Pulmonary Flashcards
(336 cards)
1
Q
What is the definition of cystic fibrosis?
A
dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR)
2
Q
What is the most common life-limiting genetic disorder in caucasians?
A
Cystic fibrosis
3
Q
What organ systems are affected by cystic fibrosis?
A
lungs
digestive system
reproductive system
4
Q
What is the most common mutation in the CFTR gene?
A
F508del
5
Q
Cystic fibrosis is an autosomal __ disease
A
recessive
6
Q
__ occurs in the distal airways of the lung and submucosal glands that express CFTR
A
Mucosal obstruction
7
Q
CFTR regulates __ across the cell membrane
A
chloride transport
8
Q
CFTR helps regulate ion transport and __ homeostasis
A
salt
9
Q
What is the effect go a CF gene defect in the lungs?
A
decreased airway surface liquid
colliery collapse and decreased mucocilliary transport
10
Q
CF in the lungs is a vicious cycle of mucus retention, infection, and __
A
inflammation
11
Q
What class of mutation is categorized by no traffic?
A
Class II
12
Q
What is the presentation of CF in the sinus and pulmonary systems?
A
chronic infections and nasal polyps
SOB and cough with sputum production daily
flat diaphragm
decreased FEV1
digital clubbing from chronic hypoxia
13
Q
What is the presentation of CF in the GI system?
A
pancreatic insufficiency
meconium ileum, steatorrhea, and failure to thrive due to malabsorption
older patients: severe constipation and insulin deficiency
14
Q
What is the presentation of CF in the male reproductive system?
A
Azoospermia
15
Q
What is the presentation of CF in the female reproductive system?
A
Decreased fertility
16
Q
T or F: all states require CF newborn screening
A
True
17
Q
What two tests are used to diagnose CF?
A
Immunoreactive trypsinogen (IRT) screening test
Quantitative pilocarpine iontophoresis sweat test (QPIT) (or sweat chloride test)
18
Q
What is a diagnostic level of chloride content when using the QPIT?
A
> 60 mmol/L
19
Q
What is nonpharmacologic therapy for CF?
A
Adults: normal weight
Pediatrics: normal growth
Require 110-200% energy take
20
Q
What medication is used to treat nutrient malabsorption due to pancreatic insufficiency?
A
Pancrelipase
21
Q
What is a typical dose for pancrelipase?
A
500-2500 lipase units/kg/meal
22
Q
What can happen if the patient takes too much pancrelipase?
A
Colonic strictures
23
Q
What are risk factors for pancrelipase-induced colonic strictures?
A
<12 years old
>6000 lipas units/kg/meal for >6 months
history of meconium ileus
history of intestinal surgery
IBS
24
Q
When should colonic stricture be considered?
A
evidence of obstruction
bloody diarrhea
abdominal pain
poor weight gain
25
What formulations does pancrelipase come in?
Capsules with enteric coated microspheres
Enteric coated tablets
26
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
27
What vitamins are fat soluble?
A, D, E, K
28
What is a goal vitamin D level?
>/=30 ng/mL
29
What test should be obtained for all adults that is related to bone health and vitamin supplementation?
Dual x-ray absorptiometry (DXA)
30
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
31
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
32
In a CF patient, what is the protocol is the T/Z score is
Consider bisphosphonate
Repeat annually
33
When should airway clearance therapy be initiated in a CF patient?
within the first few months of life
34
What are the different examples of chest percussion?
Cupped hand pounding
Percussion vest
Aerobic exercise
35
What is the order of clearance therapy for patients with CF receiving chest percussion?
Bronchodilator
Hypertonic saline
Dornase alfa
Aerosolized antibiotic
36
What are examples of aerosolized antibiotics?
aztreonam
tobramycin
37
What are examples of anti-inflammatory drugs used in CF patients?
high-dose ibuprofen (20-30 mg/kg BID)
azithromycin
38
What bacteria is found in the early stages of CF?
staphylococcus aureus
39
What bacteria is found in the later stages of CF?
pseudomonas aeruginosa
40
What is the treatment of stenotrophomonas in CF patients?
Bactrim or doxycyline
41
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
42
What vaccinations should CF patients get?
annual flu vaccine
Pneumonia
Covid
43
When does CF related diabetes usually present?
18-21 years
44
What is the therapy of choice in patients with CF related diabetes?
insulin
45
What is the indication for Ivacaftor (Kalydeco)?
