Digoxin
CLASS
- anti-arrhythmic (cardiac glycoside)
MECHANISM OF ACTION
- inotropic effect
- increased automaticity
- negative dromotropy (slowing of AV conduction)
- increased vagal tone
DIRECT:
inhibition of Na/K ATPase on the cell surface
-> increased intracellular Na+ and increased extracellular K+
-> increased intracellular Ca2+ due to Na+/Ca2+ antiporter
-> calcium-medated inotropy and increased automaticity, as well as negative dromotropy due to decreased intracellular K+
INDIRECT EFFECT:
increased vagal tone (vagomimetic effect)
PHARMACEUTICS
- IV
- tablets
DOSE
- loading = 1mg in divided doses over 24 hrs
- maintenance = 10-20mcg/kg/day
- take level 12-24 hours post administration (take long time to distribute to heart)
- therapeutic range = 0.6-1.2nmol/L
- if started in ICU only measure level @ 5-7 days
INDICATIONS
- SVT (AF): 1-3ng/mL
- Heart failure: 0.5-0.8ng/mL
- Prevention of supraventricular dysrrhythmias
ADVERSE EFFECTS
- digoxin toxicity
- ST depression (reverse tick appearance)
- tachycardias (flutter with block, VT, VF)
- bradycardia -> complete heart block
- headache
- GI symptoms
Drug interactions
- increased digoxin levels (e.g. P glycoprotein inhibitors (efflux pump in distal renal tubules and intestine), and increased bioavailability)
-> amiodarone, verapamil, quinidine, spirinolactone, clarithromycin, itraconazole, captopril - decreased digoxin levels
-> cholestyramine, oral antacids, metoclopramide, neomycin, sulfasalazine, rifampicin
PHARMACOKINETICS
- Absorption – bioavailability = 80%
- Distribution – 30% protein bound, Vd 10L/kg
- Metabolism – minimal hepatic metabolism
- Elimination – 60% renal, t ½ = 48 hrs, longer in renal failure
EVIDENCE
-> Treat toxicity with digibind (and Mg)
-> CCF + AF: rate control AF, improve mortality, exercise tolerance and symptoms
-> CCF: improved symptoms (not change in mortality and hospital admission rate)
References and Links
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
- CCC – Digoxin Toxicity
- ECG library – Digoxin Effect
- ECG library – Digoxin Toxicity
- CCC – Calcium, Digoxin Toxicity and ‘Stone Heart’ Theory
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
| INTENSIVE | RAGE | Resuscitology | SMACC