Digoxin
Systematic (IUPAC) name
4-[(3S,5R,8R,9S,10S,12R,13S,14S)-3- [(2S,4S,5R,6R)-5-[(2S,4S,5R,6R)-5- [(2S,4S,5R,6R)-4,5-dihydroxy-6-methyl- oxan-2-yl]oxy-4-hydroxy-6-methyl-oxan- 2-yl]oxy-4-hydroxy-6-methyl-oxan-2-yl] oxy-12,14-dihydroxy-10,13-dimethyl-1, 2,3,4,5,6,7,8,9,11,12,15,16,17-tetra decahydrocyclopenta[a]phenanthren- 17-yl]-5H-furan-2-one
Identifiers
CAS number	20830-75-5
ATC code	C01AA02 C01AA05 C01AA08
PubChem	30322
DrugBank	APRD00098
Chemical data
Formula	C41H64O14
Mol. mass	780.938 g/mol
Physical data
Melt. point	249.3 °C (481 °F)
Solubility in water	64.8 mg/mL (20 °C)
Pharmacokinetic data
Bioavailability	60 to 80% (Oral)
Protein binding	25%
Metabolism	Hepatic (16%)
Half life	36 to 48 hours (patients with normal renal function) 3.5 to 5 days (patients with impaired renal function)
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	A (Au), C (U.S.) Image File history File links Size of this preview: 800 × 348 pixel Image in higher resolution (1356 × 590 pixel, file size: 18 KB, MIME type: image/png) Chemical structure of digoxin created with ChemDraw. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... This article or section does not cite any references or sources. ... General Name, symbol, number carbon, C, 6 Chemical series nonmetals Group, period, block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... BIC pen cap, about 1 gram. ... The mole (symbol: mol) is the SI base unit that measures an amount of substance. ... The melting point of a crystalline solid is the temperature at which it changes state from solid to liquid. ... Solubility refers to the ability for a given substance, the solute, to dissolve in a solvent. ... This article describes water from a scientific and technical perspective. ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... A drugs efficacy may be affected by the degree to which it binds to the proteins within blood plasma. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is an organ present in vertebrates and some other animals. ... It has been suggested that Effective half-life be merged into this article or section. ... The hour (symbol: h) is a unit of time. ... In medicine (nephrology) renal function is an indication of the state of the kidney and its role in physiology. ... Look up day in Wiktionary, the free dictionary. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... Kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... Anthem Advance Australia Fair Royal anthem: God Save the Queen Capital Canberra Largest city Sydney Official languages English (de facto 1) Government Federal constitutional monarchy and parliamentary democracy  -  Queen Elizabeth II  -  Governor-General Michael Jeffery  -  Prime Minister John Howard Independence from the United Kingdom   -  Constitution 1 January 1901   -  Statute of... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from...
Legal status	S4 (Au), POM (UK), ℞-only (U.S.) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
Routes	Oral, Intravenous

Digoxin (INN) (IPA: [dɪˈdʒɒksɪn]) is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata.^[1] Its corresponding aglycone is digoxigenin. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and congestive heart failure that cannot be controlled by other medication. Digoxin preparations are commonly marketed under the trade names Lanoxin, Digitek, and Lanoxicaps. It is also available as a 0.05 mg/mL oral solution and 0.25 mg/mL or 0.5 mg/mL injectible solution. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Intravenous therapy or IV therapy is the giving of liquid substances directly into a vein. ... An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... Articles with similar titles include the NATO phonetic alphabet, which has also informally been called the “International Phonetic Alphabet”. For information on how to read IPA transcriptions of English words, see IPA chart for English. ... Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. ... Species Digitalis ferruginea Digitalis grandiflora Digitalis lanata Digitalis lutea Digitalis obscura Digitalis purpurea Digitalis is a genus of about 20 species of herbaceous biennials, perennials and shrubs in the foxglove family Scrophulariaceae. ... Binomial name Digitalis lanata The Digitalis lanata (also Woolly Foxglove or Grecian Foxglove[1]) is a species of foxglove that grows in Eastern Europe. ... In chemistry, glycosides are certain molecules in which a sugar part is bound to some other part. ... chemical structure of digoxigenin Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants Digitalis purpurea and Digitalis lanata. ... Heart Condition is a 2006 rock song from the rock musical, The Boy Who Heard Music. ... Atrial fibrillation (AF or afib) is an abnormal heart rhythm (cardiac arrhythmia) which involves the two small, upper heart chambers (the atria). ... Atrial flutter is an abnormal fast heart rhythm that occurs in the atria of the heart. ... Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ... It has been suggested that Blockbuster drug be merged into this article or section. ... A trade name, also known as a trading name or a business name, is the legal name of a business, or the name which a business trades under for commercial purposes. ...