Class III mutation
at least 1 month
46
What is the indication for Lumacaftor/Ivacaftor (Orkambi)?
Homozygous F508del
at least 1 year
47
What is the indication for Tezacaftor/Ivacaftor (Symdeko)?
Homozygous F508del
at least 6 years
48
What is the indication for Elexacafotr/Tezecaftor/Ivacaftor (Trikafta)?
at least one F508del mutation
at least 2 years
49
Increased oxygen uptake, blood volume, and cardiac output in pregnancy of a CF patient may lead to what complication?
right-sided heart failure
50
CF candidates for transplant are those with a FEV1 < __
30%
51
When should CF patients follow up with their provider?
every 1-3 months
52
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
53
What CF medication is a potentiator?
Ivacaftor
54
What CF medications are correctors?
Lumacaftor
Tezacaftor
Elexacaftor
55
Most CF medications have ___ absorption with fatty food
increased
56
The Cf medications are metabolized by __
CYP3A4/5
57
CFTR is a __-activated anion (CL-) channel
cAMP
58
What is the mechanism of action of Ivacaftor?
It binds to the defective protein at the cell surface and opens the chloride channel
59
What is the mechanism of action of Lumacaftor?
It corrects the processing and trafficking of defected CFTR protein
60
What are side effects of CFTR modulators?
headache, dizziness, skin rash, abdominal pain, diarrhea, nausea, nasal congestion, oropharyngeal pain, upper respiratory tract infection, nasopharyngitis
61
What are DDIs with CFTR modulators?
CYP3A4 inhibitors (Cimetidine, fluconazole, ketoconazole, grapefruit juice)
62
How is dornase alfa administered?
inhalation
63
What is the source of dornase alfa?
recombinant human DNase I
64
What are side effects of dornase alfa?
chest paine, voice disorder, cough, pharyngitis, rhinitis, skin rash, dyspnea
65
What is the mechanism of action of dornase alfa?
hydrolyzes the DNA of mucus in CF patients to decrease mucus viscosity
66
What is the source of pancrelipase?
contains a combination of lipase, amylase, and proteases
natural product from porcine pancreatic glands
67
What are side effects of pancrelipase?
headache, neck pain, abdominal pain, nasal congestion
68
What are examples of methylxanthines?
theophylline
caffeine
69
Theophylline has a __ therapeutic index
narrow
70
T or F: Theophylline has significant first pass metabolism
False
71
What enzyme metabolizes theophylline?
CYP1A2
72
A high fat meal __ absorption of theophylline
decreases
73
Increased cAMP causes __
bronchodilation
74
Increased cGMP causes __
decreased inflammatory cells
75
Theophylline is a __ PDE inhibitor
non-selective
76
Theophylline block the __ receptor and causes increased heart rate and vasoconstriction
adenosine
77
What medications decrease clearance of theophylline?
Cimetidine, macrolides, allopurinol, propranolol, quinolones
78
What medications increase clearance of theophylline?
Carbamazepine, phenytoin, moricizine
79
Smokers have __ clearance
increased
80
What are side effects of theophylline at lower concentrations?
headache, nausea, vomiting, insomnia
81
What are side effects of theophylline at higher concentrations?
arrhythmias, seizures, death
82
The side effects of theophylline at higher concentrations are due to __ effects.
adenosine
83
Roflumilast is metabolized by __ and __
CYP 3A4 and 1A2
84
Roflimulast is a __ PDE inhibitor
selective
85
What is the mechanism of action of roflimulast?
inhibition of PDE4
increases cAMP levels
Decrease inflammatory cells and cytokines, decrease bronchoconstriction, decrease vascular permeability
86
What are side effects of rolflimulast?
headache, insomnia, anxiety, depression, decreased appetite, weight loss, nausea, diarrhea, abdominal pain
87
Does roflumilast antagonize the adenosine system?
no
88
What medications decrease roflumilast concentrations?
CYP3A4 inducers (rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, St John's wort)
89
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
90
What is the definition of emphysema?
