Respiratory agents Flashcards
Airway smooth muscle is under the influence of
PSNS (bronchoconstriction) and SNS (Bronchodilation)
SNS fibers cause _____ through
bronchodilation via beta 2 receptors
PSNS innervation causes ____ through____
bronchoconstriction via muscarinic M3 receptors (also M1)
causes increased secretions
innervation is via the vagus nerve
Beta 2 adrenoreceptors cause
widening of the airways (Bronchodilation) via increased intracellular cyclic AMP which decreases Calcium binding
Stimulation of____ leads to bronchoconstriction
Vagus nerve (PSNS)
M3 receptors are found on the
bronchial smooth muscle & they cause bronchoconstriction by increasing intracellular Ca2+ concentrations
also cause mucus secretion
Pulmonary obstructive diseases
asthma & COPD
Describe asthma
reversible airflow obstruction disease
chronic inflammatory disorder of the airways characterized by increased responsiveness of the tracheobronchial tree
Asthma s/s
wheezing, breathlessness, chest tightness, cough, tachypnea, prolonged expiration phase of respiration, fatigue
asthma is characterized by
inflammation, hyper-reactivity & reversible airway obstruction
Asthma mediators include
eosinophils, mast cells, cytokines, interleukins, leukotrienes, & histamine
Medications for asthma are aimed at
flattening the response to mediators
COPD is characterized by
cell death & destruction of the alveoli
results in enlargement of air spaces, fibrosis, and increased mucus production
non-reversible
COPD therapy differs from asthma because
steroids have limited effect on inflammation process in COPD
inhaled corticosteroids help in reducing frequency of exacerbations
Steps of treatment for airway outflow disorders:
step 1: short-acting bronchodilators step 2: regular inhaled corticosteroid step 3: long-acting bronchodilators step 4: phosphodiesterase inhibitors, methylxanthines, or leukotriene inhibitors Step 5: oral corticosteroid other- cromolyns
Bronchodilators include
Beta-adrenergic agonists, anticholinergics, methylxanthines
Examples of beta adrenergic nonspecific drugs include
Epinephrine (beta 1, beta 2, and alpha)
Isoproterenol- (beta 1 & beta 2)
Metaproterenol (beta 1 & beta 2)
Examples of short-acting beta2 selective adrenergic drugs include
terbutaline, albuterol, levalbuterol (used mostly in OR since it is more B2 specific), and salbutamol
Examples of long-acting beta 2 selective adrenergic drugs include
salmeterol
Beta 2 adrenergic selective receptors are
200-400 times more strongly bound to beta 2 than beta 1
Mechanism of action of beta adrenergic agonists
attach to G proteins–> activates adenlyl cyclase which INCREASES production of cAMP–>bronchodilation
reduced intracellular calcium release & alters membrane conductance
primary effect is to DILATE the BRONCHI via direct action on beta 2 adrenoreceptors
By direct action on the beta 2 adrenoreceptors, beta 2 adrenergic agonists
result in smooth muscle relaxation & bronchodilation, inhibit mediator release from mast cells, and increase mucus clearance by action on the cilia
What is the onset of action and duration of action for bronchodilators?
onset: within minutes
duration of action: 4 to 6 hours
used as rescue inhalers for this reason
Beta adrenergic agonists are typically used as
rescue inhalers
Beta adrenergic agonists are given via
inhalation or aerosol, powder or nebulized, orally or injected (SC)
What are the side effects of beta 2 adrenergic agonists?
