{"id":4958,"date":"2025-01-15T00:36:00","date_gmt":"2025-01-15T00:36:00","guid":{"rendered":"https:\/\/www.osmosis.org\/blog\/?p=4958"},"modified":"2025-10-01T11:38:23","modified_gmt":"2025-10-01T19:38:23","slug":"usmle-step-1-question-of-the-day-epinephrine-response","status":"publish","type":"post","link":"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-epinephrine-response","title":{"rendered":"USMLE\u00ae Step 1 Question of the Day:\u00a0Epinephrine response"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_80 ez-toc-wrap-center counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">In This Article<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #999;color:#999\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #999;color:#999\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-epinephrine-response\/#The_correct_answer_to_todays_USMLE%C2%AE_Step_1_Question_is%E2%80%A6\" >The correct answer to today\u2019s USMLE\u00ae Step 1 Question is\u2026<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-epinephrine-response\/#Incorrect_Answer_Explanations\" >Incorrect Answer Explanations<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-epinephrine-response\/#Main_Explanation\" >Main Explanation<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-epinephrine-response\/#Major_Takeaway\" >Major Takeaway\u00a0<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-epinephrine-response\/#References\" >References\u00a0<\/a><\/li><\/ul><\/nav><\/div>\n\n<p class=\"wp-block-paragraph\"><strong>Let&#8217;s examine a clinical scenario involving a 73-year-old man who experiences hypotension during surgery following bowel perforation repair. Can you identify the potential mechanisms leading to his decreased response to repeated doses of epinephrine despite minimal intraoperative blood loss? Let&#8217;s find out!<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A 73-year-old man with no significant past medical history develops a bowel perforation and subsequently undergoes surgical repair. He develops significant hypotension while under general anesthesia. Intraoperative blood loss is minimal. A large dose of epinephrine is administered, which temporarily raises the patient&#8217;s blood pressure. Several subsequent doses of epinephrine are administered, causing a much weaker response. Which of the following mechanisms is likely contributing to the decreased effects of this medication?&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>A. Increased activity of intracellular arrestin proteins<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>B. Increased number of extracellular receptors<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>C. Increased production of secondary messenger molecules<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>D. Decreased breakdown of the medication<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>E. Decreased sequestration of extracellular receptors<\/strong><\/p>\n\n\n\n<p class=\"has-text-align-center wp-block-paragraph\"><em>Scroll down for the correct answer!<\/em><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"The_correct_answer_to_todays_USMLE%C2%AE_Step_1_Question_is%E2%80%A6\"><\/span>The correct answer to today\u2019s USMLE\u00ae Step 1 Question is\u2026<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>A. Increased activity of intracellular arrestin proteins<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Before we get to the Main Explanation, let\u2019s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Incorrect_Answer_Explanations\"><\/span>Incorrect Answer Explanations<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>B. Increased number of extracellular receptors<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong> If more extracellular receptors were available, there would be more binding to the agonist (medication), making it more likely to maintain or increase a cellular response (i.e., drug effect).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>C. Increased production of secondary messenger molecules<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong> Since medications\/drugs work by binding to a cellular receptor and causing effects via secondary messengers, an increase in secondary messengers is more likely to maintain or increase a cellular response (i.e. drug effect).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>D. Decreased breakdown of the medication<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong> Since more medication would be available, this is unlikely to lead to decreased effect.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>E. Decreased sequestration of extracellular receptors<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong> Decreased sequestration of receptors to bind the medication would result in more receptors available for drug binding and thus more intracellular changes (i.e., effect) from the medication.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Main_Explanation\"><\/span>Main Explanation<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><span style=\"margin: 0px;padding: 0px\"><strong>Desensitization and tolerance<\/strong>&nbsp;are important concepts in pharmacodynamics and refer to a decreased effect of a drug (e.g., alcohol, heroin) or medication over time following subsequent doses.<\/span> Over time, as an agonist binds to its cellular receptor, it may lose its ability to produce a robust response within cells via secondary messengers. Desensitization (also called tachyphylaxis) generally occurs rapidly and can occur after the first dose of a medication. On the other hand, tolerance occurs always after repeated doses and may take weeks or months. In this patient, he is likely experiencing desensitization (tachyphylaxis) to epinephrine, so repeated doses exert a weaker effect than the original dose.