Test 3: Wk13: 1 Airway Pharmacology - Salisbury Flashcards
1
Q
treatment of choice for asthma
A
B2 adrenergic agonists
2
Q
B2 adrenergic agonists are used for
A
rescue bronchodilators in asthma
3
Q
3 Selective B2 Agonists
A
albuterol
pirbuterol
terbutaline
4
Q
Long acting B2 agonists function
A
bronchodilation and bronchoprotection for more than 12 hrs
dose 2x daily
5
Q
3 once daily B2 agonists
A
indacaterol
vilanterol
olodaterol
6
Q
B2 agonists direct bronchodilator MOA
A
B2 expressed on bronchial SMCs
Gs adenylyl cyclase CAMP
bronchial SM relaxation
7
Q
B2 Agonists Indirect bronchodilator MOA
A
Gs adenylyl cyclase cAMP PKA
mast cells decrease mediator release
decrease ACH release by cholinergic nerves
8
Q
B2 Agonists anti-inflammatory effects
A
decrease mast cell mediator release and microvascular leakage
9
Q
do B2 agonists help with chronic inflammation
A
no, corticosteroids still needed
10
Q
SABAs stands for
A
Inhaled short acting B2 Agonists
11
Q
Oral B2 agonists
A
increased side effects
resistant to COMT and MAO
useful in pts who cant use MDI
12
Q
3 LABAs that have Bronchodilator action of more than 12 h and also protect
against bronchoconstriction for a similar period
A
salmeterol
formoterol
arformoterol
13
Q
3 LABAs that have Duration of over 24 h (effective in COPD)
A
Indacaterol, vilanterol, and olodaterol
14
Q
— can be combined with anticholinergics or ICSs
A
LABAs
15
Q
can LABAs be used alone in asthma
A
no, they do not treat underlying chronic inflammation
16
Q
in Asthma LABAs must be used with
A
ICSs
17
Q
2 B2 Combination inhalers
A
fluticasone/salmeterol
budesonide/formoterol
18
Q
Combination inhalers ensure — and allows for
A
Ensures they are delivered simultaneously to the same
cells in the airway this allows beneficial molecular
interactions between LABAs and ICS to occur.
19
Q
ICS upregulate — receptors on bronchial SMCs
A
B2
20
Q
Combination inhalers are used in
A
asthma and COPD
21
Q
B2 agonists tolerance
A
occurs in non airway tissues
in asthmatic pts tolerance to the bronchodilator effects B2 agonists has not usually been found
22
Q
5 Side effects of B2 agonists
A
Muscle tremor Tachycardia Hypokalemia Restlessness Metabolic effects
23
Q
Theophylline therapeutic index
A
narrow
24
Q
Theophylline MOA (4)
A
Nonselective phosphodiesterase (PDE) inhibitor
Adenosine receptor antagonism
interleukin 10 release
inhibition of trscrptn factor NF-kB
25
Theophylline PDE inhibitor MOA
```
Nonselective phosphodiesterase (PDE) inhibitor (↑ cAMP and cGMP→ smooth muscle cell relaxation,
PDE3, PDE4 and PDE5
```
26
Theophylline affects multiple on eosinophils
decrease number
| increase apoptosis
27
Theophylline affects multiple on T-lymphocyte
decrease cytokines
28
Theophylline affects on Mast Cells
decrease mediators
29
Theophylline affects multiple on macrophages
decrease cytokines
30
Theophylline affects on Airway SMCs
bronchodilation
31
Theophylline affects on endothelial cells
decrease leak
32
Theophylline affects on respiratory skeletal muscles
possibly increase strength
33
Theophylline therapeutic range
5-15 mg/L
34
Theophylline metabolized by
lover, CYP1A2
35
Increased Clearance of Theophylline
CYP1A2 induction
36
Decreased Clearance of Theophylline
CYP1A2 inhibition
37
Theophylline Asthma
Reserved for patients who fail to respond to, or are
intolerant of, ꞵagonists.
