Pulmonary Flashcards
What is the definition of cystic fibrosis?
dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR)
What is the most common life-limiting genetic disorder in caucasians?
Cystic fibrosis
What organ systems are affected by cystic fibrosis?
lungs
digestive system
reproductive system
What is the most common mutation in the CFTR gene?
F508del
Cystic fibrosis is an autosomal __ disease
recessive
__ occurs in the distal airways of the lung and submucosal glands that express CFTR
Mucosal obstruction
CFTR regulates __ across the cell membrane
chloride transport
CFTR helps regulate ion transport and __ homeostasis
salt
What is the effect go a CF gene defect in the lungs?
decreased airway surface liquid
colliery collapse and decreased mucocilliary transport
CF in the lungs is a vicious cycle of mucus retention, infection, and __
inflammation
What class of mutation is categorized by no traffic?
Class II
What is the presentation of CF in the sinus and pulmonary systems?
chronic infections and nasal polyps
SOB and cough with sputum production daily
flat diaphragm
decreased FEV1
digital clubbing from chronic hypoxia
What is the presentation of CF in the GI system?
pancreatic insufficiency
meconium ileum, steatorrhea, and failure to thrive due to malabsorption
older patients: severe constipation and insulin deficiency
What is the presentation of CF in the male reproductive system?
Azoospermia
What is the presentation of CF in the female reproductive system?
Decreased fertility
T or F: all states require CF newborn screening
True
What two tests are used to diagnose CF?
Immunoreactive trypsinogen (IRT) screening test
Quantitative pilocarpine iontophoresis sweat test (QPIT) (or sweat chloride test)
What is a diagnostic level of chloride content when using the QPIT?
> 60 mmol/L
What is nonpharmacologic therapy for CF?
Adults: normal weight
Pediatrics: normal growth
Require 110-200% energy take
What medication is used to treat nutrient malabsorption due to pancreatic insufficiency?
Pancrelipase
What is a typical dose for pancrelipase?
500-2500 lipase units/kg/meal
What can happen if the patient takes too much pancrelipase?
Colonic strictures
What are risk factors for pancrelipase-induced colonic strictures?
<12 years old
>6000 lipas units/kg/meal for >6 months
history of meconium ileus
history of intestinal surgery
IBS
When should colonic stricture be considered?
evidence of obstruction
bloody diarrhea
abdominal pain
poor weight gain
What formulations does pancrelipase come in?
Capsules with enteric coated microspheres
Enteric coated tablets
What are risk factors for bone disease in CF patients?
malabsorption of vitamin D
poor nutritional status
physical inactivity
glucocorticoid therapy
antibiotics that require protection from sunlight exposure
What vitamins are fat soluble?
A, D, E, K
What is a goal vitamin D level?
> /=30 ng/mL
What test should be obtained for all adults that is related to bone health and vitamin supplementation?
Dual x-ray absorptiometry (DXA)
In a CF patient, what is the protocol is the T/Z score is >/= -1.0?
Optimize vitamin D, calcium, and vitamin K supplementation
Repeat in 5 years
In a CF patient, what is the protocol is the T/Z score is > -2.0
Aggressive infection treatment, minimize steroid dosing, treat CF-related diabetes
Repeat in 2-4 years
In a CF patient, what is the protocol is the T/Z score is </= -2.0?
Consider bisphosphonate
Repeat annually
When should airway clearance therapy be initiated in a CF patient?
within the first few months of life
What are the different examples of chest percussion?
Cupped hand pounding
Percussion vest
Aerobic exercise
What is the order of clearance therapy for patients with CF receiving chest percussion?
Bronchodilator
Hypertonic saline
Dornase alfa
Aerosolized antibiotic
What are examples of aerosolized antibiotics?
aztreonam
tobramycin
What are examples of anti-inflammatory drugs used in CF patients?
high-dose ibuprofen (20-30 mg/kg BID)
azithromycin
What bacteria is found in the early stages of CF?
staphylococcus aureus
What bacteria is found in the later stages of CF?
pseudomonas aeruginosa
What is the treatment of stenotrophomonas in CF patients?
Bactrim or doxycyline
T or F: Cf patients have larger volumes of distribution and slower clearance.
False
larger Vd
faster clearance
May need larger doses at shorter intervals
What vaccinations should CF patients get?
annual flu vaccine
Pneumonia
Covid
When does CF related diabetes usually present?
18-21 years
What is the therapy of choice in patients with CF related diabetes?
insulin
What is the indication for Ivacaftor (Kalydeco)?
Class III mutation
at least 1 month
What is the indication for Lumacaftor/Ivacaftor (Orkambi)?