Actions

The main pharmacological effects of digoxin are on the heart. Extracardiac effects are responsible for many of the adverse effects (see below). The heart and lungs, from an older edition of Grays Anatomy. ...

Its main cardiac effects are

• A decrease of conduction of electrical impulses through the AV node, making it a commonly used drug in controlling the heart rate during atrial fibrillation or atrial flutter.
• An increase of force of contraction via inhibition of the Na⁺/K⁺ ATPase pump (see below).

The article on electrical energy is located elsewhere. ... The atrioventricular node (abbreviated AV node) is the tissue between the atria and the ventricles of the heart, which conducts the normal electrical impulse from the atria to the ventricles. ... Heart rate is a term used to describe the frequency of the cardiac cycle. ... Atrial fibrillation (AF or afib) is an abnormal heart rhythm (cardiac arrhythmia) which involves the two small, upper heart chambers (the atria). ... Atrial flutter is an abnormal fast heart rhythm that occurs in the atria of the heart. ... In physics, force is anything that can cause a massive body to accelerate. ... Look up Contraction in Wiktionary, the free dictionary. ... Na+/K+-ATPase (also known as the Na+/K+ pump or Na+/K+ exchanger) is an enzyme (EC 3. ...

Mechanism of action

Digoxin binds to a site on the extracellular aspect of the α-subunit of the Na⁺/K⁺ ATPase pump in the membranes of heart cells (myocytes). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. The proposed mechanism is the following: inhibition of the Na⁺/K⁺ pump leads to increased Na⁺ levels, which in turn slows down the extrusion of Ca²⁺ via the Na⁺/Ca²⁺ exchange pump. Increased amounts of Ca²⁺ are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by digoxin. This is a different mechanism from that of catecholamines. Na+/K+-ATPase (also known as the Na+/K+ pump or Na+/K+ exchanger) is an enzyme (EC 3. ... The cell membrane (also called the plasma membrane, plasmalemma or phospholipid bilayer) is a semipermeable lipid bilayer common to all living cells. ... General Name, Symbol, Number sodium, Na, 11 Chemical series alkali metals Group, Period, Block 1, 3, s Appearance silvery white Standard atomic weight 22. ... An electrostatic potential map of the nitrate ion (NO3−). Areas coloured red are lower in energy than areas colored yellow An ion is an atom or group of atoms which have lost or gained one or more electrons, making them negatively or positively charged. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Standard atomic weight 40. ... The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger or exchange protein) is an antiporter ion pump membrane protein which removes calcium from cells. ... The endoplasmic reticulum or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport of proteins to be used in the cell membrane (e. ... Catecholamines are chemical compounds derived from the amino acid tyrosine that act as hormones or neurotransmitters. ...

Digoxin also increases vagal activity via its action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. This is important for its clinical use in different arrhythmias (see below). The atrioventricular node (abbreviated AV node) is the tissue between the atria and the ventricles of the heart, which conducts the normal electrical impulse from the atria to the ventricles. ...

Clinical use

Today, the most common indications for digoxin are probably atrial fibrillation and atrial flutter with rapid ventricular response. High ventricular rate leads to insufficient diastolic filling time. By slowing down the conduction in the AV node and increasing its refractory period, digoxin can reduce the ventricular rate. The arrhythmia itself is not affected, but the pumping function of the heart improves owing to improved filling. Atrial fibrillation (AF or afib) is an abnormal heart rhythm (cardiac arrhythmia) which involves the two small, upper heart chambers (the atria). ... Atrial flutter is an abnormal fast heart rhythm that occurs in the atria of the heart. ...

The use of digoxin in congestive heart failure during sinus rhythm was once standard, but is now controversial. In theory the increased force of contraction should lead to improved pumping function of the heart, but its effect on prognosis is disputable and other effective treatments are now available. Digoxin is no longer the first choice for congestive heart failure, but can still be useful in patients who remain symptomatic despite proper diuretic and ACE inhibitor treatment. It has fallen out of favor because it was proven to be ineffective at decreasing morbidity and mortality in Congestive Heart Failure. It is shown to increase quality of life, however. Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ... Sinus rhythm is indicative of normal electrical conductance of the heart. ... Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ... A diuretic (colloquially called a water pill) is any drug or herb that elevates the rate of bodily urine excretion (diuresis). ... Captopril, the first ACE inhibitor ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice. ... In medicine, epidemiology and actuarial science, the term morbidity can refer to the state of being diseased (from Latin morbidus: sick, unhealthy), the degree or severity of a disease, the prevalence of a disease: the total number of cases in a particular population at a particular point in time, the...

