Test 2 Respiratory-Elliot-Cystic Fibrosis-important stuff

The CF gene is found on chromosome __ and follows an autosomal ___ inheritance pattern

7, recessive

The CF gene codes for the CF-transmembrane conductance regulator (_____) protein

CFTR

the CFTR protein

-a membrane ion channel prevalent in secretory epithelial cells of airway, GI tract, sweat glands and GU system

-functions as a ___ channel

chloride

a dysfunctional CFTR protein due to a CF gene mutation will cause:

-____ Cl- secretion

-_____ Na+ reabsorption

decreased, increased

a dysfunctional CFTR protein due to a CF gene mutation will cause:

-altered ____ of fluid excreted by exocrine glands and ____ obstruction

viscosity, mucosal

Over 1,000 mutations exist of the CF gene, what is the most common one that causes 70% of cases?

F508 deletion mutation

what are the 3 early pathogens involved in early colonization of lungs in CF?

staphylococcus aureus, non-typable H-flue, psuedomona aeruginosa

what is the hallmark pathogen in CF?

psuedomona aeruginosa

what is replacement therapy treatment for pancreatic insufficiency in CF?

pancreatic enzyme replacement therapy (PERT)

pancreatic enzyme replacement therapy (PERT) products have:

1) ____- catalyze cleavage of fats

2) ____- catalyze breakdown of starches to sugars

3) ____- catalyzes the breakdown of proteins into amino acids

lipase, amylase, protease

dosing for PERT is based on amount of ____ per product

lipase

what is supplement treatment for pancreatic insufficiency in CF?

multivitamin with A, D, E, and K

what is the drug of choice for CF-related diabetes?

insulin

What is the gold standard for CF diagnosis?

the sweat test

The sweat test is based on 2 separate elevated ____ concentrations at ___ mmol/L or greater

Cl-, 60

if sweat test results are < ____ mmol/L, CF is unlikely

39

if sweat test results are ___-___ mmol/L, CF is possible

40-59

if sweat test results are >____ mmol/L, this is diagnostic of CF

60

Newborn screenings for CF test for the immunoreactive trypsinogen (____) level

IRT

____ levels of IRT in newborn screenings indicate CF; These tests screen for ___ only and a positive result requires referral

high, risk

non-pharm treatment of CF involves __ ___ ___ (ACT)

airway clearance techniques

Airway clearance techniques

__-__x per day for maintenance

___-__x per day for acute exacerbation

1-2, 3-4

______ should be used before or with ACT

bronchodilators

inhaled ___ should be used after ACT

antibiotics

A specific type of airway clearance techniques (ACT) is __ ___ ___ (CPT)

chest physical therapy

Chest physical therapy includes:

1) the ___ form- involves percussion (hitting your chest) and postural drainage (changing positions)

traditional

Chest physical therapy includes:

2) ___ ___ ___ ___ (PEP)- blow into device that vibrates

oscillating positive expiratory pressure

Chest physical therapy includes:

3) __ ___ ___ ___ (HFCC)-vibrating vest

High Frequency Chest Compression

Pharmacologic treatment for CF includes aerosolized antibiotics, which have activity against ___ ___

pseudomonas aeruginosa

Aerosolized antibiotics for CF treatment:

1) ________ (TOBI: comes in oral inhalation or podhaler)

2) ______ (aztreonam for inhalation)

3) _____

tobramycin, Cayston, Colistin

TOBI (tobramycin inhalation solution)

-works against gram ___ bacilli

-usual dosing is q12 hours, but this is reduced to once daily in patients with ___ ___

negative, renal impairment

TOBI (tobramycin inhalation solution)

-each dose takes about __-___ minutes to administer

15-20

TOBI (tobramycin inhalation solution)

-therapy is ___ days on, then __ days off

28, 28

TOBI (tobramycin inhalation solution) Adverse reactions

-______

-hoarseness

-______ (ringing in ears)

bronchospasm, tinnitus

TOBI (tobramycin inhalation solution)

-pregnancy category ___

D

TOBI (tobramycin inhalation solution)

-do not mix this with other drugs in a ____

nebulizer

TOBI Podhaler (DPI)

-each dose takes about __ minutes to administer (less time than TOBI nebulizer!-this was treatment breakthough)

5

administer Cayston (aztreonam for oral inhalation) by using only an ___ ____

altera nebulizer

administer Cayston (aztreonam for oral inhalation) TID:

-wait at least ____ hours between doses

-it takes ___-___ minutes per dose

4, 2-3

Cayston (aztreonam for oral inhalation):

-therapy is also ___ days on, then __ days off

28, 28

Cayston (aztreonam for oral inhalation) Adverse Reactions:

-____

-___ throat

-nasal congestion

-fever

bronchospasm, sore

Cayston (aztreonam for oral inhalation) Adverse Reactions:

-pregnancy category ___

B

Colistin (Colistimethate)

-____ formulation

-adverse effects include ___

aerosolized, bronchospasm

Since adverse effects for Colistin (Colistimethate) include bronchospasm, pretreat with a ____ and use immediately after reconstitution