Add to low dose ICS (better response than doubling the dose of
ICS)
38
Theophylline COPD:
Still used as a bronchodilator
39
Theophylline side effects (6)
```
Nausea and vomiting
Headaches
Gastric discomfort
Diuresis
Cardiac arrythmias
Epileptic seizures
```
40
Muscarinic Cholinergic Antagonists Inhibit ---receptors on bronchial smooth muscle and lead to a reduction in the --- pathway
M3
M3 Gq PLC IP3 Ca2+
41
Muscarinic Receptor Antagonists clinical effects
reduce bronchoconstriction
reduce traheobronchial mucus secretion
42
Cholinergic antagonists have --- effect on mast cells or the chronic inflammatory response
little
43
Muscarinic Receptor Antagonists Asthma:
anticholinergic agents are less effective than ꞵ2 agonists
44
Muscarinic Receptor Antagonists COPD:
anticholinergic drugs are as effective or more effective than ꞵ2 agonists
45
Anticholinergic drugs have an additive effect when combined with ---
ꞵ2 agonists
46
3 Therapeutic Choices for Muscarinic Receptor Antagonists
Ipratropium (MDI)
Tiotropium (DPI)
Glycopyrronium bromide (DPI)
47
Muscarinic Receptor Antagonists Combination Inhalers
anticholinergic and ꞵ2 agonists:
| albuterol/ipratropium
48
Muscarinic Receptor Antagonists Adverse effects:
generally well tolerated
systemic effects uncommon
bitter taste w/ ipratropium
Nebulized ipratropium may precipitate glaucoma
49
--- has revolutionized the treatment of chronic
| asthma
ICSs
50
1st line therapy for asthma
ICSs
51
ICSs in COPD
much less effective in COPD and should only be
used in patients with severe disease who have frequent
exacerbations.
52
Corticosteroids MOA
anti-inflammatory effects
| Ligand activated transcription factor
53
Corticosteroids effect on eosinophils
decease numbers
| increase apoptosis
54
Corticosteroids effect on T-lymphocytes
decease cytokinesis
55
Corticosteroids effect on mast cells
decrease numbers
56
Corticosteroids effect on macrophages
decrease cytokines
57
Corticosteroids effect on dendritic cells
decrease numbers
58
Corticosteroids effect on epithelial cells
decrease cytokines
| decrease mediators
59
Corticosteroids effect on endothelial cells
decrease leak
60
Corticosteroids effect on airway SMCs
increase B2 receptors
| decrease cytokines
61
Corticosteroids effect on mucus glands
decrease mucus secretion
62
Corticosteroids have --- direct effect on contractile responses of airway smooth muscle thus they are not rescue bronchodilator agents for asthma
no
they are not rescue bronchodilator agents for asthma
63
improvement in lung function after ICSs is due to (3)
↓ chronic airway inflammation
↓ edema
↓ airway hyperresponsiveness.
64
ICSs Rapid anti inflammatory effects
reduce airway hyperresponsiveness and inflammatory
| mediator concentrations within a few hours.
65
ICSs achieve maximal effects on airway in
several weeks or months
66
Corticosteroids suppress inflammation in the airways but
do not cure the underlying disease.
67
Corticosteroids potentiate the effects of β agonists on bronchial smooth muscle and
prevent and reverse β receptor desensitization in airways.
68
Corticosteroids increase the transcription
of the β 2 receptor gene in human lung tissue
69
--- reduces ICSs from reaching systemic circulation
spacer chamer
70
ICSs on COPD
respond if they have asthma
no effect on progression
no effect on mortality
reduce exacerbations in severe COPD
71
Intravenous corticosteroids:
A cute asthma if lung function is less than 30%
predicted and in patients who show no significant
improvement with nebulized β 2 agonist.
72
--- is the steroid of choice because it has
Hydrocortisone
is the steroid of choice because it has
the most rapid onset (5 6 h after administration),
compared with 8 h with prednisolone.
73
Local Side Effects of ICSs
Dysphonia
Oropharyngeal candidiasis
Cough
74
Corticosteroids Systemic effects - long term oral corticosteroid
treatment (7)
HPA Axis suppression
fluid retention and wt gain
capillary fragility - hypertension
diabetes, cataracts, psychosis
Metabolic abnormalities
75
Corticosteroids Therapeutic Choices
beclomethasone, triamcinolone, flunisolide, budesonide,
hemihydrate, fluticasone propionate, mometasone
furoate, ciclesonide , and fluticasone furoate.
