Pharmacotherapy III: Cystic Fibrosis

CF (cystic fibrosis)

A genetic condition caused by a mutation in the gene that encodes for the CFTR protein.

secretory epithelial cells

Where are CFTR proteins found?

move Cl ions outside the cell

What is the role of CFTR proteins?

lungs, sweat glands, pancreas, GI/GU

Since CFTR proteins are found on secretory epithelial cells, their dysfunction may affect these organ systems.

water

Where Na and Cl go, _________ follows.

water

If a CFTR protein is dysfunctional and Cl cannot leave the epithelial cells in the lungs, the lungs become clogged with _____.

A, C, D

What are some consequences of water being stuck in the lungs? SATA.

(a) impaired mucociliary clearance

(b) impaired deep cough reflex

(c) colonization of the fluid by bacteria

(d) fibrosis of the lungs

A, B, C

What are some of the consequences of water being stuck in the pancreas? SATA.

(a) development of diabetes

(b) digestive enzymes cannot reach the duodenum

(c) weight loss, malnourishment, and poor growth

(d) poor metabolism of many drugs

sweat testing, newborn screening, fecal elastase assessment

What three routine tests can we perform to evaluate for CF?

sweat test

A test that measures how much Cl is present in a patient's sweat.

60

Cl levels > ____ mmol/L are diagnostic for CF.

newborn screening

A heelstick test performed 24-48 hours after birth followed by an IRT assay.

F

T or F: Heelstick testing in infants is reliable and is usually definitive for all mutations of CF.

fecal elastase test

A test used to identify if CF is causing pancreatic insufficiency.

200

Fecal elastase levels below ______ indicate pancreatic insufficiency.

pulmonary maintenance, pulmonary exacerbations

What are the two main pulmonary treatment guidelines for CF?

pancreas

What other organ system requires treatment in CF patients?

albuterol, hypertonic saline, dornase alfa (in that order)

What drugs can we use to relieve mucus obstruction in pulmonary CF maintenance treatments?

all ages

Who is a candidate for albuterol administration for mucus obstruction?

prevents bronchospasm from the other medications

Why is albuterol given for mucus obstruction?

hypertonic saline

The drug often given after albuterol to improve CF lung function.

6

Patients must be ___ or older to receive hypertonic saline treatment.

dornase alfa

A third drug administered after hypertonic saline to improve lung function in CF.

5

Patients must be ___ or older to receive dornase alfa.

airway clearance exercises

After all 3 medications are administered for mucus obstruction, _____________ are needed to physically remove the mucus.

oscillating vests, chest percussion, huffing/coughing exercises

What are some preferred airway clearance exercises to physically remove mucus?

Azithromycin

If the patient has a history of chronic pseudomonas and has a risk of biofilm formation, they should receive this medication 3x weekly for prevention.

6

Patients must be ___ or older to receive Azithromycin for inflammation control and pseudomonas biofilm destruction.

Tobramycin nebulizer

If a CF patient has a positive culture, which antibiotic is preferred for infections?

Aztreonam nebulized

What other antibiotic can be used for spontaneous infections in CF?

Tobramycin

Which antibiotic can be used for both ERADICATION and suppression?

6

Tobramycin can be used in patients ___ years and older.

7

Aztreonam can be used in patients ___ years and older.

28

If the goal of antibiotic therapy is eradication, antibiotics will be given for a ___-day course.

28-day cycle

If the patient requires continuous suppression by antibiotics, they should receive it as a...

worsening cough, sputum, or decline in FEV1

What would classify a CF patient as experiencing a pulmonary exacerbation?

increase albuertol 4x qd, dornase alfa increased BID

How should we change their maintenance airway therapies during an exacerbation?

use double pseudomonas therapy

How should we change their antibiotic therapy during a pulmonary exacerbation?

PSA-b-lactam + aminoglycoside

What antibiotic regimen is recommended for double coverage during a pulmonary exacerbation?

increased, higher

In CF patients, particularly pediatrics, Vd is usually ___________ and _______ doses may be needed.

increased, more frequent

In CF patients, particularly pediatrics, Cl is usually ________ and ________ dosing may be required.

high-calorie, high-fat

What diet is preferred in CF patients?

fat-soluble vitamins, cholecalciferol

What needs to be supplemented in a CF patient's diet?

Vitamin D

Cholecalciferol is another name for __________.

30

Cholecalciferol levels should be maintained above ____ ng/mL.

PERT (pancreatic enzyme replacement therapy)

The mainstay of pancreatic treatment in CF patients is the use of _________ therapy.

amylase, protease

What enzymes are administered via PERT?

microencapsulated EC forms

Which formulations of PERT are preferrable?

every meal and snack, feeds in infants

When should PERT be administered?

insulin, exercise

What therapies are preferred in CF-related diabetes?

10yo

When do we start screening for CF-induced diabetes?

OGTT (oral glucose tolerance test)

Which test do we use to screen patients for diabetes?

FBG (> 126)

Which lab value is preferred in diabetes diagnosis for CF patients?

BG checks TID, quarterly A1C, lipids annually

What monitoring should be done for CF-related diabetes?

CFTR modulators

Newer CF therapies that aim to address the cause of CF, not just treat the symptoms.

5

How many types of CFTR mutations are there?

nonfunctional protein

What is a class I CFTR mutation?

processing mutation (right protein, wrong place)

What is a class II CFTR mutation?

gating mutation (channels don't open properly!)

What is a class III CFTR mutation?

conduction mutation (channels are dysfunctional)

What is a class IV CFTR mutation?

not enough CFTR produced

What is a class V CFTR mutation?

class I

Which mutation type is typically considered the most severe?

Ivacaftor

A potentiator-type CFTR modulator that works by increasing the function of already-existing CFTR channels on the cell surface.

I or II

Which defects can Ivacaftor NOT be used for since it requires CFTR to be properly synthesized and transported?

Lumacaftor, Tezacaftor

2 corrector-type CFTR modulators used to correct misfolded proteins and increase processing and trafficking to the right place.

T

T or F: Correctors must always be used with potentiators (Ivacaftor).

class II

Lumacaftor is often added to Ivacaftor to cover these types of mutations.

Lumacaftor

Which corrector is a major 3A4 substrate as well as inducer?

Tezacaftor

Which corrected is a major 3A4 substrate, but has less interactions and is NOT an inducer?

Lumacaftor

Which corrector may have side effects such as chest tightness?

Trikafta, Alyftrek

Two triple therapy CFTR modulators that can cover a wide range of mutations with excellent efficacy.

Trikafta

Triple therapy is approved for ages ___ and up.

Alyftrek

Which triple therapy has once daily dosing?

A, C, D

How should CFTR modulators be taken? SATA.

(a) take with high-fat snack or meal

(b) take on an empty stomach

(c) powder can be mixed with room temperature soft food or liquid

(d) entire dose must be taken within 1 hour of mixing

cataracts, hepatotoxicity, CNS effects, skin rash, ICP, arthralgia

What are some adverse effects of CFTR modulator use?

3A4

All CFTR modulators are MAJOR substrates for ___!!!

annual eye exam (cataracts), LFTs at baseline then q3 months

What needs to be monitored while on CFTR modulators?