Cardiac Glycosides Pharmacology 

Drugs

• Digoxin obtained from digitalis lanata (the only available drug)
• Digitoxin-obtained from digitalispurpura
• Strophthanin
• Ouabain

Bufotoxin-obtained from the skin of a poisonous toad -Bufotoad.

Digitalis Plant or Foxglove Plant - Flower

• Color - Purple to pink
• Shape - Trumpet-like.

Also read: CVS Pharmacology Important One-liners

Digoxin

Mechanism of Action

MOA-1

• Acts on the myocardium
• Inhibits Na+K+ ATPase on the muscles of the heart
• Positive inotropic drug
• Increases force of contraction
• Increases cardiac output

MOA-2

Inhibits

• SA node →Negative chronotropic (reduces HR)
• AV node → Negative dromotropic (reduced AV node conduction)
• Digoxin stimulates vagus nerve
• Inhibits SA and AV node
• Vagomimetic effect of digoxin
• Digoxin blocks the potassium site of Na+K+ATPase
  • Hyperkalemia → Decreases the effect of binding of Digoxin
  • Hypokalemia → Increased toxicity of digoxin → Increased binding of Digoxin leads to
    • arrhythmias.
    • Digoxin is contraindicated in hypokalemia (K+ <3.5 meg/l).
    • Digoxin overdose → Hyperkalemia in blood.

Uses 

• DOC: Chronic heart failure
  • Positive inotropic drug → ↑ Cardiac output
• Used in the treatment of Atrial flutter and atrial fibrillation (SVT)
  • Aim - To prevent VT/VF by blocking AV nodes → Dromotropic effect.

Also read: Renal Pharmacology—High-Yield For INI-CET

Digoxin administration

• Atrial flutter (Single ectopic gives high-speed impulse to the ventricles)
• Increased levels of sodium inside the cell
• Create multiple ectopics
• Most of the impulses cancel each other
• Better AV node block
• Atrial fibrillation

Pharmacokinetics of Digoxin

Absorption

• Route of administration: Oral-CHF → Digoxin is the only drug
• IV-AHF

Distribution

• Vd-High Vd: 450 liters → Deposits in myocardium → Hemodialysis in digoxin toxicity is not effective as the drug is not present in the blood.
• T ½ : 40 hours → loading dose required for immediate effect
• Onset of action: It takes 5-8 days to show the effect of digoxin.

Metabolism

• Not metabolized in the liver
• Safe to use in liver disease

Elimination

• Unchanged in urine (kidney) by P-glycoprotein transporter
• Contraindicated in renal diseases

Also read: Pharmacology Image Based Questions for NEET PG 2025

Therapeutic Index

Digoxin is a narrow therapeutic index drug (Low safety margin) → Requires TDM. Therapeutic range: 0.5-2.0 ng/ml. Digitoxin is excreted in bile and it is safe for renal disease.

Digoxin Toxicity

• No role of hemodialysis due to large Vd.
• Antidote: Digibind or Digifab (FAB MAb against digoxin)
  • The FAB fragment binds to Digitoxin.
• Digibind is an Orphan drug (Rare indication)
• If Digibind is unavailable, Potassium chloride is used to treat Digoxin toxicity.
  • More potassium in the blood competes against digoxin and reduces digoxin toxicity.

Side Effects

Non-cardiac Side Effects

• Most common: Nausea and vomiting due to GI irritation.
• Gynaecomastia: Displace testosterone from its receptor. 
• Hyperkalemia 
• Characteristics and specific visual abnormality: Yellow vision or Xanthopsia - Digoxin affects the Na⁺K⁺ channels on the retina.

Also read: Pharmacology Important Topics For NEET PG 2025

Cardiac Side Effects

• Most common: Ventricular premature beats (Bigeminy)
• Fatal: VF/VT
• Aggressive treatment: Class IB antiarrhythmic - Lignocaine > Phenytoin.
• Characteristic: Atrial fibrillation (Non-PSVT) + AV node block.
• Never causes Atrial flutter.

ECG Changes with Digoxin 

• ↑ PR Interval → AV node block
• ↑ RR Interval → SA node block
• Narrow QRS → Tells about Ven.depol - ↑ intracellular sodium.
• Inverted T wave → ¯ intracellular potassium.
• Reverse tick sign - Characteristic of digoxin toxicity. Also known as Salvador Dali sign → Digoxin intoxication.

Also read: Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Uses and Side Effects

Drug Interaction of Digoxin

Loop and thiazide:

• Increase Digoxin toxicity
• Reason: Hypokalemia

P-gp inhibitors

• Increase Digoxin toxicity
• Reason: Increase plasma digoxin (Not excreted via urine)
• Drugs
  • Verapamil
  • Amiodarone
  • Clarithromycin/Erythromycin
  • Ketoconazole

Cholestyramine and Antacids

• Reduce digoxin absorption from GIT, as it required bile for absorption

P-gp induces

• Reduces the effect of digoxin by increasing the excretion of digoxin in urine.
• Drug-Rifampicin

Also read: Pituitary Hypothalamic System in Pharmacology

Contraindications of Digoxin

Note- Mnemonic: HEART Will Cry

• High-output heart failure
• HOCM
• Electrolyte imbalances
  • Hypokalaemia (<3.5 mcg/dl)→Causes arrhythmias due to binding of digoxin to the heart muscle.
  • Hypercalcemia
  • Hypomagnesemia→ Leads to hypercalcemia
• AV node block
• Renal failure
• Thyroid abnormalities
  • Hyperthyroidism, which may lead to arrhythmias
• WPW syndrome
• Cardioversion

Wolff Parkinson White Treatment

• 1st: Radiofrequency ablation of abnormal pathways.
• If the patient is not eligible for surgery, then drugs are given.
• No structural heart disease DOC: Flecainide
• Structural heart disease—DOC: Procainamide

HOCM Treatment

• Reduce the contractility of the heart
• DOC: Beta-blockers, like atenolol and metoprolol.
• If asthma is present, DOC: CCB (Verapamil/Diltiazem)
• New drug-Mavacamten-Myosin inhibitor.
• Inhibit actin and myosin binding reduces contractility of the heart.

Also read: Anti-Dyslipidemic Drugs in Pharmacology

Download the PrepLadder app now to access high-yield content with 24-hr Free Trial. Explore premium study resources like Video Lectures also in हिंglish, digital notes, QBank, and Mock Tests for a seamless exam preparation. Time to begin your NEET PG coaching online with PrepLadder.