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What is digoxin and what are its uses?
Cardiac glycoside
- Uses:
- Heart failure
- Atrial fibrillation & flutter
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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
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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
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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)
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What are the bioavailabilities of the various dosage forms of digoxin?
- IV = 100%
- Capsules = 90%
- Elixir = 80%
- Tablets = 70%
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What is the IV to oral dose conversion for digoxin?
increase by 25%
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What is the oral to IV dose conversion for digoxin?
decrease by 25%
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Where is digoxin absorbed?
small intestine
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What factors decrease absorption of digoxin?
- high fiber meals (tablets and capsules)
- malabsorption syndromes
- chemotherapy and radiation
- antacids, cholestyramine, metoclopramide
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What drugs increase absorption of digoxin because they are p-glycoprotein inhibitors?
- amiodarone
- verapamil
- quinidine
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Where is digoxin distributed in the body?
Lean organ tissue like muscle, heart, kidneys and liver
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How does physical exercise affect distribution of digoxin?
increases the affinity for distribution to skeletal and heart muscles
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How does obesity effect the distribution of digoxin?
not effected by obesity
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How does renal failure and hyperkalemia effect the distribution of digoxin?
Vd decreased by renal failure and hyperkalemia
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Where is digoxin metabolized?
- Major site: GI tract (hydrolyzed by stomach acid)
- Liver(16%)
- Reduced by GI bacteria to inactive metabolites
- macrolide antibiotics (erythromycin & clarithromycin) increase absorption by 30%
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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)
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What factors decrease the clearance of digoxin?
- heart failure
- hypothyroidism
- verapamil
- amiodarone
- itraconazole
- hypokalemia
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What factors increase clearance of digoxin?
- hyperthyroidism
- digoxin immune fab (digibind)
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What is the dosing of digoxin?
BASED ON IDEAL BODY WEIGHT!
- LD:
- 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
- MD:
- 0.125-0.5 mg daily
- should be based on patients clinical response, digoxin concentration and renal function
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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
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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)
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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
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When does digoxin toxicity occur?
May occur at therapeutic concentrations but most common with serum concentrations > 2.0 mcg/L
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What are the cardiac toxicities associated with digoxin?
- Proarrhythmic
- Bradycardia
- Atrial tachycardia with 2nd and 3rd degree AV block
- Fatal ventricular arrhythmias
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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
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What effects does digoxin toxicity have on electrolytes?
- Potassium: hypokalemia potentiates effects of digoxin
- Calcium: hypercalcemia facilitates toxicity
- Magnesium: hypomagnesmia potentiates proarrhythmic effects
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How can digoxin overdoses be treated?
digoxin immune Fab (digibind)
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