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What is the parasympathetic receptor on airway smooth muscle?
What is it's neurotransmitter?
- M3 is the receptor
- ACh is the neurotransmitter
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Do bronchial smooth muscles have sympathetic innervation?
What do they have instead?
Epinephrine released from what activates them?
- No direct sympathetic innervation.
- B2 receptors are present and they are activated by Epi secreted from the adrenal medulla
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Irritant stimulation of sensory afferents can lead to release of ____.
Release of Substance P
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Substance P causes:
- Smooth muscle contraction
- Mucous release
- Local inflammatory response-vasodilation
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Mast cells and eosinophils cause what, during an asthma attack?
Bronchoconstriction, mucus release
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Beta Adrenoreceptor Agonists
- Mainstay of therapy
- B2 selective compounds are primarily used
- Nonselective Epi use in emergencies
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1) Name 7 B2 Selective Agonists
2) Which ones can be given orally?
3) Which one is given subcutaneously?
4) Name the two long acting ones.
- 1) Albuterol, terbutaline, metaproterenol, bitolterol, pirbuterol, salmeterol, formoterol
- 2) Albuterol, terbutaline, metaproterenol
- 3) Terbutaline
- 4) Salmeterol, formoterol
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Which class of asthma-treating-drugs reduces inflammation and sensitivity of airway smooth muscle to stimulation?
Steroids
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What is your goal for inhaled steroids?
Lowest does that maintains good control
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What is your goal for systemic (oral, injection) steroids?
Minimize both dose and duration
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Which asthma-treatment drugs upregulate B-adrenergic receptors?
Corticosteroids
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Name the inhaled steroids?
Beclomethasone, Budesonide, Flunisolide, Fluticasone, Mometasone, Triamcinolone
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Which asthma-treatment drugs can cause oral candidiasis?
Inhaled steroids (due to immunosuppression of oral cavity)
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Inhibition of leukotriene formation (5-lipooxygenase inhibitor) also treats asthma. Which drug inhibits leukotriene formation? This also increase the lifetime of what?
- Zileuton inhibits leukotriene formation.
- Increases the lifetime of theophylline and drugs metabolized by CYP3A4
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Which drugs treat asthma by inhibiting the action of leukotrienes?
Zafirlukast, Montelukast
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Recombinant humanized antibody against the Cε3 domain of IgE?
How does it work?
- Omalizumab
- Complexes IgE preventing activation of mast cells and basophils
- Use only have primary tx has failed
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Phosphodiesterase inhibitors inhibit breakdown of ____ by inhibiting _____.
Other examples include?
- cAMP, PDE (cAMP produced by B2-adrenoceptor activation initiates a phosphorylation cascade causing relaxation of airway smooth muscle)
- Adenosine receptor antagonist, Methlxanthine (caffeine/theophylline)
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One side effect of PDE inhibitors is that they strengthen ____
skeletal muscle contraction (improves ventilation due to increased strength of diaphragm)
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Cromolyn/Nedocromil mechanism of action?
- Nebulizer- Inhibit mast cell degranulation by inhibiting chloride channels in the mast cell membranes.
- Prophylactic (doesn't do anything to histamine that's already been released)
- Strengthen skeletal muscle contraction (diaphragm)
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Muscarinic Antagonists are used for early inhalation therapy. Which one is not used?
Atropine is not used (it has too many side effects).
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Main Muscarinic Antagonists given for asthma?
- Ipratropium (I pray I can breathe again)
- Tiotropium- long acting (24 hr)
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Uncontrolled asthma= activity how often?
3 or more times/ week
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Name the 4 main therapies for Asthma
- Removal of Ag or other stimuli
- Smooth muscle relaxants (B2-selective, methyl xanthines- theophyline, Muscarinic Antagonists)
- Reduction of inflammation: (Inhibit mast cell degranulation- Cromolyn, Nedocromil; Leukotriene Inhibitors- 5 LOX inhibitor, Leukotriene receptor antagonists; Steroids)
- Anti-IgE
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