Lecture 5 Flashcards
(142 cards)
1
Q
(Useful Drugs)
B2 Agonist?
A
-Albuterol
-Salmeterol
2
Q
(Useful Drugs)
Leukotriene Antagonist?
A
Montelukast
3
Q
(Useful Drugs)
Muscarinic Antagonist?
A
-Ipratropium
-Tiotropium
4
Q
(Useful Drugs)
Inhaled Corticosteroid?
A
Fluticasone
5
Q
(Useful Drugs)
Monoclonal Anti-IgE antibody?
A
Omalizumab
6
Q
(Useful Drugs)
Rescue?
A
-Albuterol
-Ipratropium
-Tiotropium
7
Q
(Useful Drugs)
Control?
A
-Salmerterol
-Montelukast
-Fluticasone
-Omalizumab
-Ipratropium
-Tiotropium
8
Q
(Useful Drugs)
Asthma?
A
-Ipratropium
-Tiotropium
-Montelukast
-Omalizumab
9
Q
(Useful Drugs)
COPD?
A
-Ipratropium
-Tiotropium
10
Q
(Useful Drugs)
Asthma and COPD (BOTH)?
A
-Albuterol
-Salmeterol
-Flucticasone
11
Q
(Lung Disease)
Increased airway resistance (obstructive lung disease)?
A
-Decreased airflow (zones 0-10, increased resistance) (decreased elasticity)
-Airflow is limited during expiration (hard to get air out, people often hyperinflated)
-Decreased L-CW compliance (restrictive lung disease) (parenchyma fibrosis)
12
Q
(Lung Disease)
Increased airway resistance (obstructive lung disease)?
A
-Decreased airflow (zones 0-10, increased resistance) (decreased elasticity)
-Airflow is limited during expiration (hard to get air out, people often hyperinflated)
-Decreased L-CW compliance (restrictive lung disease) (parenchyma fibrosis)
13
Q
Obstructive Lung Diseases?
A
-Asthma
-Chronic Obstructive Pulmonary Disease
14
Q
(Obstructive Lung Diseases)
Asthma?
A
Spasmodic contraction of smooth muscle in bronchi
15
Q
(Obstructive Lung Diseases)
COPD?
A
-Bronchitis (inflammation of bronchi and bronchioles (increased mucus))
-Emphysema (alveolar destruction)
-Combination
(Bronchitis (mucus) + Emphysema (loss of alveolar))
16
Q
Resistance to airflow in?
A
Conducting Zone (only conducting airway has smooth muscle)
17
Q
Respiratory Zone is mainly for?
A
Gas Exchange
18
Q
Conducting Zone is mainly for?
A
Resistance
19
Q
Further down Airway there is an?
A
Increase in cross-sectional area
20
Q
Further down Airway there is an?
A
Increase in cross-sectional area
21
Q
Factors that Determine Airway Resistance?
A
(SALE)
-Structure of airways
-Airway smooth muscle contraction
-Lumen obstruction (mucus)
-Elasticity of lung parenchyma
22
Q
(Airway smooth muscle contraction)
When receptors activate, they will increase in?
A
Intracellular Ca2+ (Gq) causes smooth muscle contraction
23
Q
(Airway smooth muscle contraction)
No change in alveoli because?
A
Alveoli do not have smooth muscle
24
Q
Autonomic Control of Airway Resistance?
A
1) Provides reflex arc for airway constriction following inhalation of irritants
2) Provides airway dilation during exercise
25
(Autonomic Control of Airway Resistance)
Provides reflex arc for airway constriction following inhalation irritants?
Irritant --> afferent --> medulla --> Para --> constriction to remove irritant
26
(Autonomic Control of Airway Resistance)
Provides airway dilation during exercise?
-Decreased parasympathetic influence
-Increased circulation epinephrine (no direct sympathetic innervation of airway smooth muscle in humans) --> bronchial dilation
27
(Airway Diameter Depends on Retractile Force of Tissue Surrounding Airways in Lung Parenchyma)
As Lung expands, retractile force on airways?
Increase
(as lung expands alveoli pull on airway to keep it open, if we destroy alveoli there is nothing to keep airway from collapsing (emphysema))
28
(Spirometry)
Breathing normal?
vt
29
(Spirometry)
After inhaling, there's still air in lungs?
IRV
30
(Spirometry)
After exhaling, there's still air left in lungs?