Destruction of alveoli
No obvious fibrosis
91
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
92
What are the three components of the mechanistic triad of COPD?
inflammation
imbalance between proteases and antiproteases
oxidative stress
93
In the central airways, inflammatory cells and mediators stimulate __
mucus-secreting gland hyperplasia
mucus hypersecretion
94
What is the major site of airflow obstruction in COPD?
peripheral airways
95
Advance COPD can lead to __
hypoxemia
hypercapnia
96
What is hypercapnia
abnormally elevated carbon dioxide levels in the blood
97
Pulmonary hypertension in a COPD patient can lead to __
cor pulmonale (right-sided heart failure)
98
COPD patients can get progressive loss of __ muscle
skeletal
99
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
100
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
101
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
102
Post bronchodilator FEV1/FVC < __ confirms presence of persistent airflow limitation
70%
103
What is a GOLD1 classification?
mild
FEV >/=80& predicted
104
What is GOLD2 classification?
moderate
FEV1 50-80% predicted
105
What is GOLD3 classification?
severe
FEV1 30-50% predicted
106
What is GOLD4 classification?
very severe
FEV1 <30% predicted
107
What two tests are sued to assess symptoms in COPD patients?
mMRC
CAT
108
How is a COPD patient classified as E?
>/=2 moderate exacerbations or >/=1 leading to hospitalization
109
How is a COPD patient classified as A?
0 or 1 moderate exacerbations not leading to hospitalization
AND CAT <10
110
How is a COPD patients classified as B?
0 or 1 moderated exacerbations not leading ti hospitalization
AND CAT >/= 10
111
What are the desired outcomes of treating a COPD patient?
reduce symptoms
reduce risk
smoking cessation
112
What is the green zone for a COPD patient?
usual activity level
usual amount of phlegm/mucus
take daily medications
113
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
114
What is the red zone for a COPD patient?
severe SOB, even at rest
coughing up blood
call 911 or seek immediate medical care
115
What is the only intervention to slow disease progression and long-term FEV1 decline?
smoking cessation
116
What immunizations should COPD patients get?
annual flu vaccine
pneumonia vaccine
Tdap
Covid
117
What are the components of pulmonary rehabilitation?
exercise training
breathing techniques
education
psychological and nutritional counseling
118
Optimum benefit is achieved with a pulmonary rehabilitation program lasting __
6-8 weeks
119
When should COPD patients do pulmonary rehabilitation?
at diagnosis
hospital discharge following an exacerbation
progressively deteriorating symptoms
120
What is the mainstay of treatment for symptomatic COPD?
bronchodilators
121
What are SABA key points in COPD?
rescue therapy for acute relief
avoid continuous, daily therapy
122
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
123
What are examples of combination bronchodilator products?
albuterol/ipratropium (Combivent)
Vilanterol/umeclidinium (Anoro)
124
What is the indication for theophylline?
patients who cannot use inhaled medications or are symptomatic despite appropriate use of inhaled bronchodilators
125
What is the target concentration for theophylline in COPD patients?
5-15 mg/L
126
What conditions increase concentrations of theophylline?
heart failure
liver disease
127
What conditions decrease concentrations of theophylline?
high protein diet
128
Theophylline should be dosed based on __
IBW
129
When converting from aminophylline to theophylline you __
multiply by 0.8
130
When converting from theophylline to aminophylline you __
divide by 0.8
131
Theophylline has __ kinetics
non-linear
132
What are key points for corticosteroids in COPD?
monotherapy is not recommended
avoid long-term use of oral corticosteroids
133
When is rolflumilast indicated?
severe or very severe COPD and a history of exacerbations
134
What is the onset for rolflumilast?
4 weeks
135
What is in Trelegy Ellipta?
fluticasone furoate
vilanterol
emclidinium
136
What is in Breo Ellipta?
fluticasone furoate
vilanterol
137
What is in Incruse Ellipta?
umeclidinium
138
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
139
When is noninvasive positive pressure ventilation (NPPV) used?
COPD with obstructive sleep apnea
140
What treatment should group E COPD patients receive?
LABA and LAMA
+ICS if eosinophils at least 300
+SABA pro
141
What treatment should group A COPD patients receive?
a bronchodilator
+SABA pro
142
What treatment should group B COPD patients receive?
LABA+LAMA
+SABA pro
143
In a patient on a LAMA or LABA presenting with dyspnea, what treatment should they receive?
LABA or LAMA
144
In a patient on a LABA with blood eos <300 experiencing an exacerbation, what treatment should they receive?
LABA+LAMA
145
In a patient on a LABA with blood eos >300 experiencing an exacerbation, what treatment should they receive?
