Core pharmacology

Mechanism of action

i) Na/K ATPase inhibition → ↑ intracell Na → ↓ Na-Ca pump → ↑ intracell Ca → inotropy
ii) direct: ↑ AV node ERP, ↓ V ERP
iii) Indirect: Via Vagus – bradycardia, ↓ A refr. Augmentn of direct ↑ AV node ERP

Onset Peak Duration

onset / duration Oral: 1-2 hours; I.V.: 5-60 mins / 3-4 days

Absorption

IV, PO BA 60-80%

Protein binding

prot bind ~25%; uremia- displaced fm pl prot bind sites

Volume of distribution

6-7 L/kg
thyroid (↑ in hyper, ↓ hypo).

Metabolism

Stomach:Sequential sugar hydrolysis+ redn of lactone ring by intestinal bacteria
min hepatic, most excr unchanged

Excretion

Urine (50% to 70% unchanged)

Half-life

36-48 hours

Physiological effects

Positive inotropy. Slows sinus rate and AV-nodal conduction and increases AV-nodal refractoriness through direct electrophysiological and vagotonic effects. Rapid IV administration may cause vasoconstriction. Characteristic ECG effects include PR prolongation, ST depression, T-wave flattening and QT shortening. Mild diuresis.