Homozygous F508del
at least 1 year
What is the indication for Tezacaftor/Ivacaftor (Symdeko)?
Homozygous F508del
at least 6 years
What is the indication for Elexacafotr/Tezecaftor/Ivacaftor (Trikafta)?
at least one F508del mutation
at least 2 years
Increased oxygen uptake, blood volume, and cardiac output in pregnancy of a CF patient may lead to what complication?
right-sided heart failure
CF candidates for transplant are those with a FEV1 < __
30%
When should CF patients follow up with their provider?
every 1-3 months
What causes the increased mucus viscosity in CF patients?
Cl- is trapped in the cells, so no sodium or water moves out in to the lung mucus
What CF medication is a potentiator?
Ivacaftor
What CF medications are correctors?
Lumacaftor
Tezacaftor
Elexacaftor
Most CF medications have ___ absorption with fatty food
increased
The Cf medications are metabolized by __
CYP3A4/5
CFTR is a __-activated anion (CL-) channel
cAMP
What is the mechanism of action of Ivacaftor?
It binds to the defective protein at the cell surface and opens the chloride channel
What is the mechanism of action of Lumacaftor?
It corrects the processing and trafficking of defected CFTR protein
What are side effects of CFTR modulators?
headache, dizziness, skin rash, abdominal pain, diarrhea, nausea, nasal congestion, oropharyngeal pain, upper respiratory tract infection, nasopharyngitis
What are DDIs with CFTR modulators?
CYP3A4 inhibitors (Cimetidine, fluconazole, ketoconazole, grapefruit juice)
How is dornase alfa administered?
inhalation
What is the source of dornase alfa?
recombinant human DNase I
What are side effects of dornase alfa?
chest paine, voice disorder, cough, pharyngitis, rhinitis, skin rash, dyspnea
What is the mechanism of action of dornase alfa?
hydrolyzes the DNA of mucus in CF patients to decrease mucus viscosity
What is the source of pancrelipase?
contains a combination of lipase, amylase, and proteases
natural product from porcine pancreatic glands
What are side effects of pancrelipase?
headache, neck pain, abdominal pain, nasal congestion
What are examples of methylxanthines?
theophylline
caffeine
Theophylline has a __ therapeutic index
narrow
T or F: Theophylline has significant first pass metabolism
False
What enzyme metabolizes theophylline?
CYP1A2
A high fat meal __ absorption of theophylline
decreases
Increased cAMP causes __
bronchodilation
Increased cGMP causes __
decreased inflammatory cells
Theophylline is a __ PDE inhibitor
non-selective
Theophylline block the __ receptor and causes increased heart rate and vasoconstriction
adenosine
What medications decrease clearance of theophylline?
Cimetidine, macrolides, allopurinol, propranolol, quinolones
What medications increase clearance of theophylline?
Carbamazepine, phenytoin, moricizine
Smokers have __ clearance
increased
What are side effects of theophylline at lower concentrations?
headache, nausea, vomiting, insomnia
What are side effects of theophylline at higher concentrations?
arrhythmias, seizures, death
The side effects of theophylline at higher concentrations are due to __ effects.
adenosine
Roflumilast is metabolized by __ and __
CYP 3A4 and 1A2
Roflimulast is a __ PDE inhibitor
selective
What is the mechanism of action of roflimulast?
inhibition of PDE4
increases cAMP levels
Decrease inflammatory cells and cytokines, decrease bronchoconstriction, decrease vascular permeability
What are side effects of rolflimulast?
headache, insomnia, anxiety, depression, decreased appetite, weight loss, nausea, diarrhea, abdominal pain
Does roflumilast antagonize the adenosine system?
no
What medications decrease roflumilast concentrations?
CYP3A4 inducers (rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, St John’s wort)
What is the definition of chronic bronchitis?
chronic or recurrent excessive mucus secretion with cough
Present on most days for at least 3 months of the year
What is the definition of emphysema?
Destruction of alveoli
No obvious fibrosis
What are possible etiologies of COPD?
smoking
occupational exposures
environmental air pollution
alpha antitrypsin (AAT)
Asthma and airway hyperresponsiveness are risk factors
recurrent infections increase risk
What are the three components of the mechanistic triad of COPD?
inflammation
imbalance between proteases and antiproteases
oxidative stress
In the central airways, inflammatory cells and mediators stimulate __
mucus-secreting gland hyperplasia
mucus hypersecretion
What is the major site of airflow obstruction in COPD?
peripheral airways
Advance COPD can lead to __
hypoxemia
hypercapnia
What is hypercapnia
abnormally elevated carbon dioxide levels in the blood
Pulmonary hypertension in a COPD patient can lead to __
cor pulmonale (right-sided heart failure)
COPD patients can get progressive loss of __ muscle
skeletal
What are symptoms of COPD?