tremor, increased heart rate, vasodilation, metabolic changes (hyperglycemia, hypokalemia & hypomagnesemia)
minimized by inhalation delivery
Albuterol (drug class & duration of action)
is a preferred selective beta 2 agonists & duration of action is 4-8 hours
Albuterol is administered via
metered dose- 100 mcg/puff
2 puffs q4-6 hours
nebulizer 2.5-5.0 mg in 5 mL of saline
Albuterol has an additive effect
with volatile anesthetics on bronchomotor tone
There are 2 isomers of albuterol:
R-albuterol levalbuterol has more affinity for beta 2
S-albuterol has more affinity for beta 1 (more side effects)
Side effects of albuterol include
tachycardia, hypokalemia, anesthesia use: 4 puffs blunt AW responses to tracheal intubation in asthmatic patients
Do not use ____ in patients with reactive airways
desflurane
Metaproterernol-Alupent (drug class & administration)
beta 2 agonists for tx of asthma
administered via metered dose
not to exceed 16 puffs/day
Prbuterol-Maxair (drug class & administration)
Beta 2 agonists
2 puffs (400 mcg) via metered dose
not to exceed 12 inhalations/day
Terbutaline (drug class & administration)
beta 2 agonist
administered oral, SC, inhalation
SC administration resembles the response of epi
Terbutaline dosages
SC dose for child: 0.01 mg/kg
Adult SC dose is 0.25 mg q15 min
Metered dose inhaler 16-20 puffs/day
Each dose is 200 mcgs
Long acting beta agonists include
Salmeterol (combination drug-fluticasone & salmeterol)
formoterol
Long-acting beta agonists (chemical structure & duration of action)
have a liphophilic side chain that resist degradation
duration in 12-24 hours
Good for prevention NOT for acute flare-up
Long-acting beta agonists can be used for
prevention NOT acute flare-up
The mechanism of action for muscarinic receptor antagonists is
competitive antagonists at muscarinic acetylcholine receptors
muscarinic 1 & 3 subtype are the targets
By antagonizing endogenous Ach–> broncho-relaxation & decreased mucus secretion
Muscarinic receptor antagonists are used for
treatment of COPD
SECONDARY LINE for asthma in patients resistant to beta agonist or significant cardiac disease
Examples of muscarinic receptors antagonists include
atropine, ipratropium bromide, and tiotropium
Atropine administration
formally used for tx of asthma
administered 1-2 mg diluted in 3 to 5 ml of saline via nebulizer
Atropine signs and symptoms
highly absorbed across respiratory epithelium which causes systemic anticholinergic effects including: tachycardia, nausea, dry mouth, and GI upset
Tiotropium (structure & drug type)
quaternary ammonium salt
LONG acting anticholinergic
Tiotropium is used for ____ & side effects include
approved for COPD & not significantly absorbed across respiratory epithelium which results in few side effects
Ipratropium bromide structure & MOA
quaternary ammonium salt derivative of atropine
antagonizes the effect of endogenous acetylcholine at M3 receptor subtypes
not significantly absorbed compared to atropine
What is the onset & duration of action of ipratropium bromide?
Onset: 30 minutes
Duration of action: 4 to 6 hours
Administration of ipratropium bromide
metered dose inhaler 40-80 mcg in 2-4 puffs via neb
inadvertent oral administration leads to dry mouth and GI upset
The mechanism of action of methylxanthines-phosphodiesterase inhibitors is
nonspecific inhibition of phosphodiesterase isoenzymes which prevents cAMP degradation and inflammatory cells–> airway relaxation & bronchodilation
Examples of methylxanthines-phosphodiesterase inhibitors include
theophylline, aminophylline
Methylxanthines-phosphodiesterase inhibitors uses
COPD & asthma (more historically used b/c of many side effects & need to monitor blood levels)
Side effects of methylxanthines phosphodiesterase inhibitors include
headache, nausea/vomiting, irritability/restlessness, insomnia, cardiac arrhythmias, seizures, Stevens Johnson syndrome
How is methylxanthine-phosphodiesterase inhibitors metabolized and excreted?