FRC
31
(Spirometry)
FRC includes the air you can exhale out forcefully?
ERV
32
(Spirometry)
Air left in your lungs no matter how hard you try to breath out?
RV
33
(Spirometry)
Total amount you can breathe in?
IC
34
(Spirometry)
All air you can force in and out (inhale and exhale as fast as you can) (IC + ERV)?
FVC
35
(Spirometry)
TLC?
Total Lung Capacity
36
(Spirometry)
FRC?
Functional Residual Capacity
37
(Spirometry)
IRV?
Inspiratory Reserve Capacity
38
(Spirometry)
ERV?
Expiratory Reserve Capacity
39
(Spirometry)
FVC?
Forced Vital Capacity
40
(Spirometry)
RV?
Residual Volume
41
(Spirometry)
IC?
Inspiratory Capacity
42
(Spirometry)
Vt?
Tidal Volume
43
(Spirometry)
VC?
Vital Capacity
44
(Volume-Time Curves)
FEV1?
Forced Expired Volume in 1 second
45
(Volume-Time Curves)
FVC?
Inhaled deep + Exhale deep
46
(Volume-Time Curves)
With COPD it's hard to?
Get air out and it will take longer, this will decrease FEV/FVC
47
(Volume-Time Curves)
COPD will ___ FEV?
Decrease FEV
48
(Obstructive Lung Disease)
Emphysema?
-Airspace enlargement destruction (alveoli)
-Decreased FEV1
-Decreased FVC
-Decreased FEV1/FVC ratio
-Decreased elastic recoil reduces structural support for bronchioles. This bronchioles collapse (increase resistance)
49
(Obstructive Lung Disease)
Chronic Bronchitis?
-Mucus gland hyperplasia and hyper secretion, bronchiole fibrosis
-Decreased FEV1
-Decreased FVC
-Decreased FEV1/FVC ratio
-Increased resistance due to clogged bronchioles
50
(Obstructive Lung Disease)
Asthma?
-Smooth muscle hyperplasia/spasmodic contraction, mucus, inflammation, AHR
-Decreased FEV1
-Decreased FVC
-Decreased FEV1/FVC ratio
-Increased resistance due to contracted bronchioles and bronchi
51
(Obstructive Lung Disease)
All will ___ FEV but all for different reasons?
Decrease FEV
52
(Obstructive Lung Disease)
FVC will decrease only with?
Severe Disease
53
(Obstructive Lung Disease)
FVC will decrease only with?
Severe Disease
54
Reversible Airway Obstruction (Bronchospasm)?
Asthma is a common chronic disorder of airways that is complex and characterized by variable and recurring symptoms, airflow obstruction (bronchospasm), bronchial hyperresponsiveness, and an underlying inflammation
55
Spirometry: Assessment of asthmatic airway obstruction (bronchospasm)?
-"Hallmark" of asthma: reversibility with bronchodilator
-Airway obstruction may be absent between "attacks"
56
Measuring Airway Responsiveness?
-We don't want to drop too much and kill someone. So, we look at the amount of methacholine to drop FEV by 20%
-If 0.3 mg/mL of methacholine causes a drop of FEV by 20% = severe asthma
57
Measuring Airway Responsiveness?
-We don't want to drop too much and kill someone. So, we look at the amount of methacholine to drop FEV by 20%
-If 0.3 mg/mL of methacholine causes a drop of FEV by 20% = severe asthma
58
Asthma - Link to Allergy?
-Allergen Sensitization
-Allergen-induced mast cell activation
(allergen detected, presented to T-cell by APC. T-cell instructs by B-cell to produce IgE. Circulating IgE binds to mast cell to release its granules with inflammatory agents)
59
(Remodeling of Lung in Severe Asthma)
Severe Asthmatic Lung?
-Epithelial damage
-Goblet cell hyperplasia
-Smooth muscle hypertrophy and hyperplasia
-Basement membrane thickening
-Collagen deposition
-Submucosal fibrosis
-Angiogenesis
-Mucus plug formation
59
(Remodeling of Lung in Severe Asthma)
Severe Asthmatic Lung?
-Epithelial damage
-Goblet cell hyperplasia
-Smooth muscle hypertrophy and hyperplasia
-Basement membrane thickening
-Collagen deposition
-Submucosal fibrosis
-Angiogenesis
-Mucus plug formation
60
(Role of Vagal Nerve in Respiratory Diseases)
Vagal Afferent?
