General
Preferred name
digoxin
Synonyms
12¦Â-Hydroxydigitoxin ()
12??Hydroxydigitoxin ()
Mapluxin ()
Digamex ()
Lanoxicaps ()
NSC-95100 ()
Lanoxin Pediatric ()
Lanoxin-125 ()
Lanoxin ()
Toloxin ()
Natigoxin ()
Dynamos ()
Digoxinum ()
Vanoxin ()
Lanoxin-PG ()
Lanocardin ()
Rougoxin ()
Fargoxin ()
Stillacor- ()
Digoxin Pediatric ()
Digoxin-d3 ()
P&D ID
PD010075
CAS
20830-75-5
127299-95-0
Tags
natural product
drug
available
Approved by
FDA
First approval
1975
Drug Status
approved
Drug indication
Heart failure
Cardiotonic
Congestive cardiac insufficiency
Arrhythmia
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ABSORPTION
Digoxin is approximately 70-80% absorbed in the first part of the small bowel.[A178228] The bioavailability of an oral dose varies from 50-90%, however, oral gelatinized capsules of digoxin are reported to have a bioavailability of 100%.[A178252] Tmax, or the time to reach the maximum concentration of digoxin was measured to be 1.0 h in one clinical study of healthy patients taking 0.25 mg of digoxin with a placebo.[A178369] Cmax, or maximum concentration, was 1.32 ± 0.18 ng/mlâ1 in the same study, and AUC (area under the curve) was 12.5 ± 2.38 ng/mlâ1.[A178369]; If digoxin is ingested after a meal, absorption is slowed but this does not change the total amount of absorbed drug. If digoxin is taken with meals that are in fiber, absorption may be decreased.[L6274]; ; **A note on gut bacteria**; ; An oral dose of digoxin may be transformed into pharmacologically inactive products by bacteria in the colon. Studies have indicated that 10% of patients receiving digoxin tablets will experience the degradation of at least 40% of an ingested dose of digoxin by gut bacteria. Several antibiotics may increase the absorption of digoxin in these patients, due to the elimination of gut bacteria, which normally cause digoxin degradation.[L6775] ; ; **A note on malabsorption**; ; Patients with malabsorption due to a variety of causes may have a decreased ability to absorb digoxin.[L6775] P-glycoprotein, located on cells in the intestine, may interfere with digoxin pharmacokinetics, as it is a substrate of this efflux transporter. P-glycoprotein can be induced by other drugs, therefore reducing the effects of digoxin by increasing its efflux in the intestine.[L6775]
PHARMACODYNAMICS
Digoxin is a positive inotropic and negative chronotropic drug[A178234], meaning that it increases the force of the heartbeat and decreases the heart rate.[L6253] The decrease in heart rate is particularly useful in cases of atrial fibrillation, a condition characterized by a fast and irregular heartbeat.[A178282] The relief of heart failure symptoms during digoxin therapy has been demonstrated in clinical studies by increased exercise capacity and reduced hospitalization due to heart failure and reduced heart failure-related emergency medical visits.[L6775] Digoxin has a narrow therapeutic window.[L6775]; ; **A note on cardiovascular risk**; ; Digoxin poses a risk of rapid ventricular response that can cause ventricular fibrillation in patients with an accessory atrioventricular (AV) pathway. Cardiac arrest as a result of ventricular fibrillation is fatal.[L6775] An increased risk of fatal severe or complete heart block is present in individuals with pre-existing sinus node disease and AV block who take digoxin.[L6775]; ;
DESCRIPTION
Digoxin is a cardiac glycoside similar to .
(GtoPdb)
HALF-LIFE
Digoxin has a half-life of 1.5-2 days in healthy subjects.[L6775] The half-life in patients who do not pass urine, usually due to renal failure, is prolonged to 3.5-5 days. Since most of the drug is distributed extravascularly, dialysis and exchange transfusion are not optimal methods for the removal of digoxin.[L6775]
METABOLISM
About 13% of a digoxin dose is found to be metabolized in healthy subjects. Several urinary metabolites of digoxin exist, including _dihydrodigoxin_ and _digoxigenin bisdigitoxoside_. Their glucuronidated and sulfated conjugates are thought to be produced through the process of hydrolysis, oxidation, and additionally, conjugation. The cytochrome P-450 system does not play a major role in digoxin metabolism, nor does this drug induce or inhibit the enzymes in this system.[L6775]
TOXICITY
Oral TDLO (human female): 100 ug/kg, Oral TDLO (human male): 75 ug/kg, Oral LD50 (rat): 28270 ug/kg[MSDS]; ; Digoxin toxicity can occur in cases of supratherapeutic dose ingestion or as a result of chronic overexposure.[T607] Digoxin toxicity may be manifested by symptoms of nausea, vomiting, visual changes, in addition to arrhythmia. Older age, lower body weight, and decreased renal function or electrolyte abnormalities lead to an increased risk of digoxin toxicity.[L6775];
ROE
The elimination of digoxin is proportional to the total dose, following first order kinetics. After intravenous (IV) administration to healthy subjects, 50-70% of the dose is measured excreted as unchanged digoxin in the urine. Approximately 25 to 28% of digoxin is eliminated outside of the kidney. Biliary excretion appears to be of much less importance than renal excretion.[A178228]; ; Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to extravascular tissues.[L6775]
INDICATION
Digoxin is indicated in the following conditions: 1) For the treatment of mild to moderate heart failure in adult patients.[L6775] 2) To increase myocardial contraction in children diagnosed with heart failure.[L6775] 3) To maintain control ventricular rate in adult patients diagnosed with chronic atrial fibrillation.[L6775]; ; In adults with heart failure, when it is clinically possible, digoxin should be administered in conjunction with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor for optimum effects.[L6775]; ;
MOA
Digoxin exerts hemodynamic, electrophysiologic, and neurohormonal effects on the cardiovascular system.[A178234] It reversibly inhibits the Na-K ATPase enzyme, leading to various beneficial effects. The Na-K ATPase enzyme functions to maintain the intracellular environment by regulating the entry and exit of sodium, potassium, and calcium (indirectly). Na-K ATPase is also known as the _sodium pump_[L6775]. The inhibition of the sodium pump by digoxin increases intracellular sodium and increases the calcium level in the myocardial cells, causing an increased contractile force of the heart.[L6775, A178264] This improves the left ventricular ejection fraction (EF), an important measure of cardiac function.[A178234,T613]; ; Digoxin also stimulates the parasympathetic nervous system via the vagus nerve[T607] leading to sinoatrial (SA) and atrioventricular (AV) node effects, decreasing the heart rate.[L6775,A178234] Part of the pathophysiology of heart failure includes neurohormonal activation, leading to an increase in norepinephrine. Digoxin helps to decrease norepinephrine levels through activation of the parasympathetic nervous system.[A178234]
DESCRIPTION
Potent pan-Aurora kinase inhibitor
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
29
Organisms
2
Compound Sets
23
AdooQ Bioactive Compound Library
ChEMBL Approved Drugs
ChEMBL Drugs
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Tocris Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
47
Molecular Weight
780.43
Hydrogen Bond Acceptors
14
Hydrogen Bond Donors
6
Rotatable Bonds
7
Ring Count
8
Aromatic Ring Count
0
cLogP
2.22
TPSA
203.06
Fraction CSP3
0.93
Chiral centers
21.0
Largest ring
6.0
QED
0.16
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Primary Target
Na+/K+ ATPase
MOA
ATPase inhibitor
Inhibitor
Target
Cholesterol side-chain cleavage enzyme
Na+/K+-ATPase
Therapeutic Class
Antiarrhythmic Agents
Source data