SABA

Pharmacologic treatment for CF includes mucolytics, which decrease _____ of pulmonary secretions and increase sputum clearance

viscosity

mucolytics include _____ (dornase alpha) and _____ _____

pulmozyme, hypertonic saline

Pulmozyme (Dornase Alpha):

-is a deoxyribonuclease (DNA) ____ produced by recombinant technology

enzyme

The lungs of a patient with CF contain purulent airway secretions composed of highly polymerized ____, which produces a viscous mucus

DNA

Pulmozyme (Dornase Alpha):

-selectively cleaves ___ to reduce mucus viscosity

DNA

Hypertonic saline

-this is a ___% saline solution delivered via nebulizer

7

Pharmacologic treatment for CF includes ___-_____ agents:

-inhaled corticosteroids

-oral corticosteroids

-oral NSAIDs

-Azithromycin

-leukotriene modifiers

anti-inflammatory

Oral NSAIDs (Ibuprofen)

-must be dosed at high doses to inhibit ____ pathway leading to _____ neutrophil migration and lysosomal enzymes

lipoxygenase, decreased

if you were to use an Oral NSAID (Ibuprofen) at a low dose, this would ______ neutrophil migration and potentially increase ___ (which is bad)

increase, inflammation

Pharmacologic treatment for CF includes ___ ____ ___, which was a treatment breakthrough because it does not just control symptoms, but works on the underlying pathophysiology of CF

CFTR modulator therapies

A CFTR potentiator treatment is ___ (Kalydeco)

ivacaftor

Ivacaftor (Kalydeco)

-increases CFTR transport function

-potentiates epithelial cell Cl- ion transport of defective ___ CF gene mutations cell-surface CFTR protein

97

Ivacaftor (Kalydeco)

-is indicated for patients 1 ____ and older who have __ mutation in the CFTR gene that is responsive

month, 1

remember- Ivacaftor (Kalydeco) is a ____ (increases CFTR transporter function so Cl- can move through)

potentiatior

Ivacaftor is a potentiator (increases CFTR transporter function so Cl- can move through), but treatment for CF also requires a ____ component (to move the CFTR to cell surface)

corrector

since Ivacaftor is only a potentiator, we can use ____/____ (Orkambi) that has both corrector and potentiator function

lumacaftor/ivacaftor

MOA of Lumacaftor (the corrector):

-improves conformational stability of F508del-CFTR

-results in increased processing and trafficking of mature protein to the __ ___

cell surface

lumacaftor/ivacaftor (Orkambi)

-is indicated for patients 1 ___ and older who are homozygous for the ____ deletion mutation in the CFTR gene

year, F508

another CFTR modulator therapy that has both corrector and potentiator function is ____/____ (Symdeko)

tezacaftor/ivacaftor

MOA of Tezacaftor (the corrector):

-facilitates cellular processing and trafficking of normal and select mutatnt forms of CFTR to increase the amount of mature CFTR protein delivered to ___ ___

cell surface

tezacaftor/ivacaftor (Symdeko)

-is indicated for patients ___ years and older who are homozygous for the F508 deletion mutation in the CFTR gene

OR

-indicated for patients that have at least 1 mutation in the CFTR gene that is ___ to tezacaftor/ivacaftor

6, responsive

all CFTR modulators require:

-administration with high ___ containing foods

-avoiding grapefruit and seville oranges

-dosage adjustments in patients with hepatic impairment and with concomitant use of ___ inhibitors

fat, CYP3A4

another CFTR modulator therapy that has both corrector and potentiator function is ____/___/___ (Trikafta)

elaxacaftor/ivacaftor/tezacaftor

Ivacaftor functions as a potentiator, while Elaxacaftor and Tezacaftor are both ____

corrrectors

elaxacaftor/ivacaftor/tezacaftor (Trikafta)

-is indicated for patients ___ years and older who are homozygous for the F508 deletion mutation in the CFTR gene

OR

-indicated for patients that have at least 1 mutation in the CFTR gene that is ___ to tezacaftor/ivacaftor

2, responsive

summary of what genotype can take each CFTR

Ivacaftor-1 mutation responsive

Lumacaftor+Ivacaftor-_____ for F508del (2 copies)

Tezacaftor+Ivacaftor -______ for F508del (2 copies) OR 1 mutation responsive

Elaxacaftor+Tezacaftor+Ivacaftor- at least 1 copy of F508del OR 1 mutation responsive

homozygous, homozygous

What order should CF patients administer medications?

step 1: open airways/prevent bronchospasm with a ______

SABA

What order should CF patients administer medications?

step 2: clear mucus with _____

mucolytics

What order should CF patients administer medications?

step 3: treat pseudomonas with an ___ ____

inhaled antibiotic

if a patient needed an ICS, it would be administered before the ___ ____

inhaled antibiotic

During treatment of pulmonary exacerbations, continue chronic medications and airway clearance (but increase to __-___x per day)

3-4

treatment for mild symptoms of pulmonary exacerbations include oral and inhaled outpatient antibiotic treatment for __-___ days

14-21

treatment for severe infections in pulmonary exacerbations includes IV antibiotic treatment for 2-3 weeks, including anti-pseudomonal ___-____ and _____ for synergy and delayed resistance

beta-lactam, aminoglycoside

PK monitoring is ____ (critical!!) in CF patients

required