Editing Beta blocker (section)

=== β-Adrenergic receptor antagonism ===

Stimulation of β<sub>1</sub> receptors by epinephrine and norepinephrine induces a positive [[chronotropic]] and [[inotropic]] effect on the heart and increases cardiac conduction velocity and automaticity.<ref>{{cite book | vauthors = Michel MC, Insel PA | chapter = Adrenergic Receptors in Clinical Medicine |title= The Adrenergic Receptors in the 21st Century | veditors = Perez DM |year= 2006 |publisher= Humana Press |isbn= 978-1-58829-423-4 |page= 135 | chapter-url= https://books.google.com/books?id=QNpIsKwp8PUC&q=%CE%B21+receptors+positive+chronotropic+inotropic+effect&pg=PA135 |access-date= 2010-09-08 }}{{Dead link|date=October 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Stimulation of β<sub>1</sub> receptors on the kidney causes [[renin]] release.<ref>{{cite book |title=Harrison's Nephrology and Acid-Base Disorders | vauthors = Jameson JL, Loscalzo J |year=2010 |publisher=McGraw-Hill Companies |isbn=978-0-07-166339-7 |page= 215 |url=https://books.google.com/books?id=zVQZpJnQM_AC&q=%CE%B21+receptors+kidneys+renin&pg=PA215 |access-date=2010-09-08}}</ref> Stimulation of β<sub>2</sub> receptors induces [[smooth muscle]] relaxation,<ref>{{cite book | vauthors = Lewis KP, Gonzalez RM, Balonov K | chapter = Vasoactive Amines and Inotropic Agents |title= Surgical Intensive Care Medicine| veditors = O'Donnell JM, Nácul FE |year= 2009 |publisher= Springer |isbn= 978-0-387-77892-1 |page= 47 | chapter-url= https://books.google.com/books?id=Bih5AXq_0uMC&q=b2+receptors+smooth+muscle+relaxation&pg=PA47 |access-date= 2010-09-08}}</ref> induces tremor in [[skeletal muscle]],<ref name="pmid1968452">{{cite journal | vauthors = Ahrens RC | title = Skeletal muscle tremor and the influence of adrenergic drugs | journal = The Journal of Asthma | volume = 27 | issue = 1 | pages = 11–20 | year = 1990 | pmid = 1968452 | doi = 10.3109/02770909009073289 }}</ref> and increases [[glycogenolysis]] in the [[liver]] and [[skeletal muscle]].<ref>{{cite book |title=Sport and exercise pharmacology | vauthors = Reents S |year=2000 |publisher=Human Kinetics |isbn=978-0-87322-937-1 |page= 19|url=https://books.google.com/books?id=8ysOZlGnkC0C&q=beta+blocker+stimulation+glycogenolysis&pg=PA19 |access-date=2010-09-10}}</ref> Stimulation of β<sub>3</sub> receptors induces [[lipolysis]].<ref>{{cite book |title=Anatomy and Physiology | vauthors = Martini FH |year= 2005 |publisher= Pearson Education |isbn=978-0-8053-5947-3 |page=394 |url=https://books.google.com/books?id=0e08PrEMQJoC&q=beta+3+stimulating+lipolysis&pg=PA394 |access-date= 2010-09-10}}</ref>