Sensory nerves that are activated by inflammation, irritants and pollutants
61
(Role of Vagal Nerve in Respiratory Diseases)
Vagal Efferent?
Parasympathetic nerves (cholinergic) innervating smooth muscle and mucosal glands
62
(Role of Vagal Nerve in Respiratory Diseases)
Activation of sensory nerves causes CNS reflexes?
-Cough
-Dyspnea
-Bronchospasm (para)
-Hypersecretion (para)
63
(Role of Vagal Nerve in Respiratory Diseases)
Asthmatic subjects are?
Hyperreflexive to inhaled irritants
64
(Chronic Obstructive Pulmonary Disease - Smoking)
Progressive decrease in lung function?
(clinically relevant in aged population)
-Decreased FEV1
-Limited reversibility
65
(Chronic Obstructive Pulmonary Disease - Smoking)
Presenting symptoms?
-Cough
-Dyspnea (SOB)
66
(Chronic Obstructive Pulmonary Disease - Smoking)
Lung Function?
-Decreased airflow
-Hyperinflation
67
(Chronic Obstructive Pulmonary Disease - Smoking)
Worse with exercise?
Exercise Tolerance Test (6 minute walk)
68
(Chronic Obstructive Pulmonary Disease - Smoking)
Exacerbations (infections) and Airway?
Hyperactivity (limited)
(different than asthma)
69
(Chronic Obstructive Pulmonary Disease - Smoking)
People with COPD tend to?
Die from bacterial infection
70
(Chronic Obstructive Pulmonary Disease - Smoking)
If you start smoking?
-FEV will decrease
-By time 60 cannot breathe out
71
(Chronic Obstructive Pulmonary Disease - Smoking)
Neutrophilia?
Neutrophil elastase, matrix metalloproteinases, reactive oxygen species --> tissue destruction
72
(Chronic Obstructive Pulmonary Disease - Smoking)
Neutrophils will get rid of?
Damaged cells but in the process they damage normal cells
73
(Chronic Obstructive Pulmonary Disease - Smoking)
Neutrophilia (examples of work)?
-Remodeling
-Smooth muscle metaplasia
-Goblet cell metaplasia
-Fibrosis
-Cell death
-Increase Resistance
(Decrease Airflow)
-Decrease Elastic Recoil
-Decrease Gaseous Exchange
74
Chronic Bronchitis?
(blue boaster)
Excessive mucus production, fibrosis of bronchioles
75
Fibrosis/Mucus Blockage?
Increases Resistance and Decreases Airflow
76
Lack of Ventilation?
Hypoxia (blue), edema (bloater)
(mucus stuck in conducting airway so no O2 delivery)
77
Emphysema?
(pink puffer)
Parenchymal/Alveolar damage
78
Decrease Alveoli Structure = ?
-Decrease Elastic Recoil and Decrease Structural Support (Bronchiole collapse)
-Leads to Increase Resistance and Decreased Airflow
79
Lack of Perfusion = only?
Mild Hypoxia (pink)
80
Bronchiole Collapse = ?
Hard to Breathe (puffer)
81
Bronchiole Collapse = ?
Hard to Breathe (puffer)
82
(Chart)
Asthma?
-Usually <40 years (children)
-No History Required
-Common (IgE) (allergy)
-Episodic drop in FEV1
-Increase resistance reversible with B2 agonist
-Increased Hyperactivity
-Frequent family history
-Cough (often dry)
-Eosinophils, Mast Cells, Basophils
-CD4+, Th2 cells, B cells
83
(Chart)
COPD?
-Usually >40 years
->10 pack years of smoking
-No correlated with allergies
-Chronic drop in FEV1
-Minimal increase resistance reversible with B2 agonist
-Small increase in hyperactivity
-Cough (often wet)
-Neutrophils, Macrophages
-CD8+, Tcyt cells
84
Bronchitis?
Gap is filled with mucus
85
Asthma?
Gap closed with bronchoconstriction
86
Emphysema?
Lost structural support, bronchi collapse
87
Bronchitis, Asthma, and Emphysema all?
Increase Resistance
88
Bronchitis, Asthma, and Emphysema all?
Increase Resistance
89
(Obstructive Disease Pharmacological Treatments)
Primarily concerned with increasing?
