cAMP-Elevating Agents

cAMP-ELEