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

i) ↑myofilament Ca sensitivity by binding to Cardiac trop C in Ca-dependent manner.
ii) Vasodilation through opening of ATP-sensitive K channels
iii) selective PDE-III inhibition at higher conc - inotropy

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.

Effects: Inotropy
Direct and indirect effects on refractory period + bradycardia -> treat AF&flutter

CVS
- The main action of digoxin is to increase the force of cardiac contraction; automaticity and contractility also increase.
- The heart rate is slowed due to a combination of improved haemodynamics, depression of sinus node discharge, slowing of AV nodal conduction, an increase in the AV nodal refractory period, and an indirect vagotonic effect.
- Rapid intravenous administration of digoxin may cause vasoconstriction, leading to hypertension and decreased coronary blood flow.
- The characteristic ECG changes produced by the drug include prolongation of the PR interval, ST-segment depression, T-wave flattening, and shortening of the QT interval

GIT - Anorexia/N/V/Diarrhoea (especially if therapeutic range exceeded)

CNS
- Headache, confusion, coma (toxicity)
- Visual disturbances (deranged red-green colour perception)

Renal- Mild diuretic effect

Miscellaneous- Rashes, eosinophilia; Gynaecomastia

CVS:
- Increased cardiac output without increasing MVO2
- Causes coronary and peripheral vasodilation → anti-ischaemia and anti-stunning effects

GU:
Increased GFR and UO secondary to increased CO

IV, PO BA 60-80%

IV only

small vd

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

98% protein binding.
Peak concentration after 48 hrs

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

0.2 L/kg

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

Intestinal bacteria OR1896 active metabolite

Hepatic conjugation

Urine (50% to 70% unchanged)

excretion renal and fecal. Cardiac Effects 2-7 days

36-48 hours

1 hour (70hr for active metabolite)

Thyroid-Vd
Narrow therapeutic window -monitoring - 0.5-2mcg/L(~1)
Toxic > 2.5- arrhythmias, AV block.
anorexia,N/V/D, lethargy. Altered Red green colour perception. ECG: ↑ PR, ST dep, T fl-attening, ↓QT. (may not indicate toxicity)

Interference with potassium channels causes an increase in the QTc- theoretical ↑risk of arrhythmias. May cause hypotension. Caution should be exercised in
patients with renal or hepatic impairment.

Antiarrhythmic –
Vaughan Williams Class V
Other

NON-ADRENERGIC

used in AF and atrial flutter, SVT and in heart failure

short term management of severe acute heart failure

glycoside derived from the dried leaves of the foxglove

Block Na-K-ATPase pump

Ca sensitizer and PDE-III inhibitor
selectively

Level 1

Level 3

Level 3

Level 1

Increases Myofilament Ca sensitivity, vasodilation

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

PO: tablets 62.5mcg or 250mcg. IV:25-250mcg/ml.
Narrow therapeutic window. Monitoring necessary - 0.5-2mcg/L(~1)

in IV form only - clear yellow solution 2.5mg/mL in 5 and 10ml vials

IV/PO.
loading 250-500mcg QID then 62.5-125mcg daily

IV, loading dose of 6 to 24 mcg/kg over 10 minutes
then continuous infusion of 0.05-0.2 mcg/kg/min