Exam 1 Respiratory Flashcards
Airway smooth muscle extends to
distal terminal bronchioles
Airway smooth muscles are influence by
PSNS and SNS
Thoracic ganglia of the SNS innervate
smooth muscles of bronchi and pulmonary blood vessels
tracheobronchial blood vessels and glands
Sympathetic tone is
bronchodilation via beta 2 receptors
Vagus nerve of the PSNS system innervates
smooth muscles of bronchi
Beta adrenergic receptors located in the
smooth muscle of the blood vessels, skin muscle mesentary and bronchial smooth muscle
B2 adrenoreceptors cause
widening of airways (bronchodilation)
increase intracellular cyclic AMP
Nonadrenergic non-cholinergic nerves (NANC)
influences on inflammation and smooth muscle tone
M3
mediate bronchoconstriction via the activation of IP3 which increases the intracellular Ca2+ concentrations
Asthma causes recurrent episodes of
wheezing breathlessness chest tightness cough (night and early am) tachypnea prolonged expiration phase of respiration fatigue
Asthma is
a chronic inflammatory disorder of the airways characterized by increase responsiveness of the tracheobronchial tree to a variety of stimuli
Asthma creates airways that are
inflammed, edematous
bronchial hypersensitivity/reactivity to irritant stimuli
difficult with air outflow
Degree of airway hyper-responsiveness and bronchoconstriction parallels
the extent of inflammation
Asthma is characterized by
inflammation
hyperreactivity
reversible airway obstruction
airway hyper-responsiveness and inflammation from allergen in bronchial mucosa leads to
activation of T2 lyphmocytes and cytokine release
Asthma medications are aimed
at flattening the response to the mediators
Asthma mediators
eosinophils mast cells neutrophils macrophages basophils T lymphocytes
Probably mediators of acute bronchoconstriction
cytokines, interleukins
arachiddonic acid metabolites, leukotrienes and prostraglandins
histamine, adenosine and platelet activating factor
Atopic Extrinisic asthama
produced by an allergen and IgE synthesis
COPD Factors
genes smoking age/gender lung growth/development exposure to particles: cigarette smoke, occupational dust and fumes, indoor air pollution socioeconomic status asthma/bronchial hyperactivity chronic bronchitis infections
Neutrophils/marcophages
COPD
Esinophils/ mast cells
asthma
COPD/Emphysema/Bronchitis
cell death of destruction of the alveoli, thickening of membrane air gas exchange over inflated alveoli
Obstruction is either
not reversible or incompletely reversible by bronchodilators
Cell death is caused by
desctruction of alveoli due to lung parenchyma, degraded matrix and toxic actions of inflammatory cells
COPD
results in enlargement of air spaces, fibrosis, and increase mucous production
Steroids have
limited effect on inflammation process
Inhaled corticosteroids help
reduce frequency of excerbations
Bronchodilators in COPD
best for patients with chronic breathlessness “worsened by exertion”
Steps of Airway Outflow Disorders
step 1: short acting bronchodilators step 2: regular inhaled corticosteroids step 3: long acting bronchodilators step 4: PDE inhibitors, methyxanthines, leukotriene inhbitor Step 5: oral corticosteroid other- cromolyns
Bronchdilators
B2 agonist
anticholinergics
methylxanthines
Receptor selectivity to B2 is ____ more times more strongly than B1
200-400
Short acting Beta agonist
terbutaline, albuterol, levalbuterol, salbutamol
Long acting beta agonist
salmeterol
MOA of Beta Agonist
Coupled to stimluatory G proteins
activate adenlyl cyclase which increases the production of cAMP which leads to bronchodilation, reduced Ca release and alters membrane conductance
inhibits mediator release from mast cells
increases mucous clearance by action of the cilia
Pharmacokinetics of B adrenergic agonist
rapid onset of action (within minutes) short DOA (4-6 hours) good for use as a rescue inhaler given: inhalation/aerosol powder or nebulized orally or injected (SC) short or long acting
Side effects of Beta Adrenegic agonist
minimized by inhalation delivery tremor increased HR vasodilation metabolic changes (hypok, hyperg, hypomagnesmia)
Albuterol
preferred selective beta 2 agonist
Albuterol Dose
100mcg/puff
2 puff 4-6hrs
nebulizer 2.5-5mg in 5ml of saline
DOA of albuterol
4 hours with some relief evident up to 8 hours
R albuterol has more affinity
to beta 2
S albuterol more affinity
to beta 1
Albuterol has _____ effects with volatile anesthetics on bronchomotor tone
addictive
Side effects of Albuterol
tachycardia, hypokalemia
Anesthetic use of Albuterol
4 puffs blunt airway response to tracheal intubation in asthmatic patients
Metaproterenol-alupent
beta 2 agonist for treatment of asthma
administered via metered dose
not to exceed 16 puff/day
Pirbuterol-Maxair
beta two agonist
2 puffs (400mcg) via metered dose
not to exceed 12 inhalations/day
Terbutaline
administered SC,oral, inhalation
treats asthma
SC administration resembles epi response
Terbutaline SC dose for children
0.01mg/kg
Terbutaline SC dose for adult
0.25mg q15 min
Terbutaline Metered dose inhaler is and each dose is
16-20puff/day
200mcgs
Long acting B agonist examples
salmeterol
combination with fluticasone
formoterol
Long acting B agonist
have liphophic side chains that resist degradtion
duration 12-24 hours
