Respiratory Flashcards
Describe innervation of the lungs
SNS from thoracic ganglia innervate smooth muscles of bronchi an pulmonary blood vessels, bronchodilation via B2
PSNS innvervation via the VAGUS nerve and M3 (muscarinic receptor) both cause bronchoconstriction, M3 increases mucus secretion too
Non-adrenergic non-cholinergic (NANC) nerves relax airway smooth muscle by releasing ___ and _____
Nitric oxide and vasoactive intestinal peptide
List histologic mediators of bronchoconstriction (in asthma)
Eosinophils, mast cells, neutrophils, macrophages, basophils, T lymphocytes
Other probable mediators include cytokines, interleukin 3,4,5, arachidonic acid metabolites of leukotrienes and prostaglandins, histamine, adenosine, platelet activating factor
Do steroids work better for asthmatics or COPD?
Asthmatics, it helps with inflamed, edematous, hypersensitive airways
Almost never used for COPD
Which is reversible/irreversible between asthma and COPD?
Asthma airflow obstruction is reversible, using albuterol and steroids
COPD is irreversible
In asthma, inhaled corticosteroids help reduce frequency of exacerbation, bronchodilators help with breathlessness
Step 1-5 treating airway outflow disorders?
1: short-acting bronchodilators
2: regular inhaled corticosteroid
3: long-acting bronchodilators
4: phosphodiesterase inhibitors, methylanthines, leukotriene inhibitor
5: oral corticosteroid
Other: cromolyns
List short-acting and long-acting B-adrenergic agonists that are selective to B2
Short-acting: terbutaline, albuterol, levalbuterol, salbutamol, metaproterenol-alupent, bitolterol
Long-acting: salmeterol
B-adrenergic agonist MOA?
G proteins activate adenyl cyclase which increases the production of cAMP leading to bronchodilation, dec Ca increases K conductance
Primarily bronchodilates, also inhibits mediator release from mast cells and increases mucus clearance using cilia
B-adrenergic agonist onset, DOA?
Rapid onset of 15-30 min
Short DOA 30-60 min (albuterol up to 4 hours)
B-adrenergic agonist side effects?
Tremor
Inc HR
Vasodilation
Hyperglycemia, hypokalemia, hypomagnesemia
What are the isomers of albuterol selective to? R-albuterol and S-albuterol
S-albuterol: beta1
R-albuterol: beta2
What is terbutaline used for? Dose for adults and children? Route?
Status asthmaticus, also for preterm labor
Child: subq 0.01mg/kg
Adult: subq 0.25 mg q 15 min
Subq dose resembles response of epi
What are salmeterol and formoterol used for?
Long-acting B-agonist used for prevention, NOT for acute flare-up or surgery
They are long-acting due to lipophillic side chains that resist degradation
Duration 12-24 hours
Muscarinic receptor antagonist (anticholinergics) MOA?
Competivive antagonists at the muscarinic acetylcholine receptors
Antagonizing Ach results in broncho-relaxation and decreased mucus secrtion
Airway smooth muscle extends as far distal as ____
Terminal bronchioles
Which muscarinic receptor is the most important subtype in lung because it mediates smooth muscle relaxation (bronchodilation) and decreases mucus gland secretion?
M3
Muscarinic receptor antagonist (anticholinergics) uses?
Treats COPD (especially chronic bronchitis to help with secretions) Secondary line of treatment for asthma in patients resistant to beta agonist or significant cardiac disease
Atropine: what class of drug is it? Side effects?
A muscarinic receptor antagonist/ anticholinergic/ bronchodilator
Administered 1-2 mg diluted in 3-5 mL of saline via nebulizer
Highly absorbed across respiratory epithelium
Side effects: tachycardia, nausea, dry mouth, GI upset
How does ipratropium bromide compare to atropine?
Derivative of atropine
Not significantly absorbed compared to atropine
More dry mouth and GI upset, less tachycardia
How does tiotropium compare to atropine?
Long acting anticholinergic
Not significantly absorbed across respiratory epithelium which results in few side effects
Methylxanthines/ Phosphodiesterase inhibitor MOA? Uses? Examples?
MOA: nonspecific inhibition of phosphodiesterase isoenzymes (3,4) which prevents cAMP degradation in airway smooth muscle as well as in inflammatory cells resulting in airway relaxation and bronchodilation
Uses: COPD and asthma
Theophylline and aminophylline
Theophylline therapeutic plasma level?
NARROW
10-20 mg/mL
Methylxanthine/PDI metabolism excretion?
Metabolized in the liver
CP450 INDUCER so interacts with CP450 inhibitors (such as cimetidine and antifungals)
Excreted by the kidney
Methylxanthine/PDI side effects?
Many side effects due to multiple MOAs Arrythmias, hypotension N/V Irritability, insomnia, seizures, brain damaged Hyperglycemia, hypokalemia
Inhaled corticosteroids: MOA, use?
MOA: alter genetic transcription by increasing transcription of genes for B2 receptors and anti-inflammatory proteins, decrease transcription of genes for pro-inflammatory proteins. Indirect inhibition of mast cells, reverse asthma features. Dec vascular permeability, dec airway edema, dec airway hyper-responsiveness
Uses of inhaled corticosteroids? Name some inhaled corticosteroids.
Uses: preventative treatment for asthma patients (supportive therapy, not a cure), MOST IMPORTANT in managing asthma, also it prolongs the response of beta-agonists
Beclomethasone, triamcinolone, fluticasone, budesonide
____% of inhaled corticosteroids reaches the airway
25%
80-90% of the inhaled dose reaches oropharynx and is swallowed (unless mouth is rinsed after using inhaler)
Systemic effects are decreased through inhalation
Inhaled corticosteroid side effects?
Osteopenia/osteoporosis Delayed growth in children Oropharyngeal candidiasis Hoarseness Hyperglycemia, then hypokalemia
Cromolyn MOA?
Inhibits antigen-induced release of histamine and inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, and leukotrienes from pulmonary mast cells
Inhibits allergic response to an antigen except one that has been activated
Cromolyn side effects?
Rare but bad Laryngeal edema Angioedema Urticaria Anaphlyaxis
Cromolyn use?
Prophylactic therapy of bronchial asthma, does NOT relieve allergic response
Leukotriene inhibitors: MOA, use, name a couple?
Inhibits leukotriene pathway (leukotrienes are synthesized from arachidonic acid when inflammatory cells are activated)
Used for bronchial asthma but NOT effective in acute asthma attacks
Zileuton, Montelukast (singulair)
Name two types of asthma drugs that you would NOT use in an acute asthma attack?
Cromolyn
Leukotriene inhibitors
Zileuton key points? MOA?
Lipoxygenase inhibitor that blocks biosynthesis of leukotrienes from arachidonic acid
Long-term improvement of PFT and asthma symptoms
Low bioavailability, low potency, hepatotoxic, not widely use
Montelukast (singulair)
Leukotriene receptor antagonist that blocks bronchoconstriction and smooth muscle effects
Improves bronchial tone, pulmonary function, asthma symptoms
Cysteinyl-leuktriene 1 receptor is what it blocks
Caution with warfarin, will prolong PT
Name an Anti-IgE antibody, what is it used for?
Omalizumab
Binds to IgE and decreases quantity of IgE and prevents IgE binding to mast cells to mitigate acute response of inhaled allergen
Down-regulates IgE receptors to reduce stimulation of T2 lymphocytes
