Test 3 - Asthma and Bronchodilators (10/14 & 10/16) Flashcards
factors affecting ventilation
- airway resistance
Airway diameter
-contraction and relaxation of smooth muscle
-ANS input
where is the greatest resistance in the airway
medium bronchi
Why do smokers cough in the mornings?
bc the cilia is damaged so they cough to try to get the shit up
Obstructive airway disorders lead to ______
hyper-reactive airway.
Obstructive disorders discussed in class
- asthma
- chronic bronchitis
- emphysema
- COPD
what is the most common chronic disease in children?
obstructive disorders (asthma)
what is the histamine challenge?
spray a little histamine into airway and checking forced expiratory volume.
normal people will have a drop.
asthmatics will have a significant drop.
why are asthma cases increasing?
Suspects.
1. second hand smoke
2. worsening air quality
3. hygiene hypothesis
what is the hygiene hypothesis. how can we counteract this?
we all wanted to be clean and wash our hands so our immune system doesn’t react to pathogens like normal. starts to react to our own autoantigens.
according to Dr T. get a dog.
Symptoms of asthma
- Wheezing
- Breathlessness
- chest tightness
- coughing (more at night)
what is asthma? what cells are involved
airway inflammation - obstruction.
WBC, epithelial cells
describe the smooth muscle walls in an asthmatic pt.
even in relaxed state they are inflamed and thickened
Air trapping in alveoli can lead to _____
emphysema
In asthma we have increased responsiveness of _____ and ____ to various stimuli
trachea; bronchi
What causes the widespread narrowing of airways in asthma? (3)
- contraction of airway smooth muscle
- mucosal thickening
- mucous plugs formed and thicken
symptoms of Croup. what can cause it. what can we give?
following viral infection. Seal like barking cough. nebulized epi
symptoms of COPD
chronic bronchitis + emphysema.
chronic productive cough that lasts for at least 3 months of the year and for at least 2 consecutive years
Symptoms of bronchitis
Inflammation of bronchioles
Alveolar walls in emphysema
Permanent enlargement of alveolar walls. loss of elasticity
What is FEV1 checking for? how is it done? what will we see in asthma pts?
Bronchial hyperreactivity test.
Inhaling increasing concentrations of histamine or methacholine and then forced expiration volume over 1 second.
significant fall in forced expiratory volume
what is PEF?
Peak expiratory flow
-maximum flow of forced expiration
(asthma treatment) what will we give for contraction of smooth muscle. what will we give for edema and cellular infiltration.
- beta adrenergic agonists (beta 2 specific)
- anti-inflammatory agents
what types of asthma are there?
Intrinsic - genetic factors
Atopic (extrinsic) - type 1 hypersensitivity reactions
What happens during a second time we are introduced to an allergin?
the b memory cells will recall the allergen and Mast cells degranulate and produce histamines
What happens during the first exposure to an allergen?
- breath in allergen
- dendritic cells (antigen presenting cell) - process and break up allergen and present it on the surface with MHC2 receptor and migrates to the closest lymph node
- MHC2 receptor is presented to a T Cell - T cell releases interleukin 4 which activates B cells
- B cells activated and produce antibodies/
- B cells turn into plasma cells (antibody producing factories) and B memory cells (will cause significant reaction the next time allergen is encountered)
- IgE will bind to surface of mast cells
- Mast cells become sensitized once IgE sticks to them
What is dupixent? who is it used for?
Blocks interleukin 4 from binding to the B cell. used for asthma and allergy
Early mediators are responsible for the early reaction. They diffuse through the cell wall and cause what?
muscular contraction and vascular leakage and immediate bronchoconstriction
What is a slower mediator that is released from mast cells (after histamine) in early stages of asthma and the effect
- Leukotrienes: bronchospasm. Enhances histamine effects
- Prostaglandins D2: Proinflammatory. Potent bronchconstricting agent
Both are GPCR
What is the immediate mediator that is released following an allergy response? What does it cause?
Histamine.
Induces smooth muscle contraction and bronchospasms
The eosinophil and neutrophil release a number of different substances called
Proteases.
They break down proteins holding cells together and they can infiltrate into smooth muscle and cause contraction.
but this causes swelling of the tissues because now its leaky
What draws in the eosinophil and the neutrophil?