LABA+LAMA+ICS
146
In a patient on LABA+LAMA with blood eos >100 experiencing an exacerbation, what treatment should they receive?
LABA+LAMA+ICS
147
In a patient on LABA+LAMA with blood eos <100 experiencing an exacerbation, what treatment should they receive?
Roflumilast or azithromycin
148
Ina patient on LABA+LAMA+ICS experiencing an exacerbation, what treatment should they receive?
Rolflumilast or azithromycin
149
What are possible etiologies of COPD exacerbations?
respiratory tract infections
peaks of air pollution
150
How is a COPD exacerbation diagnosed?
patient complaining of a acute change of symptoms (dyspnea, couch, and/or sputum production)
151
How are COPD exacerbations treated?
bronchodilators (SABA)
oral corticosteroids
antibiotics?
152
What is the dose of oral corticosteroids for a patients experiencing a cOPD exacerbation?
Prednisone 40mg PO QD 5D
153
What are tests run to diagnose COPD exacerbations?
pulse oximetry, ABG, chest x-ray, ECG, CBC, presence of purulent sputum, biochemical tests
154
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
155
How long should a patient receive antibiotics after a COPD exacerbation?
5-7 days
21-42 days of P. aeruginosa or MRSA
156
What antibiotics are used in uncomplicated COPD exacerbations?
macrolide
2nd or 3rd gen cephalosporin
doxycycline
157
What antibiotics are used in complicated COPD exacerbations?
augmentin
levofloxacin, gemifloxacin, moxifloxacin
158
What antibiotics are used in complicated COPD exacerbations with risk of P. aeruginosa?
levofloxacin
IV 3rd or 4th gen cephalosporin
159
What is considered an uncomplicated COPD exacerbation?
<4 exacerbations/year
no comorbid illness
FEV1 >50% of predicted
160
What is considered a complicated COPD exacerbation?
Age of at least 65 and >4 exacerbation/year
FEV1 35-50% of predicted
161
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
162
What is the target oxygen saturation for a patient with COPD?
88-92%
163
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
164
What is the radiologic findings of interstitial lung disease?
diffuse interstitial markings
165
What is the clinical presentation of interstitial lung disease?
shortness of breath
dyspnea on exertion
166
What are risk factors for interstitial lung disease?
age
female gene
smoking
family history
occupation
infections
167
What are causes of acute interstitial lung disease?
HF exacerbation
infections
drugs
168
What are types of interstitial abnormality?
edema
diffuse inflammation
fibrosis
non-specific histologic changes
169
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
170
What is the treatment for fluid overload interstitial lung disease?
treat underlying cause
fluid management
diuretics
171
What is the steroid treatment for pneumocystis jervoeci pneumonia?
Prednisone 40mg BID 5D then titrate down
172
What are causes of auto-immune interstitial lung disease?
RA
SLE
sarcoidosis
scleroderma
vasculitis
dermatomyositis
MCTD
overlap syndrome
173
What is the treatment for auto-immune interstitial lung disease?
treat the underlying cause
174
What are causes of industrial/environmental interstitial lung disease?
Asbestosis
berylliosis
silicosis (black lung)
hypersensitivity pneumonitis (black mold)
pollutants
175
What is the treatment of industrial/environmental interstitial lung disease?
prevention
oxygen therapy
steroids
176
When may neoplastic interstitial lung disease occur?
leukemia
lymphoma
metastatic cancer
177
What drugs may cause interstitial lungs disease?
amiodarone
bleomycin
178
At what doses does amiodarone cause pulmonary fibrosis?
long term doses >400mg per day
179
What is the most common type of idiopathic interstitial pneumonias?
idiopathic pulmonary fibrosis
180
What are risk factors for idiopathic pulmonary fibrosis?
smoking
occupational exposures
exposure to certain viruses
genetic predisposition?
181
What is the pathophysiology of idiopathic pulmonary fibrosis?
alveolar epithelial injury leading to fibrotic changes
182
What is the clinical presentation of idiopathic pulmonary fibrosis?