Airflow/decreasing resistance
90
(Obstructive Disease Pharmacological Treatments)
Actively cause bronchodilation (beta-adrenoceptor agonists) B2?
Albuterol, Salmetrol
91
(Obstructive Disease Pharmacological Treatments)
Inhibit specific inflammatory mediators (leukotriene and muscarinic antagonists)?
Montelukast, Ipratopium, Tiotropium
92
(Obstructive Disease Pharmacological Treatments)
Reduce inflammation (corticosteroids)?
Fluticasone
93
(Obstructive Disease Pharmacological Treatments)
Prevent inflammation (anti-IgE antibodies (for asthma only))?
Omalizumab
94
(Obstructive Disease Pharmacological Treatments)
Some are used for?
Rescue from a respiratory attack, some are used for control of symptoms
95
3 Things for Patient Education?
1) Lifestyle changes (quit smoking)
2) Compliance
3) Control of Environment (allergens, mold, pollutants)
96
(B Adrenoceptor Agonists)
B2 selective ligands?
Albuterol, Salmeterol (inhalation, oral)
97
(B Adrenoceptor Agonists)
MOA?
-Activation of B2 adrenoceptors on bronchial smooth muscle (increase cAMP) --> relaxation --> bronchodilation
98
(B Adrenoceptor Agonists)
Therapeutic Uses?
-Short-acting (albuterol) (rescue for asthma and COPD)
-Long-acting (LABA) (salmeterol)
(control for asthma and COPD)
-Salmeterol (everyday use)
99
(B Adrenoceptor Agonists)
Side Effect?
Tachycardia
(B2 also in Heart and these drugs are not completely B1 inactive)
100
(B Adrenoceptor Agonists)
Asthma Attack?
Give Albuterol
101
(B Adrenoceptor Agonists directly relax Bronchial Smooth Muscle)
MOA?
(increase cAMP --> relaxation --> bronchodilation)
1) Facilitates sequestration of Ca2+
2) Inactivates MLCK
3) Inactivates MLC20
102
(B Adrenoceptor Agonists directly relax Bronchial Smooth Muscle)
PKA inhibits?
Kinase
103
(B Adrenoceptor Agonists directly relax Bronchial Smooth Muscle)
Myosin light chain phosphatase, dephosphorylate myosin?
No cont.
104
(Cysteinyl Leukotrienes)
Originally known as slow reacting substances of anaphylaxis de novo synthesis occurs in?
Mast cells and basophils following allergen-binding IgE de novo synthesis also in eosinophils and neutrophils
105
(Cysteinyl Leukotrienes)
Pharmacology?
-G protein coupled receptors CysLT1 and CysTL2
-Both are Gq coupled - phospholipase C activation --> IP3 and DAG production, increase Ca2+ and PKC
-All cysteinyl leukotrienes are effective at both receptors
106
(Cysteinyl Leukotrienes)
Receptor Expression?
Bronchial smooth muscle (CysLT1)
(causes contraction --> bronchospasm)
(increase hyperplasia)
107
(Cysteinyl Leukotrienes)
LTD has?
Highest Concentration
108
(Leukotriene Antagonist)
Montelukast given?
Oral
109
(Leukotriene Antagonist)
Montelukast MOA?
-CysTL1 antagonist
-Prevents Sys-LT-induced bronchospasm, decrease immune cell infiltration, no decrease AHR, very mild reversal of remodeling
110
(Leukotriene Antagonist)
Montelukast Therapeutic Uses?
-Control for asthma
-Not for COPD because you don't produce LT
111
Leukotriene Antagonist is a ___ for asthma?
Control
112
Muscarinic Antagonists?
-Ipratopium bromide (non-selective)
-Tiotropiumbromide (M1, M3 but not M2 inhibitor) - quaternary amine derivates of atropine (quart can't move = less SE)
113
(Muscarinic Antagonists)
Given?
Inhalation
114
(Muscarinic Antagonists)
MOA?
-Blocks acetylcholine-induced activation of muscarinic receptors on: (airway smooth muscle (M3) - decrease bronchospasm) (epithelial mucosal glands (M3) - decrease mucus secretion)
115
(Muscarinic Antagonists)
Therapeutic Uses?
-Rescue for asthma
-Control for COPD
116
(Muscarinic Antagonists)
Therapeutic Uses?
-Rescue for asthma
-Control for COPD
117
Inhaled Corticosteroids?
