LABA drugs have been shown to have a side effect of increasing the risk of sudde

Question

LABA drugs have been shown to have a side effect of increasing the risk of sudden death to an uncontrollable asthma attack (http://annals.org/aim/article/724674/meta-analysis-effect-long-acting-agonists-servere-asthma-exacerbations-asthma). This is thought to occur through non-responsiveness to emergency inhaler medication during an acute asthma attack resulting from chronic LABA use. What could best explain this? Beta-1 adrenergic receptor upregulation Beta-1 adrenergic receptor downregulation Alpha-1 adrenergic receptor downregulation Beta-2 adrenergic receptor downregulation Beta-2 adrenergic receptor upregulation

Explanation / Answer

LABA( long acting beta agonist) has effect on Beta 2 adrenergic receptor and coupled to a stimulatory G protein of adenylyl cyclase. This enzyme produces the second messenger cyclic adenosine monophosphate (cAMP). In the lung, cAMP decreases calcium concentrations within cells and activates protein kinase A. Both of these changes , inactivate myosin light-chain kinase and activate myosin light-chain phosphatase. In addition, 2 agonists open large conductance calcium-activated potassium channels and thereby tend to hyperpolarize airway smooth muscle cells. The combination of decreased intracellular calcium, increased membrane potassium conductance, and decreased myosin light chain kinase activity leads to smooth muscle relaxation and bronchodilation.

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