What is the main mechanism of action of digoxin?
Positive inotropic effects: Digoxin inhibits the Na+/K+ pumps of the cardiac cell membranes. This increases intracellular Na+ levels. High intracellular Na+ levels facilitate Ca++ influx into the cells. Increased intracellular Ca++ equals STRONG MUSCLE CONTRACTIONS.
What is an additional mechanism of action of digoxin?
Beneficial neurohormonal effects: Occur at lower doses & are independent of inotropic activity. Digoxin reduces SNS activation & increases parasympathetic activity leading to a decrease in heart rate, thus enhancing diastolic flling. The vagal effects slow SA node conduction.
Explain the pharamacokinetics of digoxin.
Half-life = 1.5 days; much longer if severely renally impaired.
Excreted by kidney & metabolized by liver, Substrate of CYP3A4 (% metabolized is pt variable)
Distributed widely in body tissues = LARGE Vd
Narrow Therapeutic Window!
What are the therapeutic serum levels of digoxin for HF?
Therapeutic serum levels = generally 0.5-1.0 ng/mL is acceptable for HF. Positive inotropic benefits probably occur at slightly higher levels ~0.8 ng/mL or higher.
What are the therapeutic uses of digoxin?
CHF (not DOC): improves symptoms, QOL, LVEF, & exercise tolerance but does not improve survival.
Treat supraventricular tachyarrythmias (A. fib)
Explain the digitalizing dose of digoxin & where it may be seen?
Loading doses are sometimes used for tachyarrhythmias to overcome the large Vd & rapidly achieve adequate serum levels. Loading doses are only used when a quick onset of action is needed & they are usually only done in a hospital setting. Using loading doses increases the risk of supratherapeutic levels & toxicity.
Explain the maintenance dose of digoxin.
If digitalization is not necessary, it is SAFER to just begin giving the usual expected maintenance dose.
Usual maintenance dose = 0.125-0.25 mg daily. Dosing is extremely pt variable
Elderly pts & smaller pts usually receive 0.125 mg daily.
Renally impaired pts may require every other day dosing.
What adverse effects may indicate digoxin toxicity?
N/V, loss of appetite
Fatigue, weakness, dizziness, headache, neuralgia, confusion, delirium, psychosis
Vision: blurred vision, haloes, photophobia, red-green or yellow-green tinted vision
Almost any kind of cardiac dysrhythmia
Sinus bradycardia with pulse less than 60 bpm
What population is at increased risk of digoxin toxicity?
Elderly are at increased risk of toxicity due to decreased renal function, increased myocardial sensitivity, & frequent use of diuretics, laxatives, & other interacting medications.
What is the treatment of digoxin toxicity?
Give K+ supplements! (Increase K+ to high/normal - will have a protective effect on the heart).
Treat any arrythmias with the appropriate agent.
Digoxin Immune Fab (Digibind) - used in serious overdose situations. Binds with molecules of digoxin in the blood, inactivating it. The molecules are then excreted by the kidney.
What must you remember after administering Digoxin Immune Fab in regards to labs?
Do not expect digoxin levels to go down after Digibind is administered. Although inactivated, the drug is still present in the blood stream & will be detected by serum assay. Levels may even be reported as higher than before Digibind. Monitor pt response as an indication of Digibind effectiveness rather than repeat serum levels. Also digoxin has a longer half life than Digibind.
Normal digoxin levels in the prexence of _________ could indicate toxicity.
Low blood K+ naturally blocks Na+/K+ pumps - increases risk of digoxin toxicity
What conditions will predispose pts to digoxin toxicity? Which drugs contribute to these conditions?
Hypokalemia, Hypercalcemia, & Hypomagnesemia.
Diuretics & laxatives may cause hypokalemia.
What are additional common drug reactions with digoxin?
CYP3A4 inhibitors will increase digoxin levels! (several antidysrhythmics)
Antacids may reduce bioavailability.
AV heart block when used w/ B-blockers, diltiazem, verapamil.
Oral antibiotics may alter GI flora, which can alter digoxin absorption.
Colestyramine can bind intestinally & inhibit absorption.
Explain the basics of monitor serum levels of digoxin & the times when they are checked.
Only serum levels at steady-state will accurately reflect the current maintenance dose (7 days for pts with normal renal function, 14 days otherwise).
Serum levels usually checked w/in 48 hrs & at 7 & 14 days after the addition or deletion of a potentially interacting med or a change in dose. It is recommended to obtain serum levels at least 6 hrs after last dose. (optimal = 12 hrs after)