Analogs of corticosterone, steroid hormone (adrenal cortex) ex. Budesonide, Fluticasone
118
(Inhaled Corticosteroids)
Given?
Nasal or Inhalation
119
(Inhaled Corticosteroids)
MOA?
Anti-inflammatory, decrease infiltration of eosinophils/basophils/mast cells, mild reversal of remodeling
120
(Inhaled Corticosteroids)
Therapeutic Uses?
-Control for asthma (inhalation, nasal)
-Control for COPD - limited relief
121
(Corticosteroid: Mechanism of Action)
In multiple cell types including?
Epithelial cells, lymphocytes, granulocytes, mast cells, smooth muscle, dendrites cells and fibroblasts
122
(Corticosteroid: Mechanism of Action)
Steroid molecule binds to?
Cytoplasmic glucocorticoid receptor (GR), dimerizes, enters nucleus, binds to DNA at specific sites (glucocorticoid response elements):
(decrease pro-inflammatory protein production)
(increase anti-inflammatory protein production)
123
(Corticosteroid: Mechanism of Action)
Modulation of Protein expression is?
Slow-onset (>12 hours)
124
(Corticosteroid: Mechanism of Action)
Slow Onset?
Not a rescue drug
125
(Corticosteroid: Mechanism of Action)
Decrease de novo transcription of?
Pro-inflammatory proteins: cytokines (ex. IL-4 and IL-5) and chemokine
126
(Corticosteroid: Mechanism of Action)
Increase transcription of IkB?
A potent anti-inflammatory protein that inhibits NFkB (pleiotropic gene transcription factor which produces TNFa, iNOS, COX2, adhesion molecules, IL-2)
127
(Corticosteroid: Mechanism of Action)
Inhibits AP-1?
Pleotropic gene transcription factor which produces collagenase, IL-2
128
(Corticosteroid: Mechanism of Action)
Increase transcription of?
-B2, Adrenoceptor
-Lipocortin 1 (inhibitor of PLA2)
129
(Corticosteroid: Mechanism of Action - Asthma)
Asthma?
-Steroids decrease airway eosinophilia
-Steroids decrease IgE production from B cells and inhibit mast cell degranulation
130
(Corticosteroid: Mechanism of Action - Asthma)
COPD?
-Corticosteroids have little effect on neutrophilic
-Corticosteroids may increase lung defense against neutrophil elastase
-Corticosteroids may decrease activity of neutrophil-derived metalloproteinases
-Corticosteroids have no effect on MORTALITY
131
(Corticosteroid: Mechanism of Action - Asthma)
COPD?
-Corticosteroids have little effect on neutrophilic
-Corticosteroids may increase lung defense against neutrophil elastase
-Corticosteroids may decrease activity of neutrophil-derived metalloproteinases
-Corticosteroids have no effect on MORTALITY
132
Corticosteroid: Side Effects?
Due to GR signaling/MR signaling (mineralocorticoid/aldosterone)/both in multiple tissues
133
Corticosteroid Inhalation Side Effects?
-Inhalation decreases systemic effects
-Increases risk of infection (oropharyngeal candidiasis)
(COPD: bacterial lung infection - pneumonia)
134
Corticosteroid Oral (systemic) Side Effects?
-Hyperglycemia
-Dyslipidemia
-Hypertension
-Osteoporosis
-Cataracts
-Glaucoma
-Teratogenic
135
(Anti-IgE Antibodies)
Omalizumab given?
Subcutaneous injection
136
(Anti-IgE Antibodies)
Omalizumab?
Monoclonal antibody (IgE)
137
(Anti-IgE Antibodies)
Omalizumab MOA?
-Binds to free IgE (Fc region), promotes destruction
-Decreases IgE from binding to FCeR1 and FCeR2
-Decreases expression of FCeR1 on mast cells/basophils
-Decreases allergen-induced IgE crosslinking on mast cells/basophils
138
Anti-IgE Antibodies MOA?
-Prevents allergen-induced bronchospasm, decreased immune cell infiltration, decreased exacerbations, no decreased AHR, effect on remodeling is unclear
139
Anti-IgE Antibodies Therapeutic Uses?
Control for severe, steroid-resistant asthma
140
Anti-IgE Antibodies Rate of Onset?
-Circulating IgE destroyed in hours/days
-Takes more than a week for mat cell-attached IgE to reduce
141
Anti-IgE Antibodies _____ only?
Control only
