Cystic Fibrosis Therapeutics

Non pharm tx of cystic fibrosis

Exercise

Chest drainage

chest therapy

nutrition

Pharm tx of cystic fib

Pancreatic enzymes

anti effective tx

Maintence=

• Inhaled antibiotics

• dornase alpha

• mucolytics/bronchodilators

• corticosteroids

CTDR modulators

Leading cause of Cys fib

Mutation of Class 2 protein

What happens due to endobronchial infection and how to tx

Hypermetabolic state

provide calories at 120-200% of RDA and high fat and protein diet

Which drugs are appetite stimulants

Cyproheptadine

Dronabinol

2 multivitamins

Which drugs are pancreatic enzymes

Creon

Pertyze

Zenpep

Which pancreatic enzymes can be switched

Creon

Pancreaze

Where is pancreas enzymes dissoluted

alkaline ph

small intesitine

What to monitor when taking pancreatic enzymes

Height weight

number of stools/day

Which immunizations reccomended for cys fib

PPSV23

What are the pulmonary complications of cys fib

Acumulation of mucus and plugging of airways

Which drugs are clear airways

B2 agonists for asthma

Mucolytics= pulmozyme, hypertonic saline, mannitol

Antibiotics= azithromyicin and inhaled abx

What is the role of pulmozyme

degrades polymerized DNA from dead and dying neutrophils

What is the role of hypertonic saline and mannitol

mucus hydrators

What is pulmozyme indicated for

Lung disease from CF

MOA of hypertonic saline

Creates an osmotic gradient drawing water into airway and rehydrating. Lowers mucus viscoxity

What is TOBI indicated for

CF pts with mod-severe lung disease

Which drugs are aerolized abx

Bekhia

Kitabis

TOBI

When do u see improvement after tobi

after 2 weeks up to 12 weeks

What is Axtreonam indicated for

Pseudomonase aerunginosa chronic infection

What are the effects of azithromycin

Inhibit neutrophil migratin and reduce proinflammatory mediatores

What must u test for before staeting azithromycin

Non Tv myobacterium

AE of azithromycin

resistance to non TB infection

QT prolongation

Role of Ibuprofen

For FEv1 > 60%

Reduced neutrophil migration and function and decline in lung function

For pulmonary exacerbations that are staph non MRSA what to use

Nafcillin, Oxacillin, Dicloxacillin, Amoxicillin-

clavulanate, Clindamycin with Ag, Extended-

spectrum penicillins, Cephalosporins,

Macrolides, TMP/SMX

For MRSA exacerbations which meds

Vancomycin or linezolid (myelosuppression) or

ceftaroline (Q8), or clindamycin

For Pulmonary exacerbation of burkholderia cepacia

ceftazidime or TMP/SMX, or

meropenem

S.maltophilia tx

TMP/SMX

doxycycline

Tx of pseudomonas aeruginosa

Recommended: double coverage (beta-lactam + amino glycoside)

• Cephalosporins with anti-pseudomonal coverage

• Aminoglycosides once daily

• Carbapenems with anti-pseudomonal coverage

• Aztreonam

• Fluoroquinolones

• Colistimet`

How to treat allergicbronchopulmonary aspergillosis

Rx systemic corticosteroids +/- itraconazole or voriconazole

• Itraconazole 5 mg/kg/day divided bid (max 200/dose)

• Oral solution 10 mg/ml improved BA as compared to solid dosage

forms. Give on empty stomach

• Capsules requires food with administration

• Voriconazole: less well studied, higher hepatotoxicity in pediatric

pts

How long do u use abx in pulmonary exacerbations

10-14 days

What does corrector CFTR modulator do

Improves quality of CFTR that will be delivered to cell

surface

What does potentiator CFTR modulator do

improves opening of the CFTR protein channel

What does amplifier CFTR modulator do

Increase amount of CFTR mRNA (and protein) within the cell

MOA od Ivacaftor

Targers Gate mutations- class 3

Potentiator

Binds to defective protein at cell surface, opens mutant CFTR channel and augments activity of protein at plasma membrane

improves lung function and activity of protein

What must IVacaftor be taken with

High fat foods

AE of IVacaftor

Dizziness

Dermatologic

Hypglycemia

Increased LFTs

What is the role of Lumacaftor plus Ivacaftor

Correct F508del

Lumacaftor that corrects misfolding

Ivacaftor augments fating function and ion conductance

FEV1 improvement

AE of Lumacaftor/ Ivacaftor

Chest tightness

eleveation is transaminases and total serum billiribin

Tezacaftor/ivacaftor role

Teva=corrector

imrpves CFTR procession, trafficing and CL transport

less AE

What is Trikafta:

Elexacaftor (corrector)–

Tezacaftor (corrector)

–Ivacaftor (potentiator)

MOA of Trikafta

estores Phe508del CFTR protein function by improving processing

and trafficking to very high levels

• Presents greater amount of CFTR protein at cell surface

AE of Trikafta

cough, hemoptysis, fever, cataracts (eye exam baseline and yearly)

Role of Alyftrex-Vanzacaftor/tezacaftor/deutivacaftor

Increased quantity and function of CFTR at the cell surface, resulting in increased CFTR activity

AE of Alyftrek

• Drug-induced liver injury and failure: monitor closely

• Hypersensitivity, including patients who developed this reaction with Trikafta

• Cataracts

How long do you take CFTr therapy

Continued for life