variable onset
Do not correlate with severity of airflow limitation
chronic cough (>3 months)
chronic sputum production
dyspnea on exertion
as disease progresses: dyspnea at rest, ability to perform daily tasks declines
What are signs of COPD?
use of accessory muscles
pursed-lips breathing
increased respiratory rate
shallow breathing
hyperinflation of chest
auscultation: distant breath sounds, wheezing, rhonchi
Advanced: cyanosis, tachycardia
Cor pulmonale: lower extremity edema, hepatomegaly, JVD
What are laboratory tests for COPD?
polycythemia: elevated hematocrit
If FEV1 <35%, or s/sx of cor pulmonale, check pulse oximetry
If O2 sat <92%, check ABG
AAT level if <45 year and presenting with COPD s/sx, especially with FH of emphysema
Post bronchodilator FEV1/FVC < __ confirms presence of persistent airflow limitation
70%
What is a GOLD1 classification?
mild
FEV >/=80& predicted
What is GOLD2 classification?
moderate
FEV1 50-80% predicted
What is GOLD3 classification?
severe
FEV1 30-50% predicted
What is GOLD4 classification?
very severe
FEV1 <30% predicted
What two tests are sued to assess symptoms in COPD patients?
mMRC
CAT
How is a COPD patient classified as E?
> /=2 moderate exacerbations or >/=1 leading to hospitalization
How is a COPD patient classified as A?
0 or 1 moderate exacerbations not leading to hospitalization
AND CAT <10
How is a COPD patients classified as B?
0 or 1 moderated exacerbations not leading ti hospitalization
AND CAT >/= 10
What are the desired outcomes of treating a COPD patient?
reduce symptoms
reduce risk
smoking cessation
What is the green zone for a COPD patient?
usual activity level
usual amount of phlegm/mucus
take daily medications
What is the yellow zone for a COPD patient?
more breathless than usual
more coughing and increased phlegm/mucus production
continue daily medications and add reliever inhaler, oral corticosteroids, and/or antibiotic
What is the red zone for a COPD patient?
severe SOB, even at rest
coughing up blood
call 911 or seek immediate medical care
What is the only intervention to slow disease progression and long-term FEV1 decline?
smoking cessation
What immunizations should COPD patients get?
annual flu vaccine
pneumonia vaccine
Tdap
Covid
What are the components of pulmonary rehabilitation?
exercise training
breathing techniques
education
psychological and nutritional counseling
Optimum benefit is achieved with a pulmonary rehabilitation program lasting __
6-8 weeks
When should COPD patients do pulmonary rehabilitation?
at diagnosis
hospital discharge following an exacerbation
progressively deteriorating symptoms
What is the mainstay of treatment for symptomatic COPD?
bronchodilators
What are SABA key points in COPD?
rescue therapy for acute relief
avoid continuous, daily therapy
What are LABA key points in COPD?
decrease COPD exacerbations and improve exercise intolerance, dyspnea, and quality of life
patients should also receive a SABA prn
What are examples of combination bronchodilator products?
albuterol/ipratropium (Combivent)
Vilanterol/umeclidinium (Anoro)
What is the indication for theophylline?
patients who cannot use inhaled medications or are symptomatic despite appropriate use of inhaled bronchodilators
What is the target concentration for theophylline in COPD patients?
5-15 mg/L
What conditions increase concentrations of theophylline?
heart failure
liver disease
What conditions decrease concentrations of theophylline?
high protein diet
Theophylline should be dosed based on __
IBW
When converting from aminophylline to theophylline you __
multiply by 0.8
When converting from theophylline to aminophylline you __
divide by 0.8
Theophylline has __ kinetics
non-linear
What are key points for corticosteroids in COPD?
monotherapy is not recommended
avoid long-term use of oral corticosteroids
When is rolflumilast indicated?
severe or very severe COPD and a history of exacerbations
What is the onset for rolflumilast?
4 weeks
What is in Trelegy Ellipta?
fluticasone furoate
vilanterol
emclidinium
What is in Breo Ellipta?
fluticasone furoate
vilanterol
What is in Incruse Ellipta?
umeclidinium
When is long-term oxygen therapy considered for COPD patients?
if either of the following criteria are documented twice in a 3 week period:
-PaO2 <55mmHG or SaO2 </=88% w/wo hypercapnia
-PaO2 55-60mmHg or SaO2 of 88% with evidence of right-sided heart failure, polycythemia, or pulmonary hypertension
When is noninvasive positive pressure ventilation (NPPV) used?
