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2 Cards in this Set
Inhibition of Na+/K+ ATPase of the cell membrane by digitalis is well documented and is considered to be the primary biochemical mechanism of action (Figure 13–3). Inhibition of Na+/K+ ATPase results in a small increase in intracellular sodium. The increased sodium alters the driving force for sodium-calcium exchange by the exchanger, NCX, so that less calcium is removed from the cell. The increased intracellular calcium is stored in the sarcoplasmic reticulum and upon release increases contractile force.
These drugs increase cyclic adenosine monophosphate (cAMP) by inhibiting its breakdown by phosphodiesterase and cause an increase in cardiac intracellular calcium similar to that produced by -adrenoceptor agonists. Phosphodiesterase inhibitors also cause vasodilation, which may be responsible for a major part of their beneficial effect. At sufficiently high concentrations, these agents may increase the sensitivity of the contractile protein system to calcium