The following is directly taken from"Cadioactive Drugs A Pharmacologic Basis for Practice" by Hansjorg Simon and Dennis A. Bloomfield.

Some of the most important factors that can modify the effect of glycosides on the electrophysiological processes at the myocardial cell are extracellular potassium and calcium concentration, partial oxygen pressure, blood pH, and the autonomic nervous system.

Increase of extracellular potassium inhibits automaticity and suppresses the activity of ectopic centers. Correspondingly, the opposite effect is produced by decrease of extracellular potassium, e.g., through diuretic therapy. The influence of potassium on the atrioventricular node is complex, because low as well as high potassium concentrations inhibit atrioventricular transmission.

To a great exent, calcium and glycosides act synergistically. If serum calcium is low, glycosides can no longer effect the same increase in contractility as with normal calcium levels. Hypercalcemia enhances the tendency to ectopic stimuli formation in glycoside medication.

Partial pressure of oxygen
Hypoxia shortens the effective refractory period of the ventricles and probably promotes automaticity. This explains the tendency to ectopic beats when hypoxia supervens on glycoside therapy.

pH value Modification of glycoside action through pH changes is a consequence of its influence on potassium and calcium distribution. Acidosis leads to decrease of intracellular and increase of extracellulsr potassium.

Autonomic nervous system
The influence of the autonomic nervous system on the effect of glycosides is very complex.
1) Part of the glycoside effect is exerted through cholinergic influences.
2) An antiadrenergic effect of glycosides on sinus and atrioventricular nodes is known.
3. Part of the glycoside effect on secondary pacemaker cells may be the effect by adrenergic transmitter substances.
4. Cancellation on this effect can be successfully achieved with beta-blockers, reserpine, or potassium.
5. Influence on contractility is independent of cholinergic or adrenergic transmission.

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