Pharm 2: Asthma
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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
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
Irritant stimulation of sensory afferents can lead to release of ____.
Release of Substance P
Substance P causes:
- Smooth muscle contraction
- Mucous release
- Local inflammatory response-vasodilation
Mast cells and eosinophils cause what, during an asthma attack?
Bronchoconstriction, mucus release
Beta Adrenoreceptor Agonists
- Mainstay of therapy
- B2 selective compounds are primarily used
- Nonselective Epi use in emergencies
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
Which class of asthma-treating-drugs reduces inflammation and sensitivity of airway smooth muscle to stimulation?
What is your goal for inhaled steroids?
Lowest does that maintains good control
What is your goal for systemic (oral, injection) steroids?
Minimize both dose and duration
Which asthma-treatment drugs upregulate B-adrenergic receptors?
Name the inhaled steroids?
Beclomethasone, Budesonide, Flunisolide, Fluticasone, Mometasone, Triamcinolone
Which asthma-treatment drugs can cause oral candidiasis?
Inhaled steroids (due to immunosuppression of oral cavity)
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
Which drugs treat asthma by inhibiting the action of leukotrienes?
Recombinant humanized antibody against the Cε3 domain of IgE?
How does it work?
- Complexes IgE preventing activation of mast cells and basophils
- Use only have primary tx has failed
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)
One side effect of PDE inhibitors is that they strengthen ____
skeletal muscle contraction (improves ventilation due to increased strength of diaphragm)
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)
Muscarinic Antagonists are used for early inhalation therapy. Which one is not used?
Atropine is not used (it has too many side effects).
Main Muscarinic Antagonists given for asthma?
- Ipratropium (I pray I can breathe again)
- Tiotropium- long acting (24 hr)
Uncontrolled asthma= activity how often?
3 or more times/ week
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)
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