiotics

the drug is delivered directly to the lungs, resulting in minimal systemic absorption

intermittent infection

most common organisms seen early in the disease --> s. aureus and h. flu

pseudo is also common in adolescents and adults

acute pulmonary exacerbations are shown by a decrease in FEV1

for infections caused by psuedo, two IV drugs are recommended to provide potential synergy (w/ aminoglycosides) and prevent resistance

doses tend to be larger than normal

chronic infection

inhaled antibiotics are recommended for patients with chronic pseudomonas

treatment is cycled with 28 days on, followed by 28 days off

if a patient is using a bronchodilator and/or mucolytic, these should be given prior to the antibiotic

azithromycin has NO direct activity against psuedo, but can improve lung funciton and decrease exacerbations

inhaled airway clearance therapies

bronchodilator

hypertonic saline --> delivered via nebulizer

dornase alfa (pulmozyme)

dornase alfa

decreases viscosity of mucus

store ampules in the refrigerator

protect from light

do not mix with any other drug in the nebulizer

inhaled antibiotics

** target psuedo

tobramycin (solution --> TOBI, kitabis) (capsule --> TOBI podhaler)

aztreonam (cayston) --> solution for inhalation

azactam (IV)

tobramycin

SEs --> ototoxicity, tinnitus, voice alteration, mouth and throat pain

give for 28 days, followed by 28 days off

doses must be at least 6 hours apart

solutions --> store in fridge (can be stored at room temp for up to 28 days); do not mix with any other drug in the nebulizer

capsule --> store at room temperature, use with podhaler, do not swallow

aztreonam

SEs --> allergic reactions, bronchospasm, fever, wheezing, cough, chest discomfort

give for 28 days, followed by 28 days off

doses must be at least 4 hours apart

refrigeration recommended (can be kept at room temp for 28 days)

do not mix with any other drug in the nebulizer

oral antibiotic

decreases inflammation and exacerbations

azithromycin (zithromax)

pancreatic enzyme products

help break down fat, starches, and protein

pancrelipase is a natural product harvested from porcine pancreatic glands which contains a combo of lipase, amylase, and protease

PEPs are formulated to dissolve in the more basic pH of the duodenum

the dose is individualized for each patient based on the lipase component

dose is adjusted until stools are normalized

pancrelipase

creon, viokace, zenpep

max dose for all ages 10,000U/kg/day

warnings --> colonic strictures, mucosal irritation

SEs --> abdominal pain, flatulence, nausea

common issues with PEPs

PEP formulations are not interchangeable

viokace is the only PEP that is a tablet --> it in non-enteric coated and must be given with a PPI

all other PEPs are capsules --> do not crush or chew, DR can be sprinkled on acidic foods (pH <4.5), do not retain capsule contents in the mouth

take PEPs before or with all meals and snacks. high fat meals may require higher doses (use 50% of meal time doses with snacks)

protect from moisture; dispense in original container, do not refrigerate

CFTR modulators

increase the time the CFTR channels remain open, which increases the amount of CFTR delivered to the cell surface

genotype testing must be performed prior to initiating

most common mutation is a homozygous F508del mutation

CFTR modulator drugs

ivacaftor (kalydeco) --> not approved for use in homozygous F508del mutation (all other ones are)

lumacaftor/ivacaftor (orkambi)

tezacaftor/ivacaftor (symdeko)

elexacaftor/tezacaftor/ivacaftor (trikafta)

** take with high fat containing food

other concerns

a high-fat calorie dense diet is recommended

vitamin supplements required, especially fat-solube (A,D,E,K)

many patients will eventually require insulin for CF-related DM

TOBI podhaler counseling

do not swallow capsules

use only the provided podhaler device

take doses as close to 12 hours but no less than 6 hours apart

PEP counseling

take at the beginning of a meal or snack. take half of the meal time dose with snacks

swallow whole

contents can be sprinkled on a spoonful of soft food, use right away

do not mix with dairy products

drink plenty of non-caffeinated liquids everyday