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Desensitization and tolerance can occur via many mechanisms, with several of the most common mechanisms outlined below:&nbsp;<\/p>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li><strong>Downregulation of receptor expression.<\/strong> For example, chronic opioid use results in downregulating the number of receptors available to bind the opioid or may increase the degradation or sequestration of receptors. This results in stronger doses of opioids needed to produce the same effect.&nbsp;&nbsp;<\/li>\n<\/ol>\n\n\n\n<ol start=\"2\" class=\"wp-block-list\">\n<li><strong>Uncoupling of receptors to secondary messengers.<\/strong> This is often mediated by proteins called <strong>arrestins<\/strong>, which bind to G-protein-coupled receptors to prevent interaction with secondary messengers. They can also tag these receptors for endocytosis. <strong>This is common in desensitization (tachyphylaxis).<\/strong>&nbsp;<\/li>\n<\/ol>\n\n\n\n<ol start=\"3\" class=\"wp-block-list\">\n<li><strong>Exhaustion of intracellular intermediary molecules.<\/strong> This can occur with drugs such as amphetamines, which eventually lead to the depletion of secondary messengers within cells.&nbsp;&nbsp;<\/li>\n<\/ol>\n\n\n\n<ol start=\"4\" class=\"wp-block-list\">\n<li><strong>Increased breakdown of agonists.<\/strong> For example, this can occur with chronic alcohol use, as \u201ctolerance\u201d increases with repeated chronic use due to more rapid degradation of ethanol.&nbsp;<\/li>\n<\/ol>\n\n\n\n<ol start=\"5\" class=\"wp-block-list\">\n<li><strong>Physiologic adaptation in the body.<\/strong> For example, this can occur with thiazide diuretics due to increased activity of the renin-angiotensin-aldosterone system.&nbsp;<\/li>\n<\/ol>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Major_Takeaway\"><\/span>Major Takeaway\u00a0<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Desensitization (tachyphylaxis) and tolerance can occur via several cellular mechanisms, and both lead to a decreased effect of an agonist (drug or medication) over time. Desensitization generally occurs after a few doses (can occur after the first dose), whereas tolerance takes weeks to months.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"References\"><\/span>References\u00a0<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Katzung &amp; Trevor\u2019s Pharmacology Examination and Board Review, 12th Edition. McGraw-Hill Education\/Medical (2018)&nbsp;<\/li>\n\n\n\n<li>Rang and Dale\u2019s Pharmacology. Elsevier (2019)&nbsp;<\/li>\n\n\n\n<li>Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches. International Journal of Molecular Sciences (2017).&nbsp;<\/li>\n\n\n\n<li>GPCR desensitization: Acute and prolonged phases. Cellular Signaling (2018)&nbsp;<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image aligncenter size-full\"><a href=\"https:\/\/www.osmosis.org\/plans\/md\"><img loading=\"lazy\" decoding=\"async\" width=\"700\" height=\"250\" src=\"https:\/\/hm-healthdigital-multisite.go-vip.net\/osmosisblog\/wp-content\/uploads\/sites\/2\/2024\/10\/Blog_Display_Ads_MOBILE3_2023.png\" alt=\"\" class=\"wp-image-4729\" srcset=\"https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/10\/Blog_Display_Ads_MOBILE3_2023.png 700w, https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/10\/Blog_Display_Ads_MOBILE3_2023.png?resize=300,107 300w\" sizes=\"auto, (max-width: 700px) 100vw, 700px\" \/><\/a><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\"><em><strong>Want more &nbsp;USMLE\u00ae Step 1 practice questions?&nbsp;Try Osmosis by Elsevier today! Access your&nbsp;<a href=\"https:\/\/www.osmosis.org\/login?type=create\" target=\"_blank\" rel=\"noreferrer noopener\">free trial<\/a>&nbsp;and discover why millions of current and future clinicians and caregivers love learning with us.<\/strong><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Examine a clinical case of a 73-year-old man with hypotension during surgery and learn about the pharmacological mechanisms, including desensitization, affecting his response to epinephrine. Enhance your understanding of managing intraoperative hypotension effectively.<\/p>\n","protected":false},"author":202,"featured_media":4959,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_feature_clip_id":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_post_was_ever_published":false},"categories":[27,20,16,1366,1369,44],"tags":[319,302,318,317,84,308,149,320,261,316],"class_list":["post-4958","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine","category-exam-prep","category-do","category-questions","category-step-1-questions","category-step-1","tag-anesthesiology","tag-clinical-case-study","tag-epinephrine","tag-hypotension","tag-medical-education","tag-medical-students","tag-patient-care","tag-pharmacodynamics","tag-pharmacology","tag-surgery"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>USMLE\u00ae Step 1 Question of the Day:\u00a0Epinephrine response - Osmosis Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-epinephrine-response\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"USMLE\u00ae Step 1 Question of the Day:\u00a0Epinephrine response - Osmosis Blog\" \/>\n<meta property=\"og:description\" content=\"Examine a clinical case of a 73-year-old man with hypotension during surgery and learn about the pharmacological mechanisms, including desensitization, affecting his response to epinephrine. 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