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Cardiac Glycoside Digoxin

Cardiac Glycoside Digoxin 

Cardiac Glycoside Digoxin:

Cardiac glycosides digoxin and digitoxin are a group of drugs derived from digitalis, a substance that occurs naturally in foxglove plants and in certain toads. The most frequently used cardiac glycoside is digoxin.

Digoxin acts on the central nervous system (CNS) to slow the heart rate, thus making it useful for treating supraventricular ar- rhythmias (abnormal heart rhythms that originate above the bun- dle branches of the heart’s conduction system), such as atrial fib- rillation and atrial flutter. It also increases the refractory period (the period when the cells of the conduction system can’t conduct an impulse).

Digoxin slows ventricular rate in ATRIAL FIBRILLATION and relieves the symptoms of CHRONIC HEART FAILURE.

  • Long t1/2 of ~40hours
  • Narrow therapeutic window
  • An immune Fab (Digibind) is available for digoxin toxicity.

Mechanism of Action Cardiac glycoside digoxin:

Cardiac Glycoside Digoxin act by Inhibits Na-­‐K-­‐ATPase (Na/K Pump). This results in the increased accumulation of intracellular Na+, so increases intracellular Ca2+ (as more Na+ can be exchanged out of the cell for Ca2+ via the Na+/Ca2+ exchanger). So –POSITIVE INOTROPIC EFFECT. Central vagal stimulation causes reduced rate of conduction through AV node

Pharmacokinetics (how drugs circulate)

The intestinal absorption of digoxin varies greatly; the capsules are absorbed most efficiently, followed by the elixir form, and then tablets.

Digoxin is distributed widely throughout the body, with highest concentrations in the heart muscle, liver, and kidneys. Digoxin binds poorly to plasma proteins.

In most patients, a small amount of digoxin is metabolized in the liver and gut by bacteria. This effect varies and may be sub- stantial in some people. Most of the drug is excreted by the kid- neys as unchanged drug.

Digoxin is used in treat of heart failure because its strengthens the contraction of the ventricles by boosting release of intracellular calcium at the cell membrane, enabling stronger heart contractions.

Pharmacokinetic Parameters of Cardiac Glycoside Digoxin:

  • Bioavailability 60 to 80% (Oral)
    Protein binding 25%
    Half life36 to 48 hours (patients with normal renal
    Excretion Renal (60-80% unchanged)
    Hepatic (20-40%)
    Equations: Vd=3.8x Lean BWt.+3.1xCreatinine Clearance)
  • Population average value= 0.8 x BWt. + Creatinine Clearance
    In CHF = 0.33 x BWt. + (0.9 x Clearance)

Pharmacodynamics (how drugs act)

Digoxin may also enhance the movement of calcium into the myocardial cells and stimulate the release, or block the reuptake, of norepinephrine at the adrenergic nerve terminal.

Adverse Effects: (Common and severe)

Dysrhythmias (e.g. AV Conduction block, ectopic pacemaker activity) hypokalaemia and hypomagnaesia (usually a consequence of diuretic use), lower the threshold for digoxin toxicity.

Drug Interactions:

Many drugs can interact with digoxin.
• Antacids, barbiturates, cholestyramine resin, kaolin and pectin, neomycin, metoclopramide, rifampin, and sulfasalazine reduce the therapeutic effects of digoxin.
• Calcium preparations, quinidine, verapamil, cyclosporine, tetra- cycline, clarithromycin, propafenone, amiodarone, spironolac- tone, hydroxychloroquine, erythromycin, itraconazole, and omeprazole increase the risk of digoxin toxicity.
• Amphotericin B, potassium-wasting diuretics, and steroids tak- en with digoxin may cause hypokalemia (low potassium levels) and increase the risk of digoxin toxicity.
• Succinylcholine and thyroid preparations increase the risk of ar- rhythmias when they’re taken with digoxin.
• St. John’s wort, an herbal preparation, can increase digoxin lev- els and risk of toxicity.
Digoxin can also produce adverse reactions, mostly involving digoxin toxicity.


DIGOXIN – Action and uses
Digoxin also known as Digitalis, is a purified cardiac glycoside Digitalis lanata. Its corresponding aglycone is digoxigenin. It is used in the treatment of various heart conditions, atrial fibrillation/ Flutter, heart failure and supraventricualr parasysmal arrhythmia.

Marketed under the trade names Lanoxin, Digoxin, Digitek, and Lanoxicaps. It increase the the force of contraction and reduce the conductivity of AV node.

Dosage Protocol:
Digoxin administered orally for rapid digitalization 1500ug/ in divided over 24 hours, less urgent digitization: 250-500 ug/Day, maintenance digitalization 62.5 – 500ug/day or 125- 500ug/day and emergency digitalization: 750- 1000 ug/ 2hours followed by oral maintenance dose.


TDM/ Dose vs. Serum Concentration vs. Response:

<0.5 ug/L No clinical response
0.7ug/L +ive inotropic and conduction blocking effect
0.8-2ug/L Optimum therapeutic range
2-2.5ug/L increase risk of toxicity
>2.5ug/L GIT, CVS and CNS toxicity


Used in treatment of Congestive Heart Failure and other cardiac complications.

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