Exam 5 - Cystic Fibrosis Flashcards
Autosomal (dominant or recessive) genetic disease
recessive
CF is caused by a mutation in a gene that encodes for the _____________ protein
cystic fibrosis transmembrane conductance regulator (CFTR)
what does ENaC stand for
epithelial sodium channel
Presenting Signs and Symptoms in Neonates?
Meconium ileus (1st bowel movement gets stuck) Prolonged obstructive jaundice
Presenting Signs and Symptoms in infants and children?
Cough, recurrent URI, wheezing
Failure to thrive (gain weight)
Heat intolerance
Presenting Signs and Symptoms in adolescentes/adults?
delayed sexual maturation
nasal polyposis
most common mutation in CF?
delta F508
pathophys/results from CFTR mutations?
if CFTR is wack — chloride will not get into mucus = neither will sodium – since water follows sodium - water does not get into mucus = mucus is dehydrated and hard to get out of the body/lungs
How to do a newborn screen?
get blood from their heel – its an IRT test (immunoreactive trypsinogen)
if positive for CF — still need further workup for a diagnosis
For diagnosis fo CF:
need at least ______ sign/symptom + evidence of ______
1 sign or symptom
what are some tests for CF?
sweat chloride test – gold standard
genetic testing
pancreatic function tests
what pancreatic function tests can be done to see if CF is happening
stool fat quantitation
quantitation of trypsin activity
how does the sweat test work?
they give pilocarpine and make a part of your body sweat – and measure the chloride concentration
what is a positive sweat test?
> 60 mEq/L of chloride in the sweat
Ivacaftor/Kalydeco: what class of drug is it?
CFTR potentiator: helps “open the gate”
Ivacaftor/Kalydeco:
Counseling points?
take with fatty food to help absorption
Ivacaftor/Kalydeco:
monitoring?
LFTs Q3months x 1 yr
eye exam - baseline and yearly
Ivacaftor/Kalydeco:
drug interactions?
CYP3A substrate (dont forget grapefruit!)
Orkambi – what are the generic drugs in it?
ivacaftor/lumacaftor
Orkambi:ivacaftor/lumacaftor:
have to have what mutation?
HOMOZYGOUS delta F508
Orkambi:ivacaftor/lumacaftor:
counseling?
take with fatty foods
hormonal birth control will not be effectice
Orkambi:ivacaftor/lumacaftor:
drug interactions?
hormonal birth control is ineffective
also ivacaftor = 3A substrate
lumacaftor = 3A inducer
Orkambi:ivacaftor/lumacaftor:
monitoring?
AST/ALT/Bil q3month for 1 year and then yearly
Eye exam baseline and then yearly - peds
Kalydeco or Orkambi has higher increase in FEV1 and why ever use the other one?
Kalydeco has the MUCH better FEV1 increase
use Orkambi when HOMOZYGOUS F508 — that genotype is NOT approved in kalydeco (hence why it is used)
Symdeko – generic drugs in it?
tezacaftor/ivacaftor
Symdeko:tezacaftor/ivacaftor:
counseling?
take with fatty foods
two diff tabs taken: 1 in AM is combo pill; evening pill is just ivacaftor
Symdeko:tezacaftor/ivacaftor:
monitoring?
AST/ALT/Bil q3month for 1 year and then yearly
Eye exam baseline and yearly - pediatrics
Dose adjustment for liver disease
Kalydeco, Orkambi or Symdeko:
is approved for only 12 above right now
symdeko
Kalydeco, Orkambi or Symdeko:
are used in CF why?
“to fix the basic defect” the CFTR problem
Kalydeco, Orkambi or Symdeko:
which one can cause chest tightness
Orkambi
why Symdeko is good – less chest tightness
Kalydeco, Orkambi or Symdeko:
can cause weight gain
orkambi – GOOD side effect with CF pts
CF pathophys/presentation:
common things to happen in the “head region”?
nasal polyps
allergy symptoms
psychological - depression
how to treat/manage nasal polyps for CF pts?
sinus surgery
nasal steroids
saline nasal rinses
gentamicin nasal rinses
how to treat/manage allergies for CF pts?
nasal steroids!
avoid antihistamines if possible – dont want to dry their mucus out anymore!!
how to treat/manage depression for CF pts?