COPD with obstructive sleep apnea
What treatment should group E COPD patients receive?
LABA and LAMA
+ICS if eosinophils at least 300
+SABA pro
What treatment should group A COPD patients receive?
a bronchodilator
+SABA pro
What treatment should group B COPD patients receive?
LABA+LAMA
+SABA pro
In a patient on a LAMA or LABA presenting with dyspnea, what treatment should they receive?
LABA or LAMA
In a patient on a LABA with blood eos <300 experiencing an exacerbation, what treatment should they receive?
LABA+LAMA
In a patient on a LABA with blood eos >300 experiencing an exacerbation, what treatment should they receive?
LABA+LAMA+ICS
In a patient on LABA+LAMA with blood eos >100 experiencing an exacerbation, what treatment should they receive?
LABA+LAMA+ICS
In a patient on LABA+LAMA with blood eos <100 experiencing an exacerbation, what treatment should they receive?
Roflumilast or azithromycin
Ina patient on LABA+LAMA+ICS experiencing an exacerbation, what treatment should they receive?
Rolflumilast or azithromycin
What are possible etiologies of COPD exacerbations?
respiratory tract infections
peaks of air pollution
How is a COPD exacerbation diagnosed?
patient complaining of a acute change of symptoms (dyspnea, couch, and/or sputum production)
How are COPD exacerbations treated?
bronchodilators (SABA)
oral corticosteroids
antibiotics?
What is the dose of oral corticosteroids for a patients experiencing a cOPD exacerbation?
Prednisone 40mg PO QD 5D
What are tests run to diagnose COPD exacerbations?
pulse oximetry, ABG, chest x-ray, ECG, CBC, presence of purulent sputum, biochemical tests
When do the guidelines recommend antibiotic use in COPD exacerbations?
presence of three cardinal symptoms (dyspnea, sputum volume, sputum purulence)
presence of two of the carinal symptoms (one must be increase in sputum purulence)
require mechanical ventilation
How long should a patient receive antibiotics after a COPD exacerbation?
5-7 days
21-42 days of P. aeruginosa or MRSA
What antibiotics are used in uncomplicated COPD exacerbations?
macrolide
2nd or 3rd gen cephalosporin
doxycycline
What antibiotics are used in complicated COPD exacerbations?
augmentin
levofloxacin, gemifloxacin, moxifloxacin
What antibiotics are used in complicated COPD exacerbations with risk of P. aeruginosa?
levofloxacin
IV 3rd or 4th gen cephalosporin
What is considered an uncomplicated COPD exacerbation?
<4 exacerbations/year
no comorbid illness
FEV1 >50% of predicted
What is considered a complicated COPD exacerbation?
Age of at least 65 and >4 exacerbation/year
FEV1 35-50% of predicted
What is considered complicated COPD exacerbation with risk of P. aeruginosa?
chronic bronchial sepsis
need for chronic corticosteroid therapy
resident of nursing home with <4 exacerbations/year
FEV1 <35% of predicted
What is the target oxygen saturation for a patient with COPD?
88-92%
When is assisted ventilation indicated for a patient with COPD?
respiratory acidosis
severe dyspnea with clinical signs suggestive of respiratory muscle fatigue such as use of accessory muscles and paradoxical motion
What is the radiologic findings of interstitial lung disease?
diffuse interstitial markings
What is the clinical presentation of interstitial lung disease?
shortness of breath
dyspnea on exertion
What are risk factors for interstitial lung disease?
age
female gene
smoking
family history
occupation
infections
What are causes of acute interstitial lung disease?
HF exacerbation
infections
drugs
What are types of interstitial abnormality?
edema
diffuse inflammation
fibrosis
non-specific histologic changes
What are causes of fluid overload interstitial lung disease?
HF - specifically left ventricular systolic dysfunction
renal failure
nephrotic syndrome
ascites/anasarca
capillary leak
redistribution pulmonary edema
iatrogenic
What is the treatment for fluid overload interstitial lung disease?
treat underlying cause
fluid management
diuretics
What is the steroid treatment for pneumocystis jervoeci pneumonia?
Prednisone 40mg BID 5D then titrate down
What are causes of auto-immune interstitial lung disease?
RA
SLE
sarcoidosis
scleroderma
vasculitis
dermatomyositis
MCTD
overlap syndrome
What is the treatment for auto-immune interstitial lung disease?
treat the underlying cause
What are causes of industrial/environmental interstitial lung disease?