Beta blockers inhibit these normal epinephrine- and norepinephrine-mediated [[sympathetic nervous system|sympathetic]] actions,<ref name="Frishman_2005" /> but have minimal effect on resting subjects.{{citation needed|date=September 2010}}
That is, they reduce the effect of excitement or physical exertion on heart rate and force of contraction,<ref>{{cite book | chapter = Beta-Blockers |title=Encyclopedia of Heart Diseases | vauthors = Khan MI |year=2006 |publisher=Elsevier |isbn=978-0-12-406061-6 |page=160 | chapter-url=https://books.google.com/books?id=xco9aJ_Y9XIC&q=beta+blockers+effects+on+heart+rate&pg=PA160 |access-date= 2010-09-10}}</ref> and also tremor,<ref>{{cite book |title=Improving Oral Health for the Elderly: An Interdisciplinary Approach | veditors = Lamster IB, Northridge ME |editor2-link=Mary Northridge | name-list-style = vanc  |year=2008 |publisher= Springer|location=New York |isbn=978-0-387-74337-0 |page= 87|url=https://books.google.com/books?id=qs2v9Sm-dVoC&q=beta+blockers+reduce+tremor&pg=PA87 |access-date=2010-10-23}}</ref> and breakdown of glycogen. Beta blockers can have a constricting effect on the bronchi of the lungs, possibly worsening or causing asthma symptoms.<ref>{{cite book | chapter = Beta Antagonist (Blocker) Medications | vauthors = Rothfeld GS, Romaine DS |title= The Encyclopedia of Men's Health | chapter-url = https://books.google.com/books?id=AyPacn1o4nIC&q=beta+blockers+opening+of+bronchi&pg=PA48  |access-date= 2010-10-23 |year= 2005 |publisher= Amaranth |isbn= 978-0-8160-5177-9  |page=48}}</ref>

Since β<sub>2</sub> adrenergic receptors can cause vascular smooth muscle dilation, beta blockers may cause some vasoconstriction. However, this effect tends to be small because the activity of β<sub>2</sub> receptors is overshadowed by the more dominant vasoconstricting α<sub>1</sub> receptors. By far the greatest effect of beta blockers remains in the heart. Newer, third-generation beta blockers can cause vasodilation through blockade of alpha-adrenergic receptors.<ref>{{cite book |title=100 Questions and Answers about Hypertension | vauthors = Manger WM, Gifford RW |year=2001 |publisher=Blackwell Science |isbn=978-0-632-04481-8 |page= [https://archive.org/details/100questionsansw0000mang/page/106 106]|url=https://archive.org/details/100questionsansw0000mang |url-access=registration |quote=beta blockers dilation of blood vessels. |access-date=2010-09-10}}</ref>

Accordingly, nonselective beta blockers are expected to have antihypertensive effects.<ref>{{cite book | chapter = Hypertension: Epidemiology, Pathophysiology, Diagnosis and Treatment | vauthors = Hurst J | veditors = Schlant RC | title= Hurst's the Heart| chapter-url= https://books.google.com/books?id=eWQAJDrVV7gC&q=beta+blockers+antihypertensive&pg=PA1564|access-date= 2010-10-07|volume= 2|year= 1997|publisher= Blackwell Science. |isbn= 978-0-07-912951-2|page=1564}}</ref> The primary antihypertensive mechanism of beta blockers is unclear, but may involve reduction in cardiac output (due to negative chronotropic and inotropic effects).<ref>{{cite book | vauthors = Reid JL |title= Lecture notes on clinical pharmacology|url= https://books.google.com/books?id=dsEmlotDt2wC&q=beta+blockers+antihypertensive+effect+reduction+of+cardiac+output&pg=PA76|access-date= 2011-03-11|volume= 6|year= 2001|publisher= Blackwell Science. |isbn= 978-0-632-05077-2|page=76}}</ref> It may also be due to reduction in renin release from the kidneys, and a [[central nervous system]] effect to reduce sympathetic activity (for those beta blockers that do cross the [[blood–brain barrier]], e.g. propranolol).{{citation needed|date=October 2023}}

Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen demand. Negative [[chronotropic]] properties of beta blockers allow the lifesaving property of heart rate control. Beta blockers are readily titrated to optimal rate control in many pathologic states.{{citation needed|date=October 2023}}

The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade—resulting in depression of [[sinus node]] function and [[atrioventricular node]] conduction, and prolonged [[atrium (anatomy)|atrial]] [[refractory period (cardiac)|refractory period]]s. [[Sotalol]], in particular, has additional antiarrhythmic properties and prolongs [[action potential]] duration through [[potassium channel]] blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the [[Renin–angiotensin system|renin–angiotensin–aldosterone system]], with a resultant decrease in blood pressure due to decreased sodium and water retention.