metabolized- liver
excreted-kidney
susceptible to drug-drug interactions d/t metabolism by CYP450 (cimetidine & antifungals which are CYP-450 inhibitors)
Theophylline concerns
caution with halothane b/c sensitizes myocardium
& toxicity
therapeutic plasma level of 10-20mcg/ml
toxic >20 mcg/ml
Anti-inflammatory agents include
Inhaled corticosteroids, cromolyns, leukotriene inhibitors, anti-IgE antibodies
Anti-inflammatory agents work to
flatten response to mediators that cause inflammation
Inhaled corticosteroids are used
- ***as major preventive treatment for patients with asthma
* ***used as suppressive therapy, NOT A CURE
The mechanism of action of inhaled corticosteroids is
alters genetic transcription
Increases transcription of genes for beta 2 receptor and anti-inflammatory proteins
decreases transcription of genes for pro-inflammatory proteins
induces apoptosis in inflammatory cells
indirect inhibition of mast cells over time
What is considered the most important drug in management of asthma?
inhaled corticosteroids
Inhaled corticosteroids work to
reduce the # of inflammatory cells in the airways & damage to airway epithelium
vascular permeability is reduced which decreases airway edema
overall reduction in airway hyper-responsiveness
Inhaled corticosteroid drugs include
beclomethasone
triamcinolone
fluticasone
budesonide
Inhaled corticosteroids administration considerations:
may consider the use of corticosteroid administration 1-2 hours pre-op
prolong the response of beta agonists
may consider 5 day course of combined corticosteroid and albuterol to minimize the risk of intubation evoked bronchospasm
Side effects of inhaled corticosteroids include
oropharyngeal candidiasis, osteopenia/osteoporosis, delayed growth in children, hoarseness, hyperglycemia
systemic effects are decreased thru inhalation
(rinse mouth after inhaler)
With inhaled corticosteroids,
25% of inhaled corticosteroids reach the airway
80-90% of the inhaled dose reaches oropharynx and is swallowed
The mechanism of action of cromolyn drugs
stabilize mast cells
MOA: inhibits antigen-induced release of histamine
including the release of inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, and leukotrienes from pulmonary mast cells
inhibits immediate allergic response to antigen but not the allergic response once it has been activated
Cromolyn is administered via
inhalation w/ 8-10% entering the systemic circulation
taken 4 times daily
must be used for 7 days to see effect
Cromolyn is NOT
used as a rescue inhaler
Side effects of cromolyn include
infrequent: urticaria, anaphylaxis, angioedema, and laryngeal edema
The principle use of cromolyn is
prophylactic therapy of bronchial asthma
does not relieve an allergic response after initiation
Leukotriene inhibitors are used for
bronchial asthma
NOT effective in the tx of ACUTE asthma attacks Zi
Drug prototypes of leukotriene inhibitors include
Zileuton & montelukast
Zileuton works by
blocks the biosynthesis of leukotrienes from arachidonic acid
produces bronchodilation, improves asthma symptoms, and has shown long-term improvement in PFT
Zileuton is not widely used because
it has low bioavailability, low potency, and significant adverse effects including hepatotoxic & hepatitis
Montekulast-Singulair works by
block the mechanism of bronchoconstriction and smooth muscle effects
leukotriene receptor antagonists
blocks the ability of leukotrienes to bind to cysteinyl-leukotriene 1 receptor
Montelukast-Singulair is caution with
co-administration with warfarin which can result in prolonged PT
Montekulast is used to
improve bronchial tone, pulmonary function, and asthma symptoms
Anti-IgE antibodies are used for patients with
asthma
Anti-IgE antibodies work by
removal of IgE antibodies from circulation mitigate the acute response of the inhaled allergen
____ is an example of an anti-IgE antibody
Omalizumab
Omalizumab is a (admin)
monoclonal antibody derived from DNA
given in the early & late phase of asthmatic response
given SQ for 2-4 weeks/parenterally infused
High cost & inconvenience
Omalizumab works by
binds to IgE- decreases quantity of circulating IgE & prevents binding of IgE to mast cells
also causes down-regulation of receptors
An adverse effect of omalizumab is
rare: triggering of an immune response
Drugs that are used for bronchodilation include:
B2 adrenergic agonists (cAMP production–> bronchodilation), anticholinergics (competitive inhibitor of cholinergic), methylxanthines/PDE inhibitors (inhibit breakdown of cAMP)
Drugs that are used for inflammation and mucous include:
steroids- decrease mucosal edema
cromolyn- mast cell stabilization