Asbestosis
berylliosis
silicosis (black lung)
hypersensitivity pneumonitis (black mold)
pollutants
What is the treatment of industrial/environmental interstitial lung disease?
prevention
oxygen therapy
steroids
When may neoplastic interstitial lung disease occur?
leukemia
lymphoma
metastatic cancer
What drugs may cause interstitial lungs disease?
amiodarone
bleomycin
At what doses does amiodarone cause pulmonary fibrosis?
long term doses >400mg per day
What is the most common type of idiopathic interstitial pneumonias?
idiopathic pulmonary fibrosis
What are risk factors for idiopathic pulmonary fibrosis?
smoking
occupational exposures
exposure to certain viruses
genetic predisposition?
What is the pathophysiology of idiopathic pulmonary fibrosis?
alveolar epithelial injury leading to fibrotic changes
What is the clinical presentation of idiopathic pulmonary fibrosis?
SOB and DOE
dry cough
fatigue and weight loss
finger clubbing
How is idiopathic pulmonary fibrosis diagnosed?
diagnosis of exclusion
What medications are used to treat idiopathic pulmonary fibrosis?
pirfenidone
nintedanib
Pirfenidone is a __ substrate
CYP1A2
Nintedanib is a __ substrate
CYP3A4
With CYP1A2 inhibitors, pirfenidone should __
be monitored and adjusted as needed
With CYP1A2 inducers, pirfenidone should __
be avoided
With Pgp and CYP3A4 inhibitors, nintedanib should _
be monitored and adjusted as needed
With Pgp and CYP inducers, nintedanib should __
be avoided
What are side effects of pirfenidone?
nausea, rash, fatigue, dispepsia, photosensitivity, anorexia, increased AST and ALT
In what patients is pirfenidone not recommended in?
patients with moderate-to-severe hepatic impairment
In what patients should pirfenidone be used with caution in?
patients with mild hepatic impairment
What are side effects of nintedanib?
diarrhea, nausea, and vomiting
small increase in risk of bleeding
What should be monitored regularly in use of pirfenidone and nintedanib?
LFTs
In what patients should nintedanib be used with caution in?
patients with CV disease or CV risk factors
In what patients is nintedanib not recommended in?
patients with moderate-to-severe hepatic impairment
What is the recommendation for nintedanib and patients with mild hepatic impairment?
decreased dose to 100mg BID
What is non-pharmacologic therapy for idiopathic pulmonary fibrosis?
flu, covid, and Prevnar vaccines
nutrition
exercise
smoking cessation
support groups
early referral for lung transplant
What is the mechanism of action of nintedanib?
inhibitor of the intracellular domain of tyrosine kinase receptors VEGF, FGF, and PDGF
decreases accumulation of fibrotic tissue
What is the mechanism of action of pirfenidone?
reduces collagen type I expression decreasing fibrosis
downregulagtes production of growth factors
What are examples of CYP1A2 inhibitors?
cimetidine
ciprofloxacin
fluvoxamine
What are examples of CYP1A2 inducers?
Omeprazole
smoking
What are SABAs?
Albuterol
Levalbuterol
What are LABAs?
Formoterol
Salmeterol
What are Ultra LABAs?
Indacaterol
Arformoterol
Olodaterol
Vilanterol
Which beta-adrenergic agonists don’t have substrates for COMT/MAO?
albuterol/levalbuteral
SABAs
What is the mechanism of action of beta adrenergic agonists?
smooth muscle relaxation by activating beta2 receptors and phosphorylation of proteins in smooth muscle
What are common ADEs of SABAs?
muscle tremor
CNS excitement
What are serious ADEs of SABAs?
tachycardia, hypokalemia
What is an ADE of LABAs?
severe asthma exacerbation and asthma-related death when used as monotherapy
What are ADEs of Indacaterol?
cough, headache
What is an ADE of Olodanterol?
Nasopharyngitis
What are drug interactions with SABAs?
nonselective beta blockers
diuretics
What are drug interactions with LABAs?
nonselective beta blockers
cannabinoids
haloperidol
MAOI and TCA
loop and thiazide diuretics
What are SAMAs?
ipratropium
What are LAMAs?
tiotrpoium
aclidinium
umeclidinium
glycopyrrolate
What is the mechanism of action of muscarinic antagonists?
block acetylcholine from binding m3 receptors
What are side effects of muscarinic antagonists?
xerostemia,
blurred vision
urinary retention
headache
diarrhea, vomiting
nasopharyngitis, cough, rhinos, sinusitis
tachycardia
Tiotropium may worsen the symptoms of __angle glaucoma
narrow
Ipratropium may cause paradoxical bronchospasm because of binding to the m__ receptor
2
What are inhaled corticosteroids?
beclomethasone
budesonide
ciclesonide
fluticasone
mometasone
What are systemic corticosteroids?
prednisone
prednisolone
methylprednisolone
Which corticosteroids are prodrugs?
beclomethasone
prednisone
ciclesidone
What corticosteroids have some mineralcorticoid activity?
prednisone
prednisolone
mometasone
What is the mechanism of action of corticosteroids?
binds to CBG
stimulates or inhibits gene transcription
inc anti inflammatory genes
dec inflammatory genes
What are side effects of inhaled corticosteroids?
headache
paharyngitis
oral candidiasis
cough
dyspnea
systemic side effects with high doses
What are side effects of systemic corticosteroids?