76
2 Cromones drugs
Cromolyn, nedocromil
77
Cromones uses
Prophylactic anti inflammatory agents (inhalation delivery)
78
Cromones action
mast cell stabilizers
79
oral PDE4 inhibitor
Rofumilast
80
Phosphodiesterase Inhibitor action
relax smooth muscle and inhibit inflammatory cells by increasing the levels of cAMP
81
Roflumilast approved for
severe COPD
82
Roflumilast side effects
diarrhea, headaches and nausea (limits its efficacy)
83
Mediator antagonists
antihistamines
84
Antihistamines evidence
since multiple mediators in action, inhibiting just H1 alone isnt enough to have an effect
85
Cys-LTs cause
they induce bronchoconstriction, airway
hyperresponsiveness, plasma exudation, mucus
secretion, and eosinophilic inflammation
86
5-LO Inhibitors Drug and MOA
Zileuton; inhibits 5-lipoxyfenase
87
LT antagonists (3)
Montelukast
Pranlukast
Zafirlukast
88
Antileukotrienes indication
mild to moderate asthma: improved lung function and reduced the use of a β 2 agonist
89
Antileukotrienes compared to ICSs
Antileukotrienes are less effective
90
Antileukotrienes is a benefit in
allergic rhinitis
91
Antileukotrienes use in children
yes
92
Antileukotrienes and aspirin sensitivity
Should be beneficial in patients with aspirin sensitive
| asthma (block the airway response to aspirin challenge)
93
Antileukotrienes and exercise induced asthma
effective
94
Antileukotrienes in COPD
not effective
95
Zileuton, zafirlukast and montelukast adverse effects
rare cases hepatic dysfunction
Churg Strass syndrome w/ zafirlukast and montelukast
96
Immunomodulatory Therapies
Anti IgE receptor therapy
97
is a humanized monoclonal antibody that binds
| free IgE
Omalizumab
98
Anti IgE receptor therapy prevents
prevents the binding of IgE to high affinity IgE receptors
(FcεR1) on mast cells and thus prevents their activation by
allergens
99
Omalizumab used in
pts w/ severe asthma
100
Omalizumab reduces requirement of
oral and or ICSs
101
Omalizumab reduces
asthma exacerbations
102
Allergic Rhinitis tx
Antihistamines
Ipratropium
```
Adrenergic agonists (Oxymetazoline, Phenylephrine,
Pseudoephedrine)
```
Montelukast
Corticosteroids (nasal spray)
103
Antitussives
Opioids
104
Opioids are agonists of
Agonists of the mu (µ) opioid receptor.
105
Opioids mechanism
μ opioid receptors in
| medullary cough center to suppress cough
106
--- opioid is commonly used to suppress cough
Codeine
107
Opioids Adverse effects
sedation, constipation, opioid induced respiratory depression
108
Dextromethorphan
Antitussive
Centrally active NMDA antagonist
109
Dextromethorphan acts in
Acts in medullary cough center to suppress cough
110
Dextromethorphan adverse effects
Hallucinations at high concentrations
abuse potential
111
BENZONATATE
Antitussives
Inhibits stretch or cough receptors of vagal afferent fibers, which are located in the respiratory passages, lungs, and pleura
112
Suppresses cough through a peripheral action.
BENZONATATE
113
BENZONATATE adverse effect
Adverse effects: Dizziness
114
Expectorant
Guaifenesin
115
Guaifenesin action
•
| Reduces the viscosity of mucus in airway
116
Guaifenesin adverse effect
Adverse effect: Nausea
117
Mucolytics (2)
N Acetylcysteine
Dornase Alfa
118
N Acetylcysteine action
Acetylcysteine has a free sulfhydryl group that interacts
with disulfide bonds in mucus proteins (“opens up”
mucus proteins reduces Airway mucus viscosity)
119
N Acetylcysteine is also useful for treating
cystic fibrosis
120
N Acetylcysteine administration
nebulizer
121
Dornase Alfa action
Is a DNase that reduces Airway mucus viscosity in patients with cystic fibrosis by breaking the long extracellular DNA molecules in mucus into smaller DNA fragments
122
Dornase Alfa indication
cystic fibrosis
123
Dornase Alfa adverse effect
Dyspnea
