1. Positive inotropes improve cardiac function by a number of mechanisms, which usually result in increased intracellular calcium. Xenobiotics that [1] increase cAMP: Glucagon receptors and β-adrenergic receptors are coupled to GS proteins so that receptor binding increases cAMP by activation of adenyl cyclase. Phosphodiesterase inhibitors increase cAMP by inhibiting its breakdown. [2] increase calcium influx: Calcium salts increase calcium influx through L-type calcium channels by a direct mass effect. [3] inhibit extrusion of calcium via the sodium-calcium exchange pump: Those that increase intracellular sodium such as digoxin and sodium channel agonists (eg, aconitine) and those such as 4-aminopyridine that prolong the action potential duration alter the electrochemical gradients in a way that hinders the extrusion of calcium. [4] increase the sensitivity of the contractile elements to calcium: Angiotensin II and endothelin do this by inducing an intracellular alkalosis. The calcium sensitizers, levosimendan and pimobendan are used to treat heart failure in some countries.
Source: Cardiopulmonary Medications, Goldfrank's Toxicologic Emergencies, 10e
Citation: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank's Toxicologic Emergencies, 10e; 2015 Available at: Accessed: October 25, 2017
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