SOB and DOE
dry cough
fatigue and weight loss
finger clubbing
183
How is idiopathic pulmonary fibrosis diagnosed?
diagnosis of exclusion
184
What medications are used to treat idiopathic pulmonary fibrosis?
pirfenidone
nintedanib
185
Pirfenidone is a __ substrate
CYP1A2
186
Nintedanib is a __ substrate
CYP3A4
187
With CYP1A2 inhibitors, pirfenidone should __
be monitored and adjusted as needed
188
With CYP1A2 inducers, pirfenidone should __
be avoided
189
With Pgp and CYP3A4 inhibitors, nintedanib should _
be monitored and adjusted as needed
190
With Pgp and CYP inducers, nintedanib should __
be avoided
191
What are side effects of pirfenidone?
nausea, rash, fatigue, dispepsia, photosensitivity, anorexia, increased AST and ALT
192
In what patients is pirfenidone not recommended in?
patients with moderate-to-severe hepatic impairment
193
In what patients should pirfenidone be used with caution in?
patients with mild hepatic impairment
194
What are side effects of nintedanib?
diarrhea, nausea, and vomiting
small increase in risk of bleeding
195
What should be monitored regularly in use of pirfenidone and nintedanib?
LFTs
196
In what patients should nintedanib be used with caution in?
patients with CV disease or CV risk factors
197
In what patients is nintedanib not recommended in?
patients with moderate-to-severe hepatic impairment
198
What is the recommendation for nintedanib and patients with mild hepatic impairment?
decreased dose to 100mg BID
199
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
200
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
201
What is the mechanism of action of pirfenidone?
reduces collagen type I expression decreasing fibrosis
downregulagtes production of growth factors
202
What are examples of CYP1A2 inhibitors?
cimetidine
ciprofloxacin
fluvoxamine
203
What are examples of CYP1A2 inducers?
Omeprazole
smoking
204
What are SABAs?
Albuterol
Levalbuterol
205
What are LABAs?
Formoterol
Salmeterol
206
What are Ultra LABAs?
Indacaterol
Arformoterol
Olodaterol
Vilanterol
207
Which beta-adrenergic agonists don't have substrates for COMT/MAO?
albuterol/levalbuteral
SABAs
208
What is the mechanism of action of beta adrenergic agonists?
smooth muscle relaxation by activating beta2 receptors and phosphorylation of proteins in smooth muscle
209
What are common ADEs of SABAs?
muscle tremor
CNS excitement
210
What are serious ADEs of SABAs?
tachycardia, hypokalemia
211
What is an ADE of LABAs?
severe asthma exacerbation and asthma-related death when used as monotherapy
212
What are ADEs of Indacaterol?
cough, headache
213
What is an ADE of Olodanterol?
Nasopharyngitis
214
What are drug interactions with SABAs?
nonselective beta blockers
diuretics
215
What are drug interactions with LABAs?
nonselective beta blockers
cannabinoids
haloperidol
MAOI and TCA
loop and thiazide diuretics
216
What are SAMAs?
ipratropium
217
What are LAMAs?
tiotrpoium
aclidinium
umeclidinium
glycopyrrolate
218
What is the mechanism of action of muscarinic antagonists?
block acetylcholine from binding m3 receptors
219
What are side effects of muscarinic antagonists?
xerostemia,
blurred vision
urinary retention
headache
diarrhea, vomiting
nasopharyngitis, cough, rhinos, sinusitis
tachycardia
220
Tiotropium may worsen the symptoms of __angle glaucoma
narrow
221
Ipratropium may cause paradoxical bronchospasm because of binding to the m__ receptor
2
222
What are inhaled corticosteroids?
beclomethasone
budesonide
ciclesonide
fluticasone
mometasone
223
What are systemic corticosteroids?
prednisone
prednisolone
methylprednisolone
224
Which corticosteroids are prodrugs?
beclomethasone
prednisone
ciclesidone
225
What corticosteroids have some mineralcorticoid activity?
prednisone
prednisolone
mometasone
226
What is the mechanism of action of corticosteroids?
binds to CBG
stimulates or inhibits gene transcription
inc anti inflammatory genes
dec inflammatory genes
227
What are side effects of inhaled corticosteroids?
headache
paharyngitis
oral candidiasis
cough
dyspnea
systemic side effects with high doses
228
What are side effects of systemic corticosteroids?
GI upset
hyperglycemia
psych disturbances
229
What drugs can interact with inhaled corticosteroids?
azoles
macrolides
CYP3A4 inducers and inhibitors
230
What drugs can interact with systemic corticosteroids?
antacids
fluoroquinolones
CYP3A4 inhibitors and inducers
phenytoin
warfarin
231
What is the mechanism of action of omalizumab?
