Editing Digitalis (section)

====Mechanism of action====
Digitalis works by inhibiting [[sodium-potassium ATPase]]. This results in an increased intracellular concentration of sodium ions and thus a decreased concentration gradient across the cell membrane. This increase in intracellular sodium causes the Na/Ca exchanger to reverse potential, i.e., transition from pumping sodium into the cell in exchange for pumping calcium out of the cell, to pumping sodium out of the cell in exchange for pumping calcium into the cell. This leads to an increase in cytoplasmic calcium concentration, which improves cardiac contractility.<ref>{{cite journal |doi=10.1016/0165-6147(85)90136-1 |title=Sodium ion and the cardiac actions of digitalis |journal=Trends in Pharmacological Sciences |year=1985 |pages=296–298 |volume=6 |last1=Akera |first1=Tai |last2=Brody |first2=Theodore M.}}</ref> Under normal physiological conditions, the cytoplasmic calcium used in cardiac contractions originates from the [[sarcoplasmic reticulum]], an intracellular organelle that stores calcium. Human newborns, some animals, and patients with chronic heart failure lack well developed and fully functioning sarcoplasmic reticula and must rely on the Na/Ca exchanger to provide all or a majority of the cytoplasmic calcium required for cardiac contraction. For this to occur, cytoplasmic sodium must exceed its typical concentration to favour a reversal in potential, which naturally occurs in human newborns and some animals primarily through an elevated heart rate; in patients with chronic heart failure it occurs through the administration of digitalis. As a result of increased contractility, [[stroke volume]] is increased. Ultimately, digitalis increases cardiac output (cardiac output = stroke volume x heart rate). This is the mechanism that makes this drug a popular treatment for congestive heart failure, which is characterized by low cardiac output.

Digitalis also has a vagal effect on the [[parasympathetic nervous system]], and can be used to slow the ventricular rate during [[atrial fibrillation]] (unless there's [[Wolff–Parkinson–White syndrome|an accessory pathway]], when it can paradoxically increase the heart rate).<ref>{{cite journal |last1=Fuster |first1=Valentin |last2=Rydén |first2=Lars E. |last3=Asinger |first3=Richard W. |last4=Cannom |first4=David S. |last5=Crijns |first5=Harry J. |last6=Frye |first6=Robert L. |last7=Halperin |first7=Jonathan L. |last8=Kay |first8=G. Neal |last9=Klein |first9=Werner W. |last10=Lévy |first10=Samuel |last11=McNamara |first11=Robert L. |last12=Prystowsky |first12=Eric N. |last13=Wann |first13=L. Samuel |last14=Wyse |first14=D. George |last15=Gibbons |first15=Raymond J. |last16=Antman |first16=Elliott M. |last17=Alpert |first17=Joseph S. |last18=Faxon |first18=David P. |last19=Fuster |first19=Valentin |last20=Gregoratos |first20=Gabriel |last21=Hiratzka |first21=Loren F. |last22=Jacobs |first22=Alice K. |last23=Russell |first23=Richard O. |last24=Smith |first24=Sidney C. |last25=Klein |first25=Werner W. |last26=Alonso-Garcia |first26=Angeles |last27=Blomström-Lundqvist |first27=Carina |last28=de Backer |first28=Guy |last29=Flather |first29=Marcus |last30=Hradec |first30=Jaromir |last31=Oto |first31=Ali |last32=Parkhomenko |first32=Alexander |last33=Silber |first33=Sigmund |last34=Torbicki |first34=Adam |title=ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology |journal=Circulation |date=23 October 2001 |volume=104 |issue=17 |pages=2118–2150 |doi=10.1161/circ.104.17.2118 |pmid=11673357 |language=en |issn=0009-7322|doi-access=free }}</ref> The dependence on the vagal effect means digitalis is not effective when a patient has a high [[sympathetic nervous system]] drive, which is the case with acutely ill persons, and also during exercise.<ref>{{Cite journal |date=1985-05-01 |title=Digitalis and the autonomic nervous system |journal=Journal of the American College of Cardiology |language=en |volume=5 |issue=5 |pages=35A–42A |doi=10.1016/S0735-1097(85)80461-7 |issn=0735-1097 |last1=Watanabe |first1=August M. |pmid=3886751|doi-access=free }}</ref><ref>{{Cite journal |last1=Tonkon |first1=M. J. |last2=Lee |first2=G. |last3=DeMaria |first3=A. N. |last4=Miller |first4=R. R. |last5=Mason |first5=D. T. |date=December 1977 |title=Effects of digitalis on the exercise electrocardiogram in normal adult subjects |url=https://pubmed.ncbi.nlm.nih.gov/923306/ |journal=Chest |volume=72 |issue=6 |pages=714–718|doi=10.1378/chest.72.6.714 |issn=0012-3692 |pmid=923306}}</ref>