GI upset
hyperglycemia
psych disturbances
What drugs can interact with inhaled corticosteroids?
azoles
macrolides
CYP3A4 inducers and inhibitors
What drugs can interact with systemic corticosteroids?
antacids
fluoroquinolones
CYP3A4 inhibitors and inducers
phenytoin
warfarin
What is the mechanism of action of omalizumab?
IgG monoclonal antibody that binds to IgE
decrease the release of mediators from cellsdecrease allergic inflammation
What is the mechanism of action of dupilumab?
inhibits IL4 and IL13 cytokine-induced responses
What is the mechanism of action of mepolizumab and reslizumab?
binds to IL5
What is the mechanism of action of benralizumab?
binds to and blocks IL5 receptor
What is the mechanism of action of tezepelumab?
binds to TSLP and prevents its interaction with TSLP receptor complex
inhibits inflammatory pathways
What are the side effects of monoclonal antibodies?
anaphylaxis, headache, injection site reaction, antibody development
What are leukotriene modifiers?
montilukast
zafirlukast
What are side effects of montelukast?
dizziness, stomach pain, dyspepsia, headache, diarrhea, constipation, serious neuropsychiatric events
What is the mechanism of action of leukotriene modifiers?
block the action of leukotrienes by binding to the LT1 receptors in smooth muscle cells
What drugs interact with montelukast?
CYP2C9, 2C8, and 3A4/5 inhibitors and inducers
What drugs interact with zafirlukast?
phenytoin
CYP2C9 substrates
food decreases bioavailability
What are the classifications of pleural disease?
pleurisy
hemothorax, pneumothorax, chylothorax
pleural effusion
What is the definition of a tension pneumothorax?
acute rapidly expanding pneumothorax
pressure exerted on the heart and greater vessels cause hemodynamic instability
What is the clinical presentation of a hemothorax/pneumothorax/chylothorax?
SOB
DPE
chest pain and dyspnea
tachypnea
cough
What medications should be given when a chest tube thoracostomy is performed?
morphine
1st gen cephalosporin (cefazoline)
What is the definition of a pleural effusion?
fluid accumulation due to loss of fluid homeostasis
What is the fluid composition of a transduative pleural effusion?
just fluid
What is the fluid composition of exudative pleural effusion?
high protein
high cell count
high LDH
Which type of pleural effusion involves the pleural membrane?
exudative
What is the most common etiology of a transudative pleural effusion?
heart failure
What is the most common etiology of exudative pleural effusion?
pneumonia
What is the clinical presentation of pleural effusion?
SOB, DOE
cough
chest pain
tachypnea
may be asymptomatic
Of patients with pleural effusion, who gets treatment?
symptomatic and/or recurrent
What are intrapleural medication options for treatment of located effusions?
streptokinase
alteplase
dornase alfa
What is the purpose of chemical pleurodesis?
induce scarring
What agents are used for pleurodesis?
doxycycline
talc
bleomycin
What is the common presentation of drug-induced pulmonary disease?
apnea
asthma
bronchospasm
pulmonary edema
pulmonary eosinophilia
pulmonary fibrosis
What are risk factors for drug-induced pulmonary disease?
age
pre-existing lung disease
combination therapy
cumulative doses
oxygen therapy
radiation therapy
occupational risk factors
What medications may induce bronchospasm?
aspirin
beta-blockers
sulfites and other preservatives
contrast media
ACE inhibitors
N-acetylcystiene
natural rubber latex allergies
What is the most common drug-induced pulmonary disease?
bronchospasm
What are risk factors for apnea/respiratory depression?
age
COPD (pre-existing pulmonary disease)
CO2 retention
dose
multiple agents
What are symptoms of pulmonary eosinophilia?
fever
productive cough
dyspnea
cyanosis
bilateral pulmonary infiltrates
eosinophilia in the blood
What drugs can cause pulmonary hypertension?
cocaine
oral contraceptives
amphetamines
chemotherapeutic agents
anorexic agents
What are symptoms of aspirin-induced bronchospasm?