good for prevention not flare up
MOA of bronchodilators/anticholinergics
competitive antagonist at muscarinic acetylcholine receptors
Uses of bronchodilators/anticholinergics
treatment of COPD
secondary line of treatment for asthma in patients resistant to beta agonist or significant cardiac disease
Examples of Bronchodilators/Anticholinergics
atropine
ipratropium bromide
tiotropium
Atropine
naturally occuring alkaloid
highly absorbed across respiratory epithelium
causes systemic anticholinergic effects (tachycardia, dry mouth, nausea, Gi upset)
How is atropine dosed
1-2 mg diluted in 3-5 ml sof saline via nebulizer
Ipratropium bromide
quaternary ammonium salt derivative of atropine
antagonizes endongenous ach at m3
Dose of Ipratropium bromide
40-80mcg via metered dose in 2-4 puffs via nebulizer
DOA and onset of Ipratropium bromide
slow onset 30 minutes
DOA 4-6 hours
Compared to atropine, Ipratropium bromide is ____
not siginicantly absorbed
S/E of Ipratropium bromide
inadvertent oral absorption
dry mouth and GI upset
Tiotropium
quaternary ammonium salt
long acting anticholinergic
not significantly absorbed across resp epithelium= few side effects
approved by FDA for COPD
COPD medications
tiotropium
Ipratropium bromide
atropine
Examples of Methylxanthines- Phosphodiesterase Inhibitors
Theophylline, Aminophylline
MOA of Methylxanthines
nonspecific inhibition of phosphodieterase isoenzymes (types 3 and 4) which prevent cAMP degradtion in airway smooth muscle as well as in inflammatory cells
PDIs have multiple MOAs and are nonselective they have
various side effects and have a narrow TI
theophylline
therapeutic plasma level of 10-20mcg/ml
toxic at >20mcg/ml
Susceptile to drug to drug interactions due to metabolism by CYP 450 (cimetidine and antifungals ie CYP 450 inhibitors)… increase level of drug
metabolized in liver excreted in kidney
What drug do you have to caution with halothene?
theophylline
Side Effects of PDI
headache N/V irritability/restlessness insomnia cardiac arrthymias seizures SJS
Anti-Inflammatory agents
inhaled corticosteroids
cromolyns
leukotriene inhibitors
anti- IgE antibodies
Examples of Inhaled corticosteroids
beclomethasone
triamcinolone
fluticasone
budensonide
Pre-op Considerations with inhalated corticosteroids
may consider use of corticosteroid administration 1-2 hours preop
they prolong the response of beta agonist
may consider 5 day course of combined corticosteroid and albuterol to minimize the risk of intubation evoked bronchospasm
Inhaled corticosteroids
reduce the number of inflammatory cells in the airways and the damage to airway epithelium
vascular permeability is reduced which decreases airway edema
overall reduction in airway hyper-sensitivity
inhaled corticosteroids are considered the most
important drug in management of asthma
major preventative treatment for patients with asthma
MOA of Inhaled Corticosteroids
alters gene transcription
increases transcription of genes for beta 2 receptor and anti-inflammatory proteins
decreases transcription of genes for pro-inflammatory proteins
induce apoptosis in inflammatory cells (esinophils, TH2, lymphocytes)
indirect inhibition of mast cells over time
reverses many ft of asthma
used as suppressive therapy not a cure
Side Effects of Corticosteroids
oropharyngeal candidiasis osteopenia/osteoporosis delayed growth in children hoarseness hyperglycemia
Cromolyn
stabilizes mast cells
MOA of Cromolyn
inhibits antigen-induced release of histamine
including release of inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, and leukotrienes form pulm mast cells
inhibits allergic response to antigen but not the allergic response once it has been activated
Administration of Cromolyn
inhalation 8-10% enters the systemic circulation
take 4x daily
How much inhaled dose reaches oropharynx is swallow of inhaled corticosteroids
80-90%
How much inhaled corticosteroid reaches airway
25%
Principle use of cromolyn
prophlaytic therapy of bronchial asthma
Cromolyn does not
relieve allergic response after initiation
not a rescue inhaler
S/e of cromolyn are
laryngeal edema
angioedema
uticaria
anaphylaxis
Leukotriene Inhibitors
synthesized from arachidonic acid when inflammatory cells are activatd
not effective in the treatment of acute asthma attacks
few extrapulmonary effects
Leukotriene Inhibitor examples
zileuton
montelukast
Zileuton
lipoxygenase inhibitor which blocks the biosynthesis of leukotrienes from arachiondic acid
produces bronchodilation, improves asthma symptoms and has shown long term improvements in PFTs
low bioavailability, low potency and significant adverse effects
hepatotoxic
no widely used
Montelukast-singulair
leukotriene receptor antagonist block the mechanism of bronchoconstriction and smooth muscle effects
blocks the ability of leukotrienes to bind to cysteinyl-leukotriene 1 receptor
improve bronchial tone, pulm function, and asthma symptoms
Montelukast-singulair with warfin
can result in prolonged PT
Omalizumab
monoclonal antibody derived from DNA
given in the early and late phase of asthmatic response
given SC 2-4 parenterally infused
high cost and incovenience
binds to igE (decrease IgE circulating quantity and prevent IgE from binding to mast cell)
down regulation of receptors
adverse effet: triggering of immune response