SSRIs (avoid any wt loss causing ones)
Mirtazipine is great because it causes appetite stimulation
CF pts and pulmonary:
why are they at a high risk of lung problems?
the dehydrated mucus that doesn’t get cleared easily creates a wonderful environment for bacteria to grow
this cycle of infection/inflammation/tissue damage – will overall lead to decrease lung function
For all CF pts - “airway clearance” is recommended – what are the different options that can be used?
manual clearance techniques (banging on the kids chest to loosen mucus) therapy vest flutter/acapella machine huff coughing (?) meta neb (?)
drugs that can be used for maintenance lung treatment?
nebulized drugs:
anti-inflammatory:
bronchodilator:
nebulized drugs:dornase alfa / hypertonic saline
anti-inflamm drugs: azithromycin and ibuprofen
bronchodilator: albuterol
MOA of dornase alfa?
cleaves extracellular DNA from expended neutrophils/other inflamm cells in CF mucus = reduces viscosity and promotes clearance!!
MOA of hypertonic saline is somewhat unknown — but what is the proposed MOA?
NaCl in airway creates osmotic gradient = water drawn into airway/makes mucus thinner = easier to expectorate
Dornase alfa and hypertonic saline recommended in CF pts if above age of _____
6 years old
what drugs that are normally helpful lung function things should NOT be used in CF?
NO inhaled corticosteroids
NO leukotriene modifiers (montelukast)
NO ipratropium because it is DRYING
NO oral corticosteroids
If CF lung exacerbation:
want to cover pathogens — if MRSA
how many drugs needed and what are the options?
just 1 drug needed bactrim clindamycin vanc tetracycline linezolid
If CF lung exacerbation:
want to cover pathogens — if MSSA
how many drugs needed and what are the options?
just one drug needed
cefazolin
unasyn
a antipseudomonal beta lactam that covers MSSA is good too….
If CF lung exacerbation:
want to cover pathogens — if pseudomonas
how many drugs needed and what are the options?
TWO DRUGS!!
have a beta lactam that covers pseudomonas PLUS an aminoglycoside
what aminoglycoside is not recommended for CF/pseudomonas coverage
gentamicin
Abx in CF pts can act a little different:
beta lactams are affected how and what should we do about it?
there is augmented/higher renal clearance – increase the dose at shortest interval
Abx in CF pts can act a little different:
aminoglycosides are affected how and what should we do about it?
increase Cl and Vd (harder to penetrate the lungs!)
do an initial dose of 10 -12 mg/kg Q 24h
Abx in CF pts can act a little different:
beta lactams should be infused how to help the PK changes?
infuse for LONGER; (like over 4 hours)
infusing longer = can do a higher dose with less toxicity issues
Abx monitoring for CF pts?
pulmonary function tests O2 Sat serum drug concentrations Q3-5 days AG PK dose adjustments via peak/trough SCr Q3-5
what are some options for inhaled abx for CF pts
tobramycin**
aztreonam**
amikacin
colistin
**ones she talked about the most
inhaled tobramycin can be used for what two main things in CF pts?
for INITIAL pseudomonas eradication - one 28 day course
OR
suppression therapy for pts with CHRONIC pseudomonas (in 28 day cycles)
inhaled aztreonam is used when in CF pts?
only for SUPPRESSION/chronic pseudomonas – use in alternating months with tobramycin
inhaled tobramycin or inhaled aztreonam:
which one is more often (TID) but shorter administration time overall?
aztreonam
inhaled tobramycin or inhaled aztreonam:
which one is BID and administered for 15 - 20 minutes at a time
tobra
inhaled tobramycin or inhaled aztreonam:
which one causes a cough and why?
tobra – because it is a powder
benefits of nebulization?
- delivery of the drug to the site of infection
- reduced systemic exposure
- decrease risk of systemic side effects
- route allows for chronic admin of antipseudomonal abx without IV
- ability to get high concentrations of the drug to the site
what does ABPA stand for
allergic bronchopulmonary aspergillosis
how to treat ABPA
prednisone burst then taper
and then use an antifungal that covers aspergillus (voriconazole, itraconazole, posaconazole)
what are the possible liver issues that come CF?
focal biliary cirrhosis (biliary obstruction/progressive periportal fibrosis)
liver steatosis
liver failure
pancreatic issues in CF?
mucus obstructs exocrine ducts decreased enzymes (amylase/lipase/protease) decrease HCO3 output
Pancreatic enzymes:
typical starting dose?
usually 1000 units of lipase/kg/meal
Pancreatic enzymes:
do not exceed ______ units of lipase/kg/day
10,000
Pancreatic enzymes are adjust based on what things>
of stools per day
fat content of stools
and growth/weight
want to supplement what kind of vitamins?
fat soluble (ADEK)
supplement want kind of minerals?
Ca2+
iron
SODIUM!! they loose so much in their sweat
what are some drugs that can be used as an appetite stimulant
cyproheptadine
mirtazapine
dronabinal
