Respiratory (Exam 3) Flashcards
1
Q
Outcome of smoking on public
A
Loss of tax dollars
2
Q
Indications of human health
A
Life expectancy and infant mortality
3
Q
Indications of human health vary greatly between…
A
Developed and developing countries
4
Q
Lower respiratory tract
A
Includes trachea, bronchi, and alveoli in the lungs
Tuberculosis bacteria settle and cause infection
5
Q
Upper respiratory tract
A
Includes nose, throat, and sinuses
6
Q
Upper respiratory tract infections
A
Sinusitis, Allergic rhinitis, stridor, tonsillitis, influenza, croup, whooping cough
7
Q
Lower respiratory infections
A
Acute bronchitis, pneumonia, SARS, tuberculosis
8
Q
Structure and function of respiratory system
A
Surface area
Blood-gas barrier
Cell types
9
Q
Largest surface area of the body?
A
Alveolar
Substantial surface for toxicant contact and absorption
10
Q
Respiratory airways and alveolar epithelium are in…
A
direct contact with environmental toxicants in air
11
Q
What separates the blood from contaminated environmental air?
A
Alveolar epithelium and capillary endothelium
12
Q
Cells types involved in pulmonary toxicity
A
Type-I
Type-II
Clara cells
Alveolar macrophages
Endothelial cells
13
Q
Normal lung
A
Thin walls in upper and lower airways allow normal exchange of gases between blood vessels and airspace
14
Q
Diseased upper airway of lungs
A
Produces influx of inflammatory cells
Increased fibrosis
Constriction of bronchiolar airways
15
Q
Diseased lower airway of lungs
A
Fibroblasts and mononuclear inflammatory cells lead to collagen deposits and thickening of lung walls
16
Q
Clara cells
A
Non-ciliated rounded secretory cells
Target for pulmonary toxicants
17
Q
How are Clara cells distinguished?
A
By smooth rounded “domes” which project into bronchiolar lumen
18
Q
Function of Type I alveolar cells
A
Line alveolar spaces
Only barrier between air and capillary endothelium
19
Q
Where are Clara cells located?
A
Only in small bronchioles
20
Q
Functions of Type II alveolar cells
A
Synthesize surfactant
Serve as Stem cells for Type I alveolar epithelium
Form part of blood-gas barrier
21
Q
Functions of alveolar macrophages
A
Phagocytosis
Fibrosis in lungs
22
Q
How do alveolar macrophages lead to fibrosis?
A
When overload, they die and release acid hydrolases and phospholipases
These stimulate fibroblasts –> Fibrosis
23
Q
How do Type II cells serve as stem cells?
A
Type I cells destroyed
Type II proliferate to cover alveolar surface
24
Q
How many days to replace type I cells with type II?
A
2 days
25
Immature Type II cells
Cuboidal and transfer oxygen more slowly than type I
26
Functions of Clara cells
Secretions
Xenobiotic metabolism via CYP450
27
CYP450
Found in high concentration in Clara cells
28
Functions of endothelial cells (5)
Formation of blood-gas diffusion barrier
Maintenance of active transport
Uptake & metabolism of pesticides
Angiotensin I --> angiotensin II
Synthesis & metabolism of prostaglandins
29
Upper respiratory disorders
Allergies
Bronchitis
30
Obstructive Lung Diseases
Asthma
COPD
Cystic Fibrosis
31
Viruses of Upper Respiratory Tract (CRRABCHIP)
Coxsack
Rhinovirus
Respiratory Syncytial
Adenovirus
Bocavirus
Coronavirus
Herpesvirus
Influenza
Parainfluenza
32
Viruses of Lower Respiratory Tract (PRAMBIS)
Parainfluenza
Respiratory Syncytial
Adenovirus
Metapneumovirus
Bocavirus
Influenza
SARS-COV-2
33
How are upper respiratory disorders characterized?
By infection and hypersensitivity of specific areas
34
Symptoms of upper respiratory disorders
Runny nose
Sore throat
Cough
Breathing difficulty and lethargy
35
Asthma is triggered by
environmental variables
allergens, pollutants, exercise
36
Symptoms of asthma
shortness of breath
contraction of bronchiolar smooth muscle
37
Mechanisms of upper respiratory disorders
Swelling
Increased vascular permeability
Increased secretions
38
Mechanisms of Asthma
Activation of mast cells
Infiltration of eosinophils and helper T cells (TH2)
39
Which two disorders are characterized by chronic inflammation of airway?
