Respiratory Agents Flashcards
Is asthma an obstructive disease or a restrictive disease?
Obstructive disease - problem with outflow
which obstructive disease is reversible?
Asthma
What is the airway smooth muscle influenced by?
PSNS and SNS
What does the SNS cause in the airway smooth muscle?
Bronchodilation
What does the PSNS cause in the airway smooth muscle?
Bronchoconstriction
Which receptors cause bronchodilation?
beta 2 receptors
PSNS innervation is via the ____
vagus nerve
Which receptors cause bronchoconstriction?
muscarinic (M3) receptors
Beta 2 receptors causes
smooth muscle relaxation in blood vessels, bronchi, uterus, and bladder, bronchodilation, increased intracellular cAMP
NonAdrenergic NonCholinergic Nerves (NANC)
influences on inflammation and smooth muscle tone
Stimulation of the vagus nerve leads to?
bronchoconstriction
How does M3 receptors mediate bronchoconstriction?
via the activation of IP3 which increases the intracellular Ca++ concentrations
also mediates mucus secretion
Asthma description
chronic inflammatory disorder of the airways characterized by increase responsiveness of the tracheobronchial tree to a variety of stimuli
Asthma recurrent symptoms
wheezing, breathlessness, chest tightness, cough, tachypnea, prolonged expiration phase, fatigue
Main goal of therapy for treating asthma
decrease stimulus (flatten the response to mediators)
asthma creates airways that are
inflamed, edematous airways, bronchial hypersensitivity, reactivity to irritant stimuli, difficulty with outflow
asthma hyperresponsiveness and inflammation from allergen leads to
activation of T2 lymphocytes and cytokine release
bronchospasm
lower in the bronchus/in the lungs
treat with gas (sevo or iso)
laryngospasm
glottic closure
break with 3-5mg rocuronium
Mediators involved in asthma
eosinophils and mast cells mostly
other probable mediators - cytokines, interleukins, leukotrienes, histamine
What kinds of things can cause/lead to COPD?
genes, smoking, age/gender, lung growth/development, exposure to particles, socioeconomic status, asthma, chronic bronchitis, infections
COPD description
cell death and destruction of the alveoli due to impaired lung parenchyma, degraded matrix, and toxic actions of inflammatory cells that leads to enlargement of air spaces, fibrosis, and increased mucus production
Steroids have limited effect on inflammation in ___
COPD
Which type of treatments are used in airway outflow disorders?
short acting bronchodilators, regular inhaled corticosteroid, long acting bronchodilators, phosphodiesterase inhibitors, methylxanthines, leuokotriene inhibitors, oral corticosteroids, cromolyns
Example of bronchodilators
beta adrenergic agonists, anticholinergics, methylxanthines
Short acting beta agonists
terbutaline, albuterol, levalbuterol, salbutamol
Which short acting beta agonist is B2 selective?
levalbuterol
what is an example of a long acting beta agonist
salmeterol
MOA of beta agonists
GPCRs, activate adenlyl cyclase which increases the production of cAMP and decreases intracellular Ca++ release which leads to bronchodilation directly on beta 2 receptors
Onset of action, DOA, route of administration of beta agonists
Onset - rapid, within minutes
DOA - short, 4-6 hours
Route - inhalation, aerosol, powder or nebulized, orally, SQ
Side effects of beta agonists
minimized by inhalation delivery, tremor, increased HR, vasodilation, hyperglycemia, hypokalemia, hypomagnesemia
Albuterol dosing
inhaler 100 mcg/puff; 2 puffs q 4-6hours
nebulizer 2.5-5 mg in 5mL of saline
Albuterol effect with volatile anesthetics
additive effect on bronchomotor tone
Albuterol side effects
tachycardia, hypokalemia, blunt airway responses to tracheal intubation
Which volatile agent should be avoided in asthmatics?
Desflurane
Dosing considerations for Metaproterenol-Alupent
not to exceed 16 puffs/day
administered via a metered dose
Dosing considerations for Pirbuterol-Maxair
2 puffs (400 mcg) via metered dose not to exceed 12 inhalations/day
Terbutaline dosing and route administration(s)
oral, SQ, inhalation SQ = response of epi Child SQ dose = 0.01 mg/kg Adult SQ dose = 0.25 mg q 15 minutes inhaler = 16-20 puffs/day (200 mcgs per dose)
Long acting beta agonists
have a lipophilic side chain that resists degradation
duration 12-24 hours
good for prevention
Anticholinergics MOA
competitive antagonist at muscarinic acetylcholine receptors
by antagonizing endogenous ACh leads to
bronchorelaxation, decreased mucus secretion
what are anticholingeric used for?
treatment of COPD, secondary treatment of asthma that are resistant to beta agonist or significant cardiac disease
should asthma patients be on long acting beta agonists?
not unless they’re on a corticosteroid otherwise high risk of death
atropine
1-2mg diluted in 3-5 mL of saline via neb
highly absorbed and can cause systemic effects including tachycardia, nausea, dry mouth, GI upsest
ipratropium bromide
antagonizes the effect of endogenous acetylcholine at M3 receptors
ipratropium bromide dosing
inhaler 40-80 mcg in 2-4 puffs
slow onset 30 minutes
DOA 4-6 hours
Methylxanthines- Phosphodiesterase Inhibitors MOA
nonspecific inhibition of phosphodiesterase isoenzymes which prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells that leads to airway relaxation and bronchodilation
What is something you want to monitor with someone taking theophylline?
blood levels
has narrow therapeutic index
therapeutic level 10-20mcg/mL
toxic level >20 mcg/mL
Which inhalational agent should you take caution using with theophylline?
halothane
Which bronchodilator is contraindicated with drugs metabolized by the CYP450 system?
theophylline
side effects of methylxanthines- PIs
HA, N/V, irritability, insomnia, cardiac arrhythmias, seizures, stevens johnson syndrome
inhaled corticosteroids MOA
major preventive treatment for asthma
alter genetic transcription
reduce the number of inflammatory cells in the airways and the damage to airway epithelium
which drug class is considered the most important in managing asthma?
inhaled corticosteroids
Anesthesia considerations for inhaled corticosteroids
give 1-2 hours preop, prolongs the response of beta agonists, may have 5 day course of combined corticosteroid and albuterol to minimize the risk of intubation evoked bronchospasm
side effects of corticosteroids
oropharyngela candidiasis, osteopenia/osteoporosis, delayed growth, hoarseness, hyperglycemia
Cromolyn MOA
stabilize mast cells
inhibits antigen-induced release of histamine and immediate allergic response to an antigen
administered via inhalation 4x/day
Cromolyn side effects
infrequent but serious!
laryngeal edema, angioedema, urticaria, anaphylaxis
leukotriene inhibitors MOA
inhibit leuokotriene pathways which are synthesized by arachidonic acid when inflammatory cells are activated
Examples of leukotriene inhibitors
zileuton and montelukast
zileuton MOA and why it isn’t widely used
blocks biosynthesis of leukotrienes from arachidonic acid leading to bronchodilation and improves asthma symptoms
not widely used because it is hepatotoxic and can cause hepatitis
montelukast-singulair MOA and which drug to use with caution
block the mechanism of bronchoconstriction and smooth muscle effects improving bronchial tone, pulmonary function, and asthma symptoms
use caution with warfarin because it can prolong the PT
Omalizumab
anti-IgE monoclonal antibody derived from DNA that is given in the early and late phase of asthmatic response
decreases quantity of IgE and prevents binding to mast cells
very expensive and inconvenient
last ditch effort