Digoxin is usually given by mouth, but can also be given by IV injection in urgent situations (the IV injection should be slow, heart rhythm should be monitored). The half life is about 36 hours, digoxin is given once daily, usually in 125 μg or 250 μg dosing. In patients with decreased kidney function the half life is considerably longer, calling for a reduction in dosing or a switch to a different glycoside (such as digitoxin which although having a much longer elimination half-life of around 7 days, is mainly eliminated from the body via the liver, and thus not affected by changes in renal function). Species Digitalis ferruginea Digitalis grandiflora Digitalis lanata Digitalis lutea Digitalis obscura Digitalis purpurea Digitalis is a genus of about 20 species of herbaceous biennials, perennials and shrubs in the foxglove family Scrophulariaceae. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ...

Effective plasma levels are fairly well defined, 1-2.6 nmol/l. In suspected toxicity or ineffectiveness, digoxin levels should be monitored. Plasma potassium levels also need to be closely controlled (see side effects below).

Adverse effects

The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity). Adverse effects are concentration-dependent, and are rare when plasma digoxin concentration is <0.8 μg/L.^[2] They are also more common in patients with low potassium levels (hypokalemia), since digoxin normally competes with K⁺ ions for the same binding site on the Na⁺/K⁺ ATPase pump. An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ... The therapeutic index of a medication is a comparison of the amount that causes the therapeutic effect to the amount that causes toxic effects. ... Hypokalemia is a potentially fatal condition in which the body fails to retain sufficient potassium to maintain health. ... Na+/K+-ATPase (also known as the Na+/K+ pump or Na+/K+ exchanger) is an enzyme (EC 3. ...

Common adverse effects (≥1% of patients) include: loss of appetite, nausea, vomiting, diarrhea, blurred vision, visual disturbances (yellow-green halos), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression. Less frequent adverse effects (0.1%–1%) include: acute psychosis, delirium, amnesia, shortened QRS complex, atrial or ventricular extrasystoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, heart block^[2] but when sytematically sought, the evidence for this is equivocal.^[3] The pharmacological actions of digoxin usually results in electrocardiogram (ECG) changes, including ST depression or T wave inversion, which do not indicate toxicity. PR interval prolongation, however, may be a sign of digoxin toxicity. Additionally, increased intracellular Ca²⁺ may cause a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation. The combination of increased (atrial) arrhythmogenesis and inhibited atrio-ventricular conduction (for example paroxysmal atrial tachycardia with A-V block - so-called "PAT with block") is said to be pathognomonic (i.e. diagnostic) of digoxin toxicity.^[4] “QRS” redirects here. ... Bigeminy is a heart arrhythmia in which heart beats occur in pairs with a pause between each pair. ... Ventricular tachycardia (V-tach or VT) is a fast rhythm that originates in one of the ventricles of the heart. ... Fibrillation is the rapid, irregular, and unsynchronized contraction of the muscle fibers of the heart. ... Pathognomonic (often misspelled as pathognomic) is an adjective of Greek origin (παθογνωμονικό [σύμπτωμα]), often used in medicine, which means diagnostic for a particular disease. ...

An often described but rarely seen adverse effect of digoxin is a disturbance of colour vision (mostly yellow and green colour) called xanthopsia. It has been proposed that the painter Vincent Van Gogh's "Yellow Period" may have somehow been influenced by concurrent digitalis therapy. This page is a candidate to be copied to Wiktionary using the Transwiki process. ... Vincent Willem van Gogh (sometimes erroneously pronounced [ˈvɪnsənt væn ˈɡɒf] or [ˈvɪnsənt vɑn ˈɡɔx] in British English and [ˈvɪnsənt væn ˈɡoʊ] in US English; the correct Dutch pronunciation is ) (30 March 1853 – 29 July 1890) was a Dutch Post-Impressionist artist. ...

Digoxin has an interaction with the antimalarial medication Hydroxychloroquine. Antimalarial drugs are designed to prevent or treat malaria. ... Hydroxychloroquine is an antimalarial also used to reduce inflammation and treat arthritis and lupus. ...