The release of cytokines from T cells
what role does mucus have?
defense against irritants and microorganisms
Mucus is produced by ____
goblet and epithelial cells
What happens to the mucus viscosity in asthma?
it is increased
What is the sympathetic effect on airway diameter?
relaxes bronchiolar smooth muscle (B2 receptor)
What is the parasympathetic effect on airway diameter?
Contracts bronchiolar smooth muscle ( M3 receptor).
How is our normal resting tone of airway smooth muscle maintained?
Parasympathetic, vagus nerve
In the CNS the vagal afferent is responsible for what?
Sensory. inhaled irritant
In the CNS the efferent vagus is responsible for what?
Release ACh. bind to M3. will constrict the smooth muscle in the airway
in sympathetic response we get more of an effect from ____
circulating catecholamines (epi).
Do we get help from alpha blockers during an asthma attack?
no, the major resistance airways have alpha adrenergic receptors. activation produces bronchoconstriction. so we want beta 2 to relax
What can cause an asthma attack
- allergens
- respiratory infections
- irritants
- certain meds
- exercise
- GERD
- anxiety/stress/scared
What are the 2 categories for treatment for reactive airway diseases.
Short term relievers (sympathomimetics)
long-term controllers (corticosteroids)
when do we use a short term reliever vs a long term controller?
Short term- during an asthma attack
long term- to prevent an asthma attack
What are the 3 sub categories for the short term bronchodilators for asthma?
-beta agonists (specifically 2)
-anti muscarinic
-methylxanthines
What are the 2 subcategories for long term anti-inflammatory agents for asthma
-steroids
-antibodies
what are the two mechanisms for the leukotriene antagonists for the long term treatment of asthma?
-Inhibit 5 Lipoxygenase
-inhibit receptor binding
Short term asthma treatment: Sympathomimetics.
beta agonists have what affect?
relax airway smooth muscle.
-inhibit substance from mast cells
-increases mucociliary transport
Sympathomimetics toxic effects
skeletal muscle tremor
Terbutaline, albuterol, metaproterenol, pirbuterol and salmeterol are examples of what?
Beta 2 agonists (bronchodilators)
Epinephrine for asthma. What receptor? what is the effect?
affects beta 1 and 2.
-bronchodilation (B2)
-tachycardia, arrythmias, worsening of angina (B1)
epi can stimulate alpha adrenergic receptors and cause what
constriction of arterioles and decreased laryngeal edema
isoproterenol in asthma
potent bronchodilator. strictly beta
its a sympathomimetic
SABA and LABA
short acting beta agonist
long acting beta agonist
Primary short acting beta 2 agonist for asthma?
Albuterol
beta 2 selective drug used for asthma. what does it cause?
albuterol.
bronchodilation.
Terbutaline (IV)
Salmeterol and formoterol for asthma, what receptor? action?
Long acting beta 2 agonist. duration 12 hours.
sympathomimetic agents are usually delivered via _____ because it has _____
oral inhalation. greatest airway effects.
when we use oral inhalation how much medication do we actually get?
10-20%
Methylxanthines: theophylline, theobromine, caffeine. what affect do these have for asthma? why aren’t they that great?
what is the main one?
Inhibit phosphodiesterase. slight anti inflammatory.
not that great bc they are non medicines. coffee, tea and chocolate
Theophylline
How does theoohylline work?
PDE inhibitor. breaks down cAMP.
decrease bronchial tone
Ipratroprium bromide is a muscarinic antagonist used for what? how does it work
COPD. decrease in bronchial tone
Atropine is a muscarinic antagonist used for ____.
COPD
What methylxanthine is used for COPD? what is a special consideration?
Purified theophylline. have to monitor for toxicity for purified version (the med itself, not the tea)
Atropine, ipratropium bromide and tiotropium are what kind of meds and what are they used to treat? Short acting or long acting?
Short term relievers. Muscarinic antagonist (anticolinominetic). COPD
Why would we use ipratropium bromide over atropine for COPD
its more selective for the lungs and longer acting.
Tiotropium is most useful for what? what kind of med is it?
COPD. muscarinic antagonist
Corticosteroids are used for ______ and it has an ________ effect. Are these short term or long term?
Asthma
anti-inflammatory
long term
what type of corticosteroids do we like to use primarily?
