Digoxin

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Digoxin Toxicity:

Digoxin Toxicity By : chethan Kumar p

Cardiac glycosides:

Cardiac glycosides

Cardiac glycosides:

Cardiac glycosides Two drugs (digoxin, digitoxin) Well absorbed orally 10% of population have bacteria in the gut, which inactivate digoxin, needing an increased dose in such Beware of using antibiotics in such patients Digoxin has a very narrow ther. Margin

digoxin:

digoxin Reversibly combine with sodium-potassium ATPase of the cardiac cell membrane Results in inhibition of pump activity This leads to in intracellular Na conc. This favors Ca ions in the cell Ca levels result in increased systolic force of contraction

digoxin:

digoxin Taken orally Renal clearance proportional to Cr Cl To be used with extreme caution in patients suffering from renal impairment

Na/K ATPase inhibition:

Na/K ATPase inhibition

Additional MOA:

Additional MOA Force of contraction resembles to that of the normal heart Improved circulation leads to reduced sympathetic activity This reduces PVR All this leads to reduction in HR Vagal tone is enhanced Finally myocardial O 2 demand is reduced

Electrophysiological effects on the heart :

Electrophysiological effects on the heart

Uses:

Uses Congestive heart failure Cardiac arrhythmias

Absorption:

Absorption 60-85% absorbed after oral administration of tablets 75-80% absorbed after administration of elixir 90-100% absorbed from liquid filled capsules 80% absorbed from intramuscular injection (not recommended) 100% absorbed from intravenous dose 40% degraded by intestinal bacteria–1 in 10

Distribution:

Distribution 6-8 hour tissue distribution phase Widely distributed Early high levels of serum concentration do not reflect action at desired site Receptor binding is the rate limiting step 25% protein bound Correlates well with lean body tissue Crosses the placenta and enters breast milk – Pregnancy category C

Elimination:

Elimination 16% is metabolized by liver Metabolism not dependent on the cytochrome P450 system and is not known to induce or inhibit it 50-70% is excreted almost entirely unchanged by the kidneys Excretion proportional to GFR Half life: 36-48 hours, increased in renal impairment Not effectively removed by dialysis

dynamics:

dynamics Time to peak effect: 1-4 hours (IV) and 2-6 hours (PO) Therapeutic serum digoxin levels : 0.5-2ng/ mL (6 hours after dose) Inhibits Na-K ATPase Increases myocardial contraction Increased cardiac output Improved circulation Improved tissue perfusion Decreases conduction through AV node Decreased heart rate

Toxicity:

Toxicity Toxicity level: >2.4ng/mL 1/3 of patients have toxic symptoms at <2.0ng/mL First signs of toxicity: Abdominal pain Anorexia Nausea Vomiting Visual disturbances Bradycardia Arrhythmias Confusion Delirium Infants: arrhythmias

Cardiotoxicity:

Cardiotoxicity Serious adverse reaction May result in 1 st , 2 nd or 3 rd degree block Ventricular dysrhythmias Three cardiac altered functions Suppression of AV conduction Increased automaticity Decreased refractory period in ventricles Dilantin and Lidocaine effective treatment

Precautions & contraindication:

Precautions & contraindication HYPOKALEMIA: enhance digoxin toxicity by increasing its binding to Na+k+ ATPase. Elderly, renal or severe hepatic disease: patients are more sensitive. Myxoedema: these patients eliminate digoxin more slowly cumulative toxicity can occur.

Drug Interactions:

Drug Interactions Thiazide and Loop diuretics – cause hypokalemia Cortisone – Na retention and K loss Antiarrhythmics – increase serum levels of digoxin Spironolactone – increases half life of digoxin Beta blockers – additive bradycardia All of these increase the risk of toxicity

Implications:

Implications Monitor pulse prior to administration Monitor blood pressure throughout therapy Monitor ECG throughout IV administration and periodically during therapy, as new arrhythmias and bradycardia may develop Kidney and thyroid dysfunction alters dosage required Increased age increases risk of toxicity

Treatment:

Treatment Discontinuation of digitalis may be enough Hypokalemia and adequate renal function Potassium salts Arrhythmias Medications or ventricular pacing Life threatening arrhythmias Digibind Digibind Digoxin immune Fab Binds with digoxin, forming complex molecules Excreted in urine