Asthma
COPD
40
Symptoms of COPD
Shortness of breath
Progressive destruction of lung parenchyma of small airway
41
Mechanisms of COPD
Infiltration of Neutrophils, macrophages and cytotoxic T-cells
42
Respiratory Disease Controlling Agents
Meds used to relieve, treat, or prevent respiratory diseases such as asthma, chronic bronchitis, COPD, or pneumonia
43
Inhalation Respiratory Agents
Deliver meds directly to lungs
Meds act directly on lung tissues
Minimal systemic side effects
44
Cystic Fibrosis (CF)
Autosomal-recessive inherited disease
45
What does CF cause?
Defective Cl- secretion in the lung
46
What is defective CL- secretion caused by?
Mutations of the CFTR Cl- channel
47
Result of CFTR mutation
Thick dehydrated mucus and chronic bacterial infections
48
How many mutations in CFTR gene have been identified?
1600
49
Therapies for CF target...
downstream consequences that are secondary to loss of CFTR Cl- channel function
50
Goals of CF treatment
Prevent/control infections
Remove & loosen mucus
Treat/prevent intestinal blockage
Provide nutrition
51
CFTR modulators
Elexacaftor
Ivacaftor
Tezacaftor
Lumacaftor
52
Trikafta
(elexacaftor, ivacaftor, tezacaftor)
Approved for age 12 and older
53
Symdeko
(tezacaftor, ivacaftor)
Approved for age 6 and older
54
Orkambi
(lumacaftor, ivacaftor)
Approved for age 2 and older
55
Kalydeco
(Ivacaftor)
Approved for 6 months and older
56
CFTR modulator therapies correct...
malfunctioning protein made by CFTR gene
57
Do CFTR medications work for all CF patients?
NO!
Only for specific mutations
58
Precursor to Histamine
Histadine
59
Autacoids
Do NOT act on cholinoreceptors or adenoreceptors but have effects on smooth muscle
60
Most important amine autacoids
Histamine and serotonin
61
First generation H1 blocker
Diphenhydramine
61
Ergot alkaloids
Heterogeneous group of drugs that interact with serotonin, dopamine, and alpha receptors
61
Second generation H1 blocker
Cetirizine
62
H2 blocker
Cimetidine
63
5-HT1 agonist
Sumatriptan
64
5-HT4 partial agonist
Tegaserod
65
5-HT2 antagonist
Ketanserin
66
5-HT3 antagonist
Ondansetron
67
5-HT2 agonist in obesity
Lorcaserin
68
Classes of histamine receptors
H1-H4
69
Where are H1 and H2 receptors distributed?
Periphery and central nervous system
70
H1 receptors
Blocked selectively by classical 'antihistamines'
71
Where are H1 receptors found?
Endothelial cells
72
Are H1 receptors direct or indirect vasodilators?
INDIRECT
73
Are H2 receptors direct or indirect vasodilators?
DIRECT
74
H2 receptors
stimulate gastric acid secretion
75
Where are H2 receptors found?
Gastric mucosa
Cardiac muscle
Mast cells
Brain
76
H3 receptors are
presynaptic autoreceptors
77
H3 receptors decrease...
release of histamine
PROMOTE SLEEP
78
Where are H4 receptors expressed?
Cells of hematopoietic lineage
79
What do H4 receptors do?
Mediate immune function
80
Low affinity histamine receptors
H1 and H2
81
High affinity histamine receptors
H3 and H4
82
H1 partially selective antagonists or inverse agonists
Mepyramine
Triprolidine
Cetirizine
83
H2 partially selective antagonists or inverse agonists
Cimetidine
Ranitidine
Nizatidine
84
H3 partially selective antagonists or inverse agonists
Thioperamide
Iodophenpropit
Clobenpropit
Tiprolisant
Proxyfan
85
H4 partially selective antagonists or inverse agonists
Thioperamide
86
Distribution of H1 receptors
Smooth muscle
Endothelium
Brain
87
Distribution of H2 receptors
Gastric mucosa
Cardiac muscle
Mast cells
Brain
88
Distribution of H3 receptors
Presynaptic autoreceptor
89
Distribution of H4 receptors
Eosinophils
Neutrophils
CD4 T cells
90
H1 receptor antagonists
Competitive inhibition of H1 receptor in blood vessels of nasal mucosa
91
1st Gen H1 receptor antagonists
Clemastine
Chlorpheniramine
Cyproheptadine
Diphenhydramine
Doxylamine
Hydroxyzine
Ketotifen
Promethazine
92
2nd Gen H1 receptor antagonists
Terfenadine
Loratadine (Claratin)
Ceterizine (Zyrtec)
93
3rd Gen H1 receptor antagonists
Desloratadine
Fexofenadine (Allegra)
Levocetirizine
94
Which H1 receptor antagonists have anti-muscarinic effects?