Inhaled
True/False: COPD is less responsive to corticosteroids
True
Steroids are ____ soluble
lipid
where are glucocorticoids produced?
adrenal cortex
Glucocorticoids inhibit immune response by _____
blocking transcription/translation
Where is the receptor for the corticosteroid?
in the cytoplasm
What happens after the corticosteroid binds to the receptor?
migrates into the nucleus itself where it selectively binds to different genes with GRE (glucocorticoid response elements). Will only bind to genes that have the GRE.
The GRE (glucocorticoid response element) can be a _____ or a _____.
Silencer (shut down production of genes) or enhancer (increase production of genes)
What will happen when the corticosteroid binds to the GRE?
Increase in annexin-1
Increase in secretory leukoprotease inhibitor
Increase in IL-10
Inhibit NFkB
What effect does an increase in annexin-1 have?
it will suppress phospholipase A2.
suppresses overall pathway for inflammation
what effect does an increase in secretory leukoprotease inhibitors have?
blocks protease enzymes that are produced by WBC from a secondary allergen response
What effect does an increase in IL-10 have following glucocorticoid administration?
its an immunosuppressive cytokine. anti inflammatory
what effect would we see from a decrease in NFkB following glucocorticoid administration?
repressing the pro inflammatory cytokine
What are the negatives to corticosteroids
-increase osteoporosis with long term
-slow the rate of growth in children
-orophanyngeal candidiasis (inhaled)
what are the positives for corticosteroids?
-reduce bronchial activity
-increases airway caliber
-reduce frequency of asthmatic exacerbations
-improve quality of life
What is the most effective route of administration for corticosteroids?
Aerosol
Long term use of corticosteroids (inhaled)
-reduces symptoms
-improves pulmonary function
-reduces need for oral steroids
-reduces bronchial reactivity
How do Anti-IgE monoclonal antibodies work? short term or long term?
Long term. target IgE that binds to mast cells and keep them from degranulating.
Xolair would be an example of what? how is it used (short term/long term)
Anti-IgE monoclonal antibody. long term controller
Leukotriene pathways inhibitors work by what?
interrupting synthesis pathway.
How can leukotriene pathway inhibitors interrupt synthesis pathway?
- inhibit 5-lipoxygensase
- inhibit binding to receptor
Montelukast is a leukotriene pathway inhibitor. How does it work?
inhibits binding to the receptor.
In a secondary response, leukotriene’s cause what?
- bronchoconstriction
- increase bronchial reactivity
- mucosal edema
- mucus hypersecretion
Clinical pharmacology for mild asthma
beta 2 agonists PRN (rescue inhaler)
Clinical pharm for mod asthma (nocturnal symptoms)
Anti-inflammatory
-inhaled corticosteroids
-oral leukotriene receptor antagonist
For frequent symptoms as asthma what would we use?
inhaled corticosteroids
Clinical pharm for severe symptoms or airway obstruction
-oral corticosteroids
-switch to inhaled (over time)
-anti-IgE antibody
What are the 5 steps for asthma progression
- symptoms <2X/month
- symptoms >2X/month (not daily)
- symptoms most days
- symptoms most days + low lung function
- uncontrolled symptoms
For step 1 asthma what is the short term reliever and long term controller
Short- Short acting beta 2 agonist (SAB2A)
Long- Low dose inhaled corticosteroid
For step 2 asthma what is the short term reliever and long term controller
Short: short acting B2 agonist (SAB2A)
Long: low dose ICS, formoterol. Alt: leukotriene receptor antagonist
For step 3 asthma what is the short term reliever and long term controller
Short: ICS/formoterol
long: Low dose ICS-LABA, leukotriene receptor antagonist
For step 4 asthma what is the short term reliever and long term controller
Short: ICS/formoterol
Long: medium dose ICS-LABA add tiotropium or leukotriene receptor antagonist
For step 5 asthma what is the short term reliever and long term controller
Short: ICS/formoterol
Long: High dose ICS-LABA, oral corticosteroids (short course), refer to specialist, add tiotropium, anti-IgE mab
For COPD we want to use meds that do what? what is the standard treatment?
Give us a more prolonged opening of the airway.
Long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)
What drug/class of meds are used for both asthma and COPD?
What are the Drug/class used in asthma?
Which ones are used for COPD
COPD meds are often ____
Combination of different drugs.
Ex. Trelegy has
-Fluticasone (anti-inflammatory)
-anticholinergic
-beta 2 agonist (rol)
Severe acute attacks
-oxygen
-frequent or continuous inhalation of beta-2 agonist
-systemic steroids (prednisone)
-Intubate
