Pharm - Asthma Drugs Flashcards
Parasympathetic nerves control what 2 structures in lungs?
Bronchial smooth muscle, mucosal glands
Mucosal cells have what type of muscarinic receptors?
M1, M3
Bronchial SM has what type of muscarinic receptors?
M2, M3
Besides bronchial SM, where else can M2 receptors be found? What is their purpose here?
M2 receptors can be found at pre ganglionic nerve terminal, inhibit release of Ach into synapse of neuromuscular junction
Besides muscarinic receptor at parasympathetic pre ganglionic nerve terminal, what other receptor is present? What is released from it?
Nicotinic receptors, release Ach
The only receptor (if you block it) at presynaptic ganglion terminal that blocks ganglionic signal (blocks the release of Ach from the nerve terminal) is?
nicotinic receptor
In asthma exacerbation, what neurotransmitter is released via post ganglionic parasympathetic nerves, worsening the asthma?
Ach released into NMJ, worsening bronchoconstriction
In asthma, what does the accumulation of eosinophils at the parasympathetic post ganglionic synapse cause?
Eosinophil accumulation will inhibit M2 receptors at NMJ, allowing Ach to be released, worsening the asthma exacerbation
Sympathetic innervation of lung primarily along what? What receptors here?
blood vessels, alpha 1,2, beta2
Adrenergic receptor density highest in what part of lungs?
bronchioles
Muscarinic receptor density highest in what part of lungs?
Trachea, upper airways
Which is more effects, B2 agonists or muscarinic antagonists? Why
B2 agonists, because of location of B2 receptors. They are in the bronchioles vs muscarinic receptors being in the trachea and upper airways.
Norepi stimulates what receptors?
alpha 1, alpha 2, beta 1
Beta 2 receptors can only be stimulated by what adrenergic neurotransmitter?
Epinephrine. not norepi
Nonspecific beta agonists?
- Epinephrine
- Ephedrine
- Isoproterenol
B2 specific, quick onset-short acting drugs?
- Albuterol
- Xopenex (Levalbuterol)
- Terbutaline
B2 specific, slow onset- long acting drugs?
- Salmeterol
- Salmeterol + Fluticasone (Advair)
- Formoterol
- Formoterol + Budesonide (Symbicort)
- Formoterol +Mometasone
Sympathomimetics relation with cAMP?
B2 agonists increase rate of cAMP synthesis, which causes bronchodilation
B2 agonists increase cAMP levels via what mechanism
stimulate adenylyl cyclase to increase production of cAMP
MOA of Theophylline
B2 agonist. PDE-inhibitor, prevents breakdown of cAMP to AMP, allowing increased cAMP levels = bronchodilation
Adenosine and Acetylcholine on bronchial tone?
bronchoconstriction
Major adverse effect of beta agonists?
hypokalemia- QT prolongation = fatal arrhythmias (be careful with drugs causing hypokalemia like Loop/Thiazide Diuretics)
Antimuscarinic drugs?
Atropine
Ipratropium
Tiotropium
Umeclidinium
MOA of antimuscarinics?
Compete with acetylcholine for muscarinic receptor binding
Adverse effect of antimuscarinics?
Contact with medication and touching eye can cause pupillary dilation and cycloplegia
What is the mechanism of Cromolyn?
Inhibit mast cell degranulation, inhibit the inflammatory response, reduces bronchial hyperactivity
Mechanism of action of Glucocorticoids?
combines with GRa in the cytosol–> inhibits NF-kB–>inhibits transcription of inflammatory genes
What effect do glucocorticoids have on Th2 cells?
Competes with GATA-3 for translocation to the nucleus to prevent transcription of IL-4, IL-5, and IL-13
ADE of glucocorticoids?
oral candidiasis, decreased bone density in premenopausal women, decreased growth rate of children, glucose intolerance, increase blood pressure/weight, immunosuppresion
What is Lipocortin? What is the effect of glucocorticoids on it?
It suppresses phospholipase a2, glucocorticoids up regulate transcription of Lipocortin–> decrease inflammation
What is Cushingoid Syndrome?
Cushing like syndrome seen in chronic glucocorticoid therapy, especially in children; Weight gain, moon face, buffalo hump, acanthosis
Which has more of a role in acute bronchoconstriction, Leukotrienes of histamine?
Leukotrienes are 1000x more potent
What are the 2 LTD4 receptor antagonists?
Zafirlukast and Monteleukast
What kind of asthma CAN leukotriene modifiers be fairly effective in?
ASA induced asthma
Name the Leukotriene synthesis blocker
Zileuton
What does Zileuton do?
Inhibit syntehsis of LTB4, C4, D4, E4; Decreases smooth muscle contraction and blood vessel permeability, reduced leukocyte migration to the affected area
Main ADE of Zileuton?
Causes elevation of hepatic enzymes–> Check LFTs
What is the IgE monoclonal antibody?
Omalizumab
Efficacy of Bupropion in treatment of COPD?
Anti-depressant that helps to block nicotinic receptors
Possible role of Theophylline in COPD therapy?
Theophylline recruits histone deacetylase II–> inhibits transcription of inflammatory genes–> less damage to lung parenchyma
Beta agonists effective in early, late, or both phases of an asthma attack?
Early phase (bronchoconstriction); don’t really play a role in the late phase (inflammatory)