intense vasomotor rhinitis
bronchospams
flushing of head and neck
conjunctivitis
What is the treatment for N-actylcystiene-induced pulmonary disease?
administer beta2 agonist with or immediately prior to N-acetylcystiene
What drugs can cause pulmonary eosinophilia?
nitrofurantoin
para-aminosalicylic acid
methotrexate
sulfonamides
tetracycline
chlorpropamide
phenytoin
NSAIDs
imipramine
What are signs and symptoms of drug-induced pulmonary fibrosis?
dyspnea
hypoxemia
nonproductive cough
diffuse alveolar damage
interstitial pneumonitis
What are etiologies of asthma?
genetic factors
environmental factors
obesity
What are the stages of airway obstruction?
airway smooth muscle constriction
airway edema
mucus hypersecretion
airway remodeling
What are symptoms of asthma?
varies over time and intensity
wheezing, SOB, chest tightness, coughing
anxious and agitated
mental status changes may indicate respiratory failure
What are signs of asthma?
tachypnea
tachycardia
use of accessory muscles
auscultation: end expiratory wheezing or wheezing trough inspiration and expiration
What are laboratory test performed for asthma?
spirometry <80% after receiving bronchodilator
Increased IgE
RAST
FeNO
What is considered Mild acute asthma?
dyspnea with activity
>/=70% PEF of personal best
What is considered moderate acute asthma?
dyspnea that limits activity
40-69% PEF of personal best
What is considered severe acute asthma?
dyspnea interferes with conversation or occurs at rest
25-40% PEF of personal best
What is considered life-threatening acute asthma?
dyspnea where the patient can’t speak
<25% PEF of personal best
What is nonpharmacologic therapy for asthma?
smoking cessation
5-10% weight loss in obese
avoid triggers
vaccination
What is considered medium-dose fluticasone for children?
> 200-500
What is considered medium-dose fluticasone for adults?
> 250-500
What decreases response to inhaled corticosteroids?
cigarette smoking
What is the duration for systemic corticosteroids in acute asthma?
3-10 days
When is a SAMA indicated in asthma?
in the emergency department
Leukotriene modifiers are beneficial in which patients?
allergic rhinitis
aspirin sensitivity
What is is the preferred treatment for a patient with asthma attacks less than twice a month? What step are they?
Step 1
as-needed low-dose ICS-formoterol
What is the preferred treatment for a patient with asthma symptoms twice a month or more? what step are they?
Step 2
as-needed low-dose ICS-formoterol
What is the preferred treatment for a patient with asthma symptoms 4-5 days/week or waking once a week or more? What step are they?
Step 3
Low-dose ICS-formoterol and reliever therapy
What is the preferred treatment for a patient with severely uncontrolled asthma initially or an acute exacerbation? What step are they?
Step 4
Medium-dose ICS-formoterol and reliever therapy
When should a patient follow up after initial therapy of asthma treatment?
2-3 months
What is considered mild chronic asthma?
well controlled with step 1 or 2 treatment
What is considered moderate chronic asthma?
well controlled with step 3 or 4 treatment
What is considered severe chronic asthma?
remains uncontrolled despite optimized treatment
What are the four questions asked to assess asthma symptom control?
Daytime asthma symptoms more than twice/week?
Any night waking due to asthma?
SABA reliever for symptoms more than twice/week?
Any activity limitation due to asthma?
If 1-2 of the symptom control asthma questions are yes, what is the step?
step up one
If 3-4 of the symptom control asthma questions are yes, what is the step?
step up two
When is a step down in therapy considered for a patient with asthma?
3 months controlled
What is the target oxygen saturation for children, pregnant women, and patients with coexisting heart disease? All other patients?
94-98%
93-95%
what is the core pharmacophore of beta2 adrenergic agonists?
substituted beta-phenyl ethylamine
What are two key modifications of endogenous catecholamines achieving selectivity for beta2 adrenergic receptors?
Suitable substituents other than hydroxyls at phenyl ring
Ethyl substituent at alpha carbon
How many carbons need to be attached to the catecholamine nitrogen to achieve a) selectivity for beta over alpha receptors b) selectivity for beta2 receptors?
> 1
3
List four ways by which the duration of action of adrenergic agonists can be increased.
Increase affinity for the receptor
Binding to exosites of the receptor
Increase lipophilicity of inhaled drugs
Substitutions that mask sites recognized by metabolizing enzymes
Resistance to two enzymes prolong the duration of action of adrenergic agonists. What are they?
COMT and MAO
Which modifications generate resistance to metabolic inactivation of adrenergic agonists?