IgG monoclonal antibody that binds to IgE
decrease the release of mediators from cellsdecrease allergic inflammation
232
What is the mechanism of action of dupilumab?
inhibits IL4 and IL13 cytokine-induced responses
233
What is the mechanism of action of mepolizumab and reslizumab?
binds to IL5
234
What is the mechanism of action of benralizumab?
binds to and blocks IL5 receptor
235
What is the mechanism of action of tezepelumab?
binds to TSLP and prevents its interaction with TSLP receptor complex
inhibits inflammatory pathways
236
What are the side effects of monoclonal antibodies?
anaphylaxis, headache, injection site reaction, antibody development
237
What are leukotriene modifiers?
montilukast
zafirlukast
238
What are side effects of montelukast?
dizziness, stomach pain, dyspepsia, headache, diarrhea, constipation, serious neuropsychiatric events
239
What is the mechanism of action of leukotriene modifiers?
block the action of leukotrienes by binding to the LT1 receptors in smooth muscle cells
240
What drugs interact with montelukast?
CYP2C9, 2C8, and 3A4/5 inhibitors and inducers
241
What drugs interact with zafirlukast?
phenytoin
CYP2C9 substrates
food decreases bioavailability
242
What are the classifications of pleural disease?
pleurisy
hemothorax, pneumothorax, chylothorax
pleural effusion
243
What is the definition of a tension pneumothorax?
acute rapidly expanding pneumothorax
pressure exerted on the heart and greater vessels cause hemodynamic instability
244
What is the clinical presentation of a hemothorax/pneumothorax/chylothorax?
SOB
DPE
chest pain and dyspnea
tachypnea
cough
245
What medications should be given when a chest tube thoracostomy is performed?
morphine
1st gen cephalosporin (cefazoline)
246
What is the definition of a pleural effusion?
fluid accumulation due to loss of fluid homeostasis
247
What is the fluid composition of a transduative pleural effusion?
just fluid
248
What is the fluid composition of exudative pleural effusion?
high protein
high cell count
high LDH
249
Which type of pleural effusion involves the pleural membrane?
exudative
250
What is the most common etiology of a transudative pleural effusion?
heart failure
251
What is the most common etiology of exudative pleural effusion?
pneumonia
252
What is the clinical presentation of pleural effusion?
SOB, DOE
cough
chest pain
tachypnea
may be asymptomatic
253
Of patients with pleural effusion, who gets treatment?
symptomatic and/or recurrent
254
What are intrapleural medication options for treatment of located effusions?
streptokinase
alteplase
dornase alfa
255
What is the purpose of chemical pleurodesis?
induce scarring
256
What agents are used for pleurodesis?
doxycycline
talc
bleomycin
257
What is the common presentation of drug-induced pulmonary disease?
apnea
asthma
bronchospasm
pulmonary edema
pulmonary eosinophilia
pulmonary fibrosis
258
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
259
What medications may induce bronchospasm?
aspirin
beta-blockers
sulfites and other preservatives
contrast media
ACE inhibitors
N-acetylcystiene
natural rubber latex allergies
260
What is the most common drug-induced pulmonary disease?
bronchospasm
261
What are risk factors for apnea/respiratory depression?
age
COPD (pre-existing pulmonary disease)
CO2 retention
dose
multiple agents
262
What are symptoms of pulmonary eosinophilia?
fever
productive cough
dyspnea
cyanosis
bilateral pulmonary infiltrates
eosinophilia in the blood
263
What drugs can cause pulmonary hypertension?
cocaine
oral contraceptives
amphetamines
chemotherapeutic agents
anorexic agents
264
What are symptoms of aspirin-induced bronchospasm?
intense vasomotor rhinitis
bronchospams
flushing of head and neck
conjunctivitis
265
What is the treatment for N-actylcystiene-induced pulmonary disease?
administer beta2 agonist with or immediately prior to N-acetylcystiene
266
What drugs can cause pulmonary eosinophilia?
nitrofurantoin
para-aminosalicylic acid
methotrexate
sulfonamides
tetracycline
chlorpropamide
phenytoin
NSAIDs
imipramine
267
What are signs and symptoms of drug-induced pulmonary fibrosis?
dyspnea
hypoxemia
nonproductive cough
diffuse alveolar damage
interstitial pneumonitis
268
What are etiologies of asthma?
genetic factors
environmental factors
obesity
269
What are the stages of airway obstruction?
