Editing Digoxin (section)

=== Pharmacodynamics ===
[[File:Signal-averaged ECG with digoxin.png|class=skin-invert-image|thumb|250px|Signal-averaged [[electrocardiography|ECG]] from a person taking digoxin, explaining ST depressions in mainly [[precordial lead]]s V4 and V5]]
Digoxin's primary mechanism of action involves inhibition of the sodium potassium adenosine triphosphatase ([[Na+/K+ ATPase]]), mainly in the [[myocardium]].<ref name="sciencedirect.com"/> This inhibition causes an increase in intracellular [[sodium]] levels, resulting in decreased activity of the [[sodium-calcium exchanger]], which normally imports three extracellular [[sodium ion]]s into the cell and transports one intracellular [[calcium]] ion out of the cell. The reversal of this exchanger, triggered by the increase in intracellular sodium, results in an increase in the intracellular calcium concentration that is available to the contractile [[protein]]s. The increased calcium concentrations lead to the binding of more calcium to [[troponin C]], which results in increased [[inotropy]]. Increased intracellular calcium lengthens phase 4 and phase 0 of the [[cardiac action potential]], which leads to a decrease in heart rate.<ref>{{ cite book | editor = Tripathi |editor-first=K. D. | title = Essentials of Medical Pharmacology | edition = 6th | pages = 498 | publisher = Jaypee Publications | location = New Delhi | isbn = 978-81-8448-085-6 |date=2008-12-01 }}</ref> Increased amounts of Ca<sup>2+</sup> also leads to increased storage of calcium in the [[sarcoplasmic reticulum]], causing a corresponding increase in the release of calcium during each action potential. This leads to increased contractility (the force of contraction) of the heart without increasing heart energy expenditure.{{citation needed|date=June 2017}}

The inhibition of the sodium pump may also improve [[baroreceptor]] sensitivity in heart failure and may explain some of the neurohormonal effects of digoxin.<ref name="Wang 1990">{{cite journal | vauthors = Wang W, Chen JS, Zucker IH | title = Carotid sinus baroreceptor sensitivity in experimental heart failure | journal = Circulation | volume = 81 | issue = 6 | pages = 1959–66 | date = June 1990 | pmid = 2344687 | doi = 10.1161/01.cir.81.6.1959 | doi-access =  }}</ref>

Digoxin also has important [[parasympathetic]] effects, particularly on the [[atrioventricular node]].<ref name="Gheorghiade 2004">{{cite journal | vauthors = Gheorghiade M, Adams KF, Colucci WS | title = Digoxin in the management of cardiovascular disorders | journal = Circulation | volume = 109 | issue = 24 | pages = 2959–64 | date = June 2004 | pmid = 15210613 | doi = 10.1161/01.cir.0000132482.95686.87 | s2cid = 33752611 | doi-access = free }}</ref> While it does increase the magnitude of [[myocardium|myocardial]] contractility, the duration of the contraction is only slightly increased. Its use as an [[antiarrhythmic drug]], then, comes from its direct and indirect parasympathetic stimulating properties. [[Vagus nerve]] stimulation slows down conduction at the AV node by increasing the refractory period of cardiac myocytes. The slowed AV node gives the ventricles more time to fill before contracting. This negative [[chronotropic]] effect is synergistic with the direct effect on cardiac pacemaker cells. The arrhythmia itself is not affected, but the pumping function of the heart improves, owing to improved filling.

Overall, the heart rate is decreased while [[stroke volume]] is increased, resulting in a net increase in [[blood pressure]], leading to increased tissue [[perfusion]]. This causes the myocardium to work more efficiently, with optimized [[hemodynamic]]s and an improved ventricular function curve.

Other electrical effects include a brief initial increase in [[action potential]], followed by a decrease as the [[potassium|K<sup>+</sup>]] conductance increases due to increased [[intracellular]] amounts of [[calcium|Ca<sup>2+</sup>]] ions. The [[refractory period (physiology)|refractory period]] of the [[atrium (heart)|atria]] and [[Ventricle (heart)|ventricles]] is decreased, while it increases in the [[sinoatrial node|sinoatrial]] and AV nodes. A less negative resting membrane potential is made, leading to increased irritability.

The conduction velocity increases in the atria, but decreases in the AV node. The effect upon [[Purkinje fiber]]s and ventricles is negligible. [[Automaticity]] is also increased in the [[atrium (heart)|atria]], AV node, Purkinje fibers, and ventricles.<ref>{{cite book | vauthors = Cunningham L |date=2018 |title=Cardiology Secrets |url=https://www.sciencedirect.com/book/9780323478700/cardiology-secrets |location= |publisher=Elsevier |pages=241–252 |isbn=978-0-323-47870-0 |access-date=2021-03-28 |archive-date=2021-04-20 |archive-url=https://web.archive.org/web/20210420043214/https://www.sciencedirect.com/book/9780323478700/cardiology-secrets |url-status=live }}</ref>

[[ECG]] changes seen in people taking digoxin include increased PR interval (due to decreased AV conduction) and a shortened QT interval. Also, the [[T wave]] may be inverted and accompanied by ST depression. It may cause AV junctional rhythm and [[ectopic beat]]s (bigeminy) resulting in [[ventricular tachycardia]] and [[ventricular fibrillation|fibrillation]].

Digoxin is also an [[M2 receptor]] [[muscarinic agonist]].<ref>{{cite book | vauthors = King GS, Goyal A, Grigorova Y, Hashmi MF | chapter = Antiarrhythmic Medications | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK482322/ |title = StatPearls | location = Treasure Island (FL) |publisher=StatPearls Publishing |access-date=7 May 2023 |date=2023 | pmid = 29493947 }}</ref>