Cardiac glycoside · Rate control
Digoxin
Indications
- AF rate control, especially with HFrEF or hypotension where diltiazem is harmful; often added to a beta-blocker
- HFrEF still symptomatic on guideline therapy, to cut hospitalization (no mortality benefit in the DIG trial)
- Heart failure in infants and children (label)
Dosing
| Where | Dose |
|---|---|
| Electrolytes, drugs and temperature | Digoxin effect: Scooped ST depression; toxicity: almost any arrhythmia, classically atrial tachycardia with block, bidirectional VT |
| Other ICU drugs | Digoxin: Reduce and follow levels |
On the quick cards
Mechanism of action
Digoxin binds the extracellular face of the Na⁺/K⁺-ATPase α subunit and locks the pump, competing with K⁺: hypokalemia increases binding and toxicity, and hyperkalemia reduces it. The rise in intracellular Na⁺ slows Ca²⁺ extrusion by the Na⁺/Ca²⁺ exchanger, so the sarcoplasmic reticulum releases more Ca²⁺ per beat (positive inotropy). Raised vagal tone and baroreceptor sensitivity slow the SA node and AV conduction, the basis of rate control. At toxic levels Ca²⁺ overload causes delayed afterdepolarizations while vagal effects deepen block, giving ectopy with block.
Pharmacology
- Cardiovascular: modest inotropy in HFrEF with a slower heart rate; outside the classic Vaughan Williams classes
- Electrophysiology: longer AV-node refractoriness (PR), shorter atrial and ventricular refractoriness (short QT), scooped ST depression
- Rate control is vagal, so it fails with exercise, fever, sepsis or catecholamine infusions
- GI and CNS: anorexia, nausea and vomiting (chemoreceptor trigger zone), confusion and yellow-green vision with toxicity
- Metabolic: acute overdose raises K⁺; chronic toxicity often comes with diuretic-induced hypokalemia
Pharmacokinetics
| Onset | IV 5–30 min; oral 0.5–2 h (label) |
|---|---|
| Peak | IV 1–4 h; oral 2–6 h (label) |
| Half-life | 1.5–2 days; 3.5–5 days in anuria (label) |
| Distribution | Vd 475–500 L, mostly muscle; a 6–8 h distribution phase, so draw levels 6 h or more after a dose; dose by lean weight (label) |
| Protein binding | About 25% |
| Metabolism | About 13%, not by CYP; gut bacteria inactivate oral doses in about 1 in 10 patients (label) |
| Elimination | Kidneys: 50–70% unchanged by filtration and P-gp secretion (label) |
| Dialysis | Not removed, because most of it is bound in tissue |
| Serum levels | 0.5–2 ng/mL (label), adverse effects likelier above 1.2; 0.5–0.9 ng/mL in heart failure (DIG analyses) |
Chemistry
- A cardiac glycoside from Digitalis lanata: a steroid core with an unsaturated five-membered lactone at C17 and three digitoxose sugars at C3
- A 12-hydroxyl makes it more polar than digitoxin, hence renal clearance and a shorter half-life
- Neutral at body pH and a single natural stereoisomer; practically insoluble in water (label)
- Injection 0.25 mg/mL in 40% propylene glycol and 10% ethanol; give IV over 5 min or more, undiluted or diluted at least 4-fold, since less dilution can precipitate (label)
Adverse effects and cautions
In the one-pagers
- Toxidromes and AntidotesCardiotoxic drugs: Digoxin: Digoxin Fab 10–20 vials (acute, unknown); 6 if chronic: Dysrhythmias or K over 5.5; levels unreliable after
- Rhythm GallerySinus, atrial and junctional: Junctional: regular, narrow, about 40–60/min; P waves absent, inverted or after the QRS. Symptomatic: treat as bradycardia; think of digoxin.
- Heart FailureDiuretic monitoring: Low K or Mg raises the risk of digoxin toxicity. MRAs and ACEi/ARB/ARNi raise K; check labs before giving.
- Electrolyte ImbalancesCalcium: salts and corrected calcium: In the ICU, measure ionized Ca; the formula often misses true hypocalcemia. Never mix calcium with bicarbonate, phosphate or ceftriaxone. Caution with digoxin.
- Fluids, IV Therapy and ElectrolytesElectrolytes: signs and nursing priorities: Low K: Weakness, cramps, ileus, dysrhythmias: ST sag, flat T, U wave: Replace K, check Mg; monitor; digoxin risk
- Lab Values to KnowTherapeutic drug levels: Digoxin: 0.5–2.0 ng/mL; heart failure often 0.5–0.9: Nausea, yellow-green vision, bradycardia, arrhythmias
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Sources
- FDA label: Lanoxin injection (2026)
- FDA label: Digoxin tablets (2024)
- FDA label: DigiFab (2026)
- DIG trial (1997)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.