1st Gens
Diphenhydramine
Bromopheniramine
Chlorpheniramine
Carbinoxamine
95
Bronchiolar Smooth Muscle Relaxation Pathway
Epinephrine binds to B2-receptor, activates AC, ATP activates cAMP --> Protein Kinase A --> decrease in Ca+
96
leukotrienes
slow reacting substance of anaphylaxis
97
examples of leukotriene inhibitors
zileuton
montelukast
pranlukast
zafirlukast
98
zileuton MOA
inhibitor of 5-lipoxygenase activity in LOX pathway
99
Adrenergic alpha receptor agonists
Phenylephrine
Ephedrine
Psuedoephedrine
100
montelukast/pranlukast/zafirlukast MOA
inhibit CYSLTR1 which is a target of cysteinyl leukotrienes
101
Psuedoephrdrine is a _____ of ephedrine.
Stereoisomer
102
why is zileuton least prescribed?
due to liver toxicity
103
does the leukotriene receptor antagonists have toxicity?
little
104
Ephedrine and Psuedoephedrine Pharmacodynamics
Mixed acting sympathomimetics
Increase NE release
a1 receptor agonist
105
what happens when cysteinyl leukotrienes bind to CYSLTR1?
constriction of airway smooth muscle
increased vascular permeability
decreased mucocilliary clearance
mucus hypersecretion
106
Phenylephrine
Selective a1 receptor agonist
107
inhaled corticosteroid MOA
cortisol transported by glucocorticoid receptor and enters nucleus
GRE interacts with DNA and alters transcription
108
Sympathomimetic Agents Actions
Decrease resistance to airflow by decreasing volume of nasal mucosa
Activation of alpha receptors that have erectile characteristics
Decrease mucous secretions
109
examples of inhaled corticosteroids
beclomethasone
flunisolide
fluticasone
budesonide
mometasone
110
where do inhaled corticosteroids bind?
glucocorticoid receptor
111
when inhaled corticosteroids bind to the GR, what happens?
induction of anti inflammatory genes
inhibition of pro inflammatory genes
modification of cellular protein transcription
112
when is peak action of inhaled corticosteroids?
hours to days
113
are inhaled corticosteroids used for acute relief?
NO
114
inhaled corticosteroid doses _____ and are initially used to cause _________ for airway clearance
vary
bursts
115
most important action of inhaled corticosteroids
inhibition of the infiltration of asthmatic airways by lymphocytes, eosinophils, and mast cells
116
Sympathomimetic Agents therapeutic applications
Used in OTC remedies for upper respiratory tract disorders
117
therapeutic indications for inhaled corticosteroids
COPD and asthma
118
short term adverse effects of inhaled corticosteroids
anaphylaxis (beclomethasone)
localized opportunistic infections
SOB
mood alterations
restlessness
dry mouth
119
Ephedrine adverse effects
CNS effects
Tachycardia
Hypertension
120
Pseudoephedrine adverse effects
less potent tachycardia
increased BP
CNS stimulation
121
long term adverse effects of inhaled corticosteroids
moon face
fluid retention
weight gain
osteoporosis
glomerulonephritis
122
mucokinetic therapy also known as
mucolytics
mucous controlling agents
123
Phenylephrine adverse effects
Increased BP
Vasoconstriction
124
example of mucolytics
n-acetylcysteine
Pulmozyme (dornase-a)
125
Where is histaminergic system localized?
Posterior hypothalamus
126
MOA of mucolytics
breaks down disulfide bonds in mucoproteins
127
therapeutic indications for mucolytics
thins abnormally thick mucus in CF and pulmonary fibrosis
128
adverse effects of mucolytics
wheezing
airway obstruction due to liquefaction of secretions
nausea and rhinorrhea
odor (hydrogen sulfide)
incompatibility with anti infective compounds
129
Histamine acting via H1 or H3 receptors
Regulation of sleep-wakefulness
130
omalizumab
recombinant, humanized mAB against human IgE
monoclonal antibody
131
What induces wakefulness?
Histamine
H1 receptor agonists
132
omalizumab MOA
binds to free IgE so they cannot bind to mast cell and cause inflammation/trigger an effect
133
What promotes sleep?
H1 receptor antagonists
134
Pulmozyme MOA
recombinant human deoxyribonuclease I (rhDNase)
135
H3 receptor functions as...
Autoreceptor
Regulates synthesis/release of histamine
136
rhDNAse
selectively cleaves DNA
hydrolyzes the DNA present in sputum/mucus of CF and reduces viscosity in lungs
137
Histaminergic neurons display max activity during...
State of vigilance
138
adverse effects of pulmozyme
pharyngitis
laryngitis
rash
chest pain
139
dimetapp day vs dimetapp night
both have phenylephrine (decongestant)
day - brompheniramine (antihistamine) and dextromethorphan (cough suppressant)
night - diphenhydramine (antihistamine and cough suppressant)
140
Histaminergic neurons cease activity during
NREM and REM sleep
141
Classification of beta2 agonists
SABAs
LABAs
ultra-LABAs
142
DayQuil vs nyquil
both - acetaminophen and dextromethorphan
day - phenylephrine
night - doxylamine
143
Which class of beta2 agonists has shortest half life?
