Term 1 Pharm - Digoxin

Question 1

What plant does Digoxin come from and what else has the plant been used for?

Answer 1

Foxglove

Dropsy, Ascites/Anasarca → usually result of forward & backward failure

Question 2

Pharmacodynamics of digoxin

Answer 2

Inotropic effects (increase myocardial contractility)

1. Primary action: inhibits the Na, K-ATPase enzyme/pump in cell membrane. Which leads to more sodium inside the cell, and less potassium pumped into the cell
2. This inhibition serves to increase the intensity of interaction of actin and myosin filaments in the sarcomere
3. How? By increasing intracellular [Ca++] near these proteins

“anti-arrhythmic effects”

1. Primary action is to slow conduction through the AV node (vagotonic effect) – by increasing vagal tone → used for Afib… Digoxin can be used for Afib but not a 1st choice (adverse effects), use beta blocker/Ca blocker instead
2. Useful in slowing ventricular response rate to atrial fibrillation
3. Not very good at converting AF to NSR, nor useful for other arrhythmias
4. Can have pro-arrhythmogenic effects as well!!!

*Use in CHF with normal sinus rhythm (especially if dilated left ventricle present)
*Use in patients with atrial fibrillation to slow AV conduction (“rate control”)
NEVER been shown to prolong survival

Question 3

Adverse side effects from digoxin…

Answer 3

Interactions with other drugs (many drug- drug interactions with digoxin) a few important examples:

1. Absorption reduced by oral antacids (e.g. Mg, Al hydroxides)
2. *Quinidine (reduces renal clearance of digoxin by about 50%!!!) → should give half dose
3. Amiodarone (additive effects on A-V node conduction)
4. Verapamil, propranolol (additive effects on A-V node conduction) → can produce heart block

*Excreted mainly by kidney, renal failure → toxic side effects from normal drug dose

Question 4

2. Absolute contraindications of digoxin

Answer 4

• Ventricular tachycardia, VF (may cause or worsen)
• Wolff-Parkinson-White syndrome (may encourage conduction down accessory pathway, not good!!!)
• 1st, 2nd and 3rd degree AV or SA block (may worsen any AV block)
• HOCM (IHSS) (may worsen degree of functional obstruction).

Question 5

DIGOXIN (LanoxinTM)

Answer 5

Drug class: most common member from class called digitalis glycosides (also contains digitoxin); considered both an antiarrhythmic agent and an inotropic agent

Pharmacodynamics: therapeutic levels cause a vagotonic effect that is useful in slowing AV conduction in patients with atrial fibrillation; “rate control”; toxic levels increase automaticity of all areas of the heart except the SA node; increase Ca++ flux into sarcomere increasing inotropy

Pharmacokinetics: bioavailability 60-95% (best with capsule); can be given slowly IV; redistribution over about 8 hours; clearance 80% renal, t1/2 30-40 hours (with normal GFR); markedly high Vd (approx. 6-7 L/kg).

Toxicity (contraindications, precautions, ADRs): contraindicated in patients with VF, hypertrophic cardiomyopathy (IHSS), AV block, WPW syndrome, sinus node disease, hypoxia; common ADRs nausea, vomiting, visual changes, agitation or nightmares, increased automaticity, AV block.

Interactions with other drugs: antacids (decreased absorption), quinidine (decreased renal clearance, increases Cpss about two-fold)), other drugs with additive effects on AV nodal conduction.

Special considerations: WATCH OUT WHEN patients have renal failure; starting quinidine; hold prior to cardioversion.

*generic form of digoxin is very inexpensive