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How does endothelin-1 work?
- Physiologic
- Increases intracellular Ca2+ in smooth muscle tissue of blood vessels -> contraction -> vasoconstriction.
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How does Bosentan work?
- Competitive non-selective antagonist of endothelin-1 at ET-A and ET-B receptors
- Decreased pulmonary vascular resistance.
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Name two ET-A blockers?
- Sitaxentan
- Ambrisentan: low liver toxicity, high potency.
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Where are prostacyclins synthesized, where and how do they act?
- Synthesized in endothelial cells
- Act on smooth muscle cells through G-protein, increase protein kinases -> vasodilation.
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What do prostacyclin analogs have in their name?
-prost-.
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What is the ending of PDE 5 selective inhibitors, how do they work?
- -afil
- inhibit degradation of cGMP -> vasodilation.
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What is Inomax, how are systemic effects prevented?
- Inhaled nitric oxide
- Rapid binding to hemoglobin.
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What is Dornase Alfa, what is it used for?
- Recombinant human DNase (rhDNase)
- Enzyme selectively cleaves DNA
- Inhalable, used in CF, reduces viscosity in lungs
- Improved clearance of secretions.
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What is the MOA of N-Acetyl-Cysteine (NAC)?
Rate limiting step in glutathione (GSH) synthesis - provides precursor so increases GSH (antioxidant).
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What is NAC used for?
Acetominophen overdose, decreases amount of toxic NAPQI.
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What three factors does the viscosity of mucus depend on?
- Concentration of mucoproteins
- Presence of di-sulfide bonds
- DNA.
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Mucolytics usually contain one of which two compounds?
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What is the MOA of ambroxol?
- Stimulates synthesis and release of surfactant by type 2 pneumocytes
- Also has local anaesthetic effect.
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What is almitrine, how does it work?
- Respiratory stimulant
- Agonist at peripheral chemoreceptor
- Increase PaO2 and decrease PaCO2.
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What do surfactant analogs have in their name?
-surf-.
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