NBME 21 Enhanced action of the agonist at β-adrenergic receptors (NBME Answers)

NBME 21 Answers

nbme21/Block 2/Question#39 (reveal difficulty score)
A 64-year-old man with bronchospastic ...
Enhanced action of the agonist at β-adrenergic receptors 🔍 / 📺 / 🌳 / 📖
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submitted by ∗wasabilateral(47)

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This is what I thought but not sure if it’s correct. There is a UWorld q where it describes co-administration of cortisol and epinephrine. Cortisol significantly enhances the effect of epi because cortisol has a permissive effect on maintaining the adrenergic receptors.

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194orbust per UWorld, "cortisol exerts a permissive effect on many hormones to help improve the response to a variety of stressors. For example, cortisol increases vascular and bronchial smooth muscle reactivity to catecholamines". FA also uses the effect of cortisol on catecholamine responsiveness as the lone example for a permissive drug interaction (FA2018 pg 229). The difference here is that we're talking about exogenous glucocorticoid and adrenergic agonist. I guess it was expected for us to assume that the mechanism is analogous for the analogous drugs +16

maxillarythirdmolar I'm sure it's related to the activating effect of Cortisol on phenylethanolamine-N-methyltransferase, converting NE to Epi. Sounds like a synergistic thing to me. (FA.83) +4

feeeeeever My logic is probably flawed, but I also thought that if cortisol has the ability inhibit COX, LOX, and NFKB you can reduce inflammation and bronchoconstrictive mediators. Therefore, the B2 agonists would have a greater effect since things like LTB4 will be reduced. +2

feeeeeever *LTC4, LTD4, LTE4 for bronchoconstriction, my bad +1

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submitted by 5thgencephalosporin(8)

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“The combination of a long-acting beta 2 agonist (LABA) and an inhaled corticosteroid is more efficacious in asthma and [COPD] than [...] either alone. Corticosteroids may regulate beta 2 receptor function by increasing expression of the receptor, restoring G-protein/beta 2 receptor coupling, and inhibiting beta 2 receptor downregulation.”

https://www.ncbi.nlm.nih.gov/pubmed/16113435

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sahusema In short, cortisol upregulates adrenergic receptors and makes them more sensitive +

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submitted by ∗adong(144)

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FA19 p.233 cortisol has a permissive effect on catecholamines

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submitted by ∗sam1(22)

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This seems to be a relevant paper: https://www.ncbi.nlm.nih.gov/pubmed/11897997

"These data indicate that glucocorticoids only transiently enhance beta(2)AR gene transcription and fail to increase steady-state levels of beta(2)AR protein in human airway epithelial cells. Nonetheless, glucocorticoid-induced effects on the beta(2)AR-AC system of human airway epithelial cells contribute to the beneficial effects of corticosteroids in asthma by enhancing the functional response to beta(2)-agonists."

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submitted by ∗maxillarythirdmolar(45)

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I'm sure it's related to the activating effect of Cortisol on phenylethanolamine-N-methyltransferase, converting NE to Epi. Sounds like a synergistic thing to me. (FA.83)

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alexv0815 this was my thought too +

kevin It's permissive because without cortisol Epi wouldn't be able to attain its full effect +

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submitted by ∗an_improved_me(91)

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I feel the wording is god-awful.

It makes it sound like cortisol increases the interaction between a given beta-agonist and its receptor. In reality, it increases the number of receptors, without changing the interaction between them. For me, this was an elimination of everything else, and choosing the least terrible answer.

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