What is digoxin and what are its uses?
- Heart failure
- Atrial fibrillation & flutter
What are the positive inotropic effects of digoxin and its use?
- inhibits the Na, K-ATPase
- increases intracellular calcium = increases contractility
use: increases CO in HF due to systolic dysfunction
What are the chronotropic effects of digoxin and its use?
- negative effects via parasympathetic activity and vagal tone
- shortens atrial contraction and prolongs AV nodal refractory period
use: atrial fibrillation and flutter
Why is digoxin not given as an IM injection?
due to erratic absorption and injection site pain (can't account for how pt reacts to it)
What are the bioavailabilities of the various dosage forms of digoxin?
- IV = 100%
- Capsules = 90%
- Elixir = 80%
- Tablets = 70%
What is the IV to oral dose conversion for digoxin?
increase by 25%
What is the oral to IV dose conversion for digoxin?
decrease by 25%
Where is digoxin absorbed?
What factors decrease absorption of digoxin?
- high fiber meals (tablets and capsules)
- malabsorption syndromes
- chemotherapy and radiation
- antacids, cholestyramine, metoclopramide
What drugs increase absorption of digoxin because they are p-glycoprotein inhibitors?
Where is digoxin distributed in the body?
Lean organ tissue like muscle, heart, kidneys and liver
How does physical exercise affect distribution of digoxin?
increases the affinity for distribution to skeletal and heart muscles
How does obesity effect the distribution of digoxin?
not effected by obesity
How does renal failure and hyperkalemia effect the distribution of digoxin?
Vd decreased by renal failure and hyperkalemia
Where is digoxin metabolized?
- Major site: GI tract (hydrolyzed by stomach acid)
- Reduced by GI bacteria to inactive metabolites
- macrolide antibiotics (erythromycin & clarithromycin) increase absorption by 30%
How is digoxin excreted?
- 75% unchanged in the kidneys via glomerular filtration and tubular secretion
- 25% biliary & hepatic elimination (enterohepatic circulation)
- Half-life ~36 hours (can be given QOD d/t half-life)
What factors decrease the clearance of digoxin?
- heart failure
What factors increase clearance of digoxin?
- digoxin immune fab (digibind)
What is the dosing of digoxin?
BASED ON IDEAL BODY WEIGHT!
- 1-1.5 mg orally, 0.5-1 mg IV
- administer 50% of dose initially, then 25% of dose at 6 and 12 hours
- typically not administered when used to treat heart failure
- 0.125-0.5 mg daily
- should be based on patients clinical response, digoxin concentration and renal function
What are the reference ranges for TDM for CHF and AF?
CHF: 0.5 - 1.0 mcg/L
AF: 0.8 - 2.0 mcg/L
When should digoxin levels be checked?
- if clinical deterioration occurs
- to assess compliance
- acute changes iin renal function
- when toxicity is suspected
- when patient has a new interaction (either drug or condition)
When should digoxin serum samples be drawn for TDM?
- If LD given: within 12-24 hours after the initial dose
- If no LD given: wait 3-5 days before obtaining serum levels
- Following IV MD: no sooner than 6 hours after dose administration
- During MD therapy it is also appropriate to order trough concentrations instead of 4-6 hours after the dose
- If dose adjusted: wait 5-7 days before assessing serum concentrations
When does digoxin toxicity occur?
May occur at therapeutic concentrations but most common with serum concentrations > 2.0 mcg/L
What are the cardiac toxicities associated with digoxin?
- Atrial tachycardia with 2nd and 3rd degree AV block
- Fatal ventricular arrhythmias
What are the non-cardiac toxicities of digoxin?
- GI: nausea, vomiting, diarrhea, abdominal pain
- CNS: headache, fatigue, confusion, vertigo
- Visual disturbances: blurred or yellow-green halo vision
What effects does digoxin toxicity have on electrolytes?
- Potassium: hypokalemia potentiates effects of digoxin
- Calcium: hypercalcemia facilitates toxicity
- Magnesium: hypomagnesmia potentiates proarrhythmic effects
How can digoxin overdoses be treated?
digoxin immune Fab (digibind)