In the hydrophobic pocket on the positive nitrogen
On the alpha carbon
On the phenyl ring
List two ways by which the retention of beta2-adrenergic agonists in the lungs can be achieved (consider Lipinski’s rule of 5).
High lipophilicity
High hydrophilicity
Why has formoterol a faster onset of action than salmeterol?
Greater water solubility
What is the difference between formoterol and arformoterol?
Arformoterol is the r,r enantoimer
What is the main reason why olodaterol has a long duration of action in lungs?
Fast and high affinity association with receptor and slow dissociation
What is the key structural modification that converts acetylcholine into an antagonist? Which structure in the receptor ligand binding site does this modification interact with (name the transmembrane helices that form that structure)?
Methyl group replaced with system containing at least one phenyl or dithienyl ring
VII
What is a common structural feature of all anti-muscarinic drugs?
Positive quaternary amine
Why are ipratropium and tiotropium poorly absorbed from the lungs and why do they have no oral availability? (consider charge, hydrophobicity, affinity)?
Highly hydrophilic, quaternary ammonium nitrogen
Name two drugs that inhibit phosphodiesterase-4 (PDE4), one selectively and one non-selectively. You should recognize their structures and know what treatment modality they are used for.
Roflumilast - selective
Theophylline - nonselective
Why is prednisone a prodrug?
the carbonyl must be converted to hydroxy in vivo
Why has prednisolone more anti-inflammatory activity than hydrocortisone and a longer duration of action (a single change from hydrocortisone)?
The double bind at the C1-2 position
Which of all topical glucocorticoid drugs has the highest affinity for the glucocorticoid receptor?
mometasone
Explain the components of the name “omalizumab” in terms of the international Nonproprietary Names Program of the WHO. What is the meaning of LI and ZU?
LI: immunomodulating
ZU: humanized
What is the main reason for the effectiveness of anti-IL-5 and antiI-IL-5R antibodies? The activation of which cell type is inhibited? Which subtype of asthma is treated with these antibodies?
Activation of eosinophils
Eosinophilic asthma
What is the target of Dupilumab? What the chemical nature of this drug? To what degree it is humanized?
IL4 and IL13
Reduces typeII inflammation and asthma exacerbation
Fully human
What is TSLP? What role is it playing in the pathogenesis of asthma? Name a biotechnology product that blocks this molecule.
Thymic stromal lymphopoietin is an alarmin released by epithelial or stromal cells
Airway inflammation and hyperresponsiveness
Tezepalumab
Which type of mechanism underlying drug-induced pulmonary disorders (intolerance) would you expect to be specific to a particular drug molecule and which type of mechanism would lead to intolerance to an entire class of drugs?
Aspirin
Which atomic element that occurs in commonly used contrast media is responsible for their high X-ray density?
iodine
Which type of contrast agents have a high rate of adverse effects, which have a lower rate? What is the critical difference?
High osmolar, ionic
Low osmolar, nonionic
Talc is what type of mineral?
silicate
Why are toxic molecules like bleomycin and talk useful in the treatment of pleural disease? What effect do they have that is beneficial?
induce scarring
When injected by intravenous drug users, talc elicits which type of response in the lung?
foreign body response
What is the mechanism of toxicity common to doxycycline, other tetracyclines, and bleomycin? What other element is involved?
chelates ions
iron
What is the target protein of Nintedanib (Nintedanib blocks which type of receptor)? What is the binding site?
Tyrosine-kinase type receptors
ATP site of FGFR
What is the biological effect of pirfenidone?
decreases fibrosis
What type of reactions occur during the metabolism of Pirfenidone?
Benzylic hydroxylation by CYP1A2
Cystolic oxidation to carboxylic acid
How is pirfenidone eliminated?
urine
What is the target of dornase alfa?
DNA
What is the content of Pancrelipase microsphere used for the treatment of cystic fibrosis?
Digestive enzymes and bicarbonate buffer
How is CFTR activated, how is it gated?
Activated by PKA
Gated by ATP
What is the effect of CRTR correctors versus that potentiators?
Corrects misfolding, prevents degradation of CFTR proteins
Which common mutation can be “rescued” with CFTR correctors?
F508del
Which of the following cystic fibrosis drugs is/are a potentiator which is a corrector? Ivacaftor, lumacaftor, tezacaftor, elexacaftor?
Potentiator: Ivacaftor
Corrector: Lumacaftor, Tezecaftor, Elexacaftor
What is a common structural feature of all cystic fibrosis drugs (answer in lecture recording, not in slides)?
the cyclic ring
Name main metabolizing enzymes of the cytochrome P450 superfamily that metabolize ivacaftor, lumacaftor, and elexacaftor?
CYP3A4/5