SABAs
Immediate symptomatic relief
144
robitussin DM
dextromethorphan (antitussive) and guaifenesin (thins mucus)
145
Prolonged duration of beta2 agonists is achievable by
decreasing susceptibility of agonists to COMT and MAOs
146
Robitussin Max strength DM day vs night
both - dextromethorphan
day - guaifenesin
night - doxylamine
147
Adrenergic beta receptor agonists
Bronchodilators dilate bronchi by direct action on adrenoreceptor on bronchial smooth muscle and relac muscle
148
Benadryl allergy (my fav)
diphenhydramine (antihistamine)
149
Benadryl Allergy Plus congestion
diphenhydramine (antihistamine)
phenylephrine (decongestant)
150
Benadryl Itch Stopping Cream
diphenhydramine (antihistamine)
zinc (skin protectant)
151
Benadryl itch cooling gel
camphor
152
besides being an antihistamine, Benadryl is also classified as an
antitussive (cough suppressant)
because you can't cough when your passed out cold!
153
Non-selctive Adrenergic beta receptor agonists
Epinephrine
Isoproterenol
154
Sympathomimetic agents therapeutics indication
Asthma
155
Sympathomimetic agents adverse effects
Cardiovascular
Tachycardia
Hypertension
Somatic tremor
Nausea and insomnia
156
Common SABAs
Salbutamol (albuterol)
Terbutaline
Levalbuterol
Pirbuterol
157
Common LABAs
Salmeterol
Formoterol
158
Common Ultra-LABAs
Indacaterol
Olodaerol
Vilanterol
Formoterol
159
Bronchiolar Smooth Muscle Contraction Pathway
ACh binds to M2/M3 receptor to release PLC --> cleaved by PIP2 into DAG and IP3
DAG --> PKC
IP3 --> increases Ca+
160
Anticholinergic Agents
Ipratropium
Tiotropium
Aclidinium
161
Anticholinergic Agents MOA
Block M3 on bronchiolar smooth muscles and secretory tissues
162
Anticholinergic Agents Therapeutic Indications
Asthma
COPD
163
Anticholinergic Agents Adverse effects
Dry mouth
Ocular
Slow gastric emptying
tremors
164
Antimuscarinic drugs are contraindicated...
in patients with glaucoma
165
Methyl Xanthines
Theophylline
Aminophylline
Roflumilast
166
Methyl Xanthines MOA
Phosphodiesterase inhibitors cause relaxation of smooth muscle and promotes dilation
167
Methyl Xanthines Therapeutic indications
Asthma
COPD
Emphysema
168
Methyl Xanthines Adverse Effects
Nausea
Tachycardia, increase CO
increase in TPR
CNS stimulation
Insomnia
169
Roflumilast MOA
PDE4 inhibitors inhibit inflammatory cytokine and mediator release.
Inhibits neutrophil chemotaxis activity
Promotes apoptosis
170
Endothelins
Powerful vasoconstrictor produced in endothelial cells
171
Pathway of Endothelins
Prepro ET (inactive) --> Big ET (inactive) --> ET (active)
172
Enzymes in endothelins pathways
Furin-like protease
ECE-1 and ECE-2
173
Most potent vasoconstrictor in cardiovascular system
Endothelin-1
174
ET-1 and ET-2 act on
ETA and ETB
175
ET-3 acts on
ETB
176
ETA
Increases Ca+
Makes receptors more sensitive
177
ETB
Clearance receptor
Increases NO
178
Endothelin Receptor Antagonists
Bosentan
Ambrisentan
Macitentan
179
Bosentan
Dual ETA and ETB antagonist
180
Ambrisentan
Selective ETA antagonists
181
Macitentan
Selective ETA antagonists
182
Endothelin Receptor Antagonists adverse effects
Hypotension
Increased HR
Facial flushing
Edema, headaches
183
Endothelin Receptor Antagonists to treat pulmonary artery hypertension
Used in conjunction with negative inotropic agents and direct vasodilators
184
Endothelin Antagonists are contraindicated
in pregnancy
185
Groups of Prophylactic bronchodilators
Cromolyn Sodium
Leukotriene Inhibitors
186
Cromolyn Sodium
Low solubility, poorly absorbed
Must be inhaled
187
Cromolyn Sodium has no effect on
airway smooth muscle tone
188
Cromolyn Sodium is ineffective in
reversing bronchospasm
189
Cromolyn Sodium is only of value when
taken prophylactically
190
Cromolyn Sodium MOA
Alters function of delayed Cl- channels in cells
Inhibits cell activation