Other information

Digoxin has potentially dangerous interaction with verapamil,^[5] amiodarone and erythromycin. Verapamil (brand names: Isoptin®, Verelan®, Calan®) is a medical drug that acts as an L-type calcium channel blocker. ... Amiodarone belongs to a class of drugs called Vaughan-Williams Class III antiarrhythmic agent. ... Erythromycin is a macrolide antibiotic which has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. ...

In overdose, the usual supportive measures are needed. If arrhythmias prove troublesome, or malignant hyperkalaemia occurs (inexorably rising potassium level due to paralysis of the cell membrane bound ATPase-dependent Na/K pumps), the specific antidote is antidigoxin (antibody fragments against digoxin, trade names of Digibind® and Digifab®).^[6] Toxicity can also be treated with higher than normal doses of potassium. Digoxin is not removed by hemo or peritoneal dialysis with enough effectiveness to treat toxicity. General Name, Symbol, Number potassium, K, 19 Chemical series alkali metals Group, Period, Block 1, 4, s Appearance silvery white Standard atomic weight 39. ...

Researchers at Yale University looked at data from an earlier study to see if digoxin affected men and women differently. That study determined that digoxin, which has been used for centuries and makes the heart contract more forcefully, did not reduce deaths overall but did result in less hospitalization.

Researcher Dr. Harlan Krumholz said they were surprised to find that women in the study who took digoxin died more frequently (33%) than women who took a dummy pill (29%). They calculated that digoxin increased the risk of death in women by 23%. There was no difference in the death rate for men in the study.

In the news

Charles Cullen admitted in 2003 to killing as many as 40 hospital patients with overdoses of heart medication—usually digoxin—at hospitals in New Jersey and Pennsylvania over his 16-year career as a nurse. On March 10, 2006 he was sentenced to 18 consecutive life sentences and is not eligible for parole for 397 years.^[7] Charles Cullen (b. ...

See also

• Acetyldigoxin
• Cardiac glycoside
• Digitoxin
• Digitalis
• Digoxigenin

The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. ... Species Digitalis ferruginea Digitalis grandiflora Digitalis lanata Digitalis lutea Digitalis obscura Digitalis purpurea Digitalis is a genus of about 20 species of herbaceous biennials, perennials and shrubs in the foxglove family Scrophulariaceae. ... Species About 20 species, including: Digitalis cariensis Digitalis ciliata Digitalis davisiana Digitalis dubia Digitalis ferruginea Digitalis grandiflora Digitalis laevigata Digitalis lanata Digitalis leucophaea Digitalis lutea Digitalis obscura Digitalis parviflora Digitalis purpurea Digitalis thapsi Digitalis trojana Digitalis viridiflora Digitalis is a genus of about 20 species of herbaceous biennials, perennials and... chemical structure of digoxigenin Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants Digitalis purpurea and Digitalis lanata. ...

References

1. ^ A. Hollman (1996). "Digoxin comes from Digitalis lanata" (letter). British Medical Journal 312 (7035): 912. 
2. ^ ^{a b} Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
3. ^ Thompson, D.F.; Carter, J.R. (1993). "Drug-induced gynecomastia.". Pharmacotherapy 13 (1): 37-45. PMID 8094898. 
4. ^ Doering, W.; Konig, E.; Sturm, W. (1977). "Digitalis intoxication: specifity and significance of cardiac and extracardiac symptoms. part I: Patients with digitalis-induced arrhythmias (author's transl)". Z Kardiol 66 (3): 121-8. PMID 857452. 
5. ^ Kaplanski, J.; Weinhouse, E.; Topaz, M.; Genchik, G. (1983). "Verapamil and digoxin: interactions in the rat.". Res Commun Chem Pathol Pharmacol 42 (3): 377-88. PMID 6665298. 
6. ^ Flanagan, R.J.; Jones, A.L. (2004). "Fab Antibody Fragments: Some Applications in Clinical Toxicology" (full text (subscription)). Drug Safety 27 (14): 1115-1133. PMID 15554746. 
7. ^ "Victims' families set to confront killer", USA Today, 1 Jan 2006. 

The British Medical Journal (BMJ) is a medical journal published weekly in the United Kingdom by the British Medical Association (BMA)which published its first issue in 1845. ... USA Today is a national American daily newspaper published by the Gannett Company. ...

Further reading

• Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology, 5th edition. Edinburgh: Churchill Livingstone; 2003. ISBN 0-443-07145-4
• Summary of product characteristics, Digoxin 0,125 mg, Zentiva a.s.
• Lüllmann. Pharmakologie und Toxikologie (15th edition), Georg Thieme Verlag, 2003. ISBN 3-13-368515-5