Cardiotonics (Cardiac Glycosides) 171
ECG changes: Digitalis, in therapeutic
doses causes inversion of T wave, sagging
of S-T segment and shortening of Q-T
internal (shortening of systole). In toxic dose,
it causes prolongation of P-R interval
(slowing of AV conduction), atrial
arrhythmias (atrial tachycardia and atrial
fibrillation) with AV block and ventricular
arrhythmias.
Extracardiac Actions
- Digitalis produces diuresis in CHF
patients, it increases excretion of
sodium and water by the kidney
which may be due to decrease in the
venous pressure bringing about
shifting of edema fluid into the
circulation and also improves the
renal circulation. - Digitalis can produce nausea and
vomiting which is probably due to the
chemoreceptor trigger zone (CTZ)
stimulation. - Digitalis has mild vasoconstrictor action
increasing the peripheral resistance. But
in CHF patients peripheral resistance
decreases due to withdrawal of reflex
sympathetic overactivity. Venous tone
improves in normal as well as CHF
patients. It has no significant effect on
coronary circulation.
Mechanism of Action of Digitalis
Digitalis acts by interfering with the
sodium and potassium transport across the
cell membrane and by increasing the
amount of coupling calcium i.e. making
more calcium available for excitation-
contraction coupling.
Cardiac glycosides inhibit Na+ K+-
ATPase by competing with potassium and
may probably explain reversal of toxic effects
of digitalis by potassium. Inhibition of the Na+
K+-ATPase leads to increase in intracellular
sodium and decrease in potassium.
Calcium also forms a link between the
electrical events in the membrane and
contractile proteins. Digitalis makes more
calcium available for excitation-contraction
coupling and increasing cardiac contractility.
Digitalis also exerts some indirect action
on heart mainly by increase in vagal activity
which ultimately influences activity of AV
node, SA node and auricles.
Pharmacokinetics
Among the cardiac glycosides, digitoxin is
absorbed rapidly and completely from the
gastrointestinal tract with oral absorption of
approximately 90 to 100 percent with plasma
protein binding of approx. 95 percent with
plasma half life of 5 to 7 days. It enters the liver
cells where it is metabolised to epidigitoxigenin
and is excreted in bile and urine.
Adverse Effects
It includes anorexia, vomiting which
may be of central origin. Headache, visual
disturbance, xanthopsia (yellow vision),
white vision, diplopia, drowsiness,
disorientation, delirium and psychotic
behaviour. Cardiac related effects include
cardiac arrhythmias e.g. tachyarrhythmias,
ventricular arrhythmias, supraventricular
arrhythmia, AV block and bradycardia.
Treatment of Digitalis Induced
Arrhythmias
Tachyarrhythmias
K+ tends to antagonise digitalis induced
enhanced automaticity and decreases bind-