airway smooth muscle constriction
airway edema
mucus hypersecretion
airway remodeling
270
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
271
What are signs of asthma?
tachypnea
tachycardia
use of accessory muscles
auscultation: end expiratory wheezing or wheezing trough inspiration and expiration
272
What are laboratory test performed for asthma?
spirometry <80% after receiving bronchodilator
Increased IgE
RAST
FeNO
273
What is considered Mild acute asthma?
dyspnea with activity
>/=70% PEF of personal best
274
What is considered moderate acute asthma?
dyspnea that limits activity
40-69% PEF of personal best
275
What is considered severe acute asthma?
dyspnea interferes with conversation or occurs at rest
25-40% PEF of personal best
276
What is considered life-threatening acute asthma?
dyspnea where the patient can't speak
<25% PEF of personal best
277
What is nonpharmacologic therapy for asthma?
smoking cessation
5-10% weight loss in obese
avoid triggers
vaccination
278
What is considered medium-dose fluticasone for children?
>200-500
279
What is considered medium-dose fluticasone for adults?
>250-500
280
What decreases response to inhaled corticosteroids?
cigarette smoking
281
What is the duration for systemic corticosteroids in acute asthma?
3-10 days
282
When is a SAMA indicated in asthma?
in the emergency department
283
Leukotriene modifiers are beneficial in which patients?
allergic rhinitis
aspirin sensitivity
284
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
285
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
286
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
287
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
288
When should a patient follow up after initial therapy of asthma treatment?
2-3 months
289
What is considered mild chronic asthma?
well controlled with step 1 or 2 treatment
290
What is considered moderate chronic asthma?
well controlled with step 3 or 4 treatment
291
What is considered severe chronic asthma?
remains uncontrolled despite optimized treatment
292
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?
293
If 1-2 of the symptom control asthma questions are yes, what is the step?
step up one
294
If 3-4 of the symptom control asthma questions are yes, what is the step?
step up two
295
When is a step down in therapy considered for a patient with asthma?
3 months controlled
296
What is the target oxygen saturation for children, pregnant women, and patients with coexisting heart disease? All other patients?
94-98%
93-95%
297
what is the core pharmacophore of beta2 adrenergic agonists?
substituted beta-phenyl ethylamine
298
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
299
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
300
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
301
Resistance to two enzymes prolong the duration of action of adrenergic agonists. What are they?
COMT and MAO
302
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
303
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
304
Why has formoterol a faster onset of action than salmeterol?
Greater water solubility
305
What is the difference between formoterol and arformoterol?
Arformoterol is the r,r enantoimer
306
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
307
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
308
What is a common structural feature of all anti-muscarinic drugs?
Positive quaternary amine
309
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
310
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
311
Why is prednisone a prodrug?
the carbonyl must be converted to hydroxy in vivo
312
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
313
Which of all topical glucocorticoid drugs has the highest affinity for the glucocorticoid receptor?
mometasone
314
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
315
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
316
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
317
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
318
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
319
Which atomic element that occurs in commonly used contrast media is responsible for their high X-ray density?
iodine
320
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
321
Talc is what type of mineral?
silicate
322
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
323
When injected by intravenous drug users, talc elicits which type of response in the lung?
foreign body response
324
What is the mechanism of toxicity common to doxycycline, other tetracyclines, and bleomycin? What other element is involved?
chelates ions
iron
325
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
326
What is the biological effect of pirfenidone?
decreases fibrosis
327
What type of reactions occur during the metabolism of Pirfenidone?
Benzylic hydroxylation by CYP1A2
Cystolic oxidation to carboxylic acid
328
How is pirfenidone eliminated?
urine
329
What is the target of dornase alfa?
DNA
330
What is the content of Pancrelipase microsphere used for the treatment of cystic fibrosis?
Digestive enzymes and bicarbonate buffer
331
How is CFTR activated, how is it gated?
Activated by PKA
Gated by ATP
332
What is the effect of CRTR correctors versus that potentiators?
Corrects misfolding, prevents degradation of CFTR proteins
333
Which common mutation can be “rescued” with CFTR correctors?
F508del
334
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
335
What is a common structural feature of all cystic fibrosis drugs (answer in lecture recording, not in slides)?
the cyclic ring
336
Name main metabolizing enzymes of the cytochrome P450 superfamily that metabolize ivacaftor, lumacaftor, and elexacaftor?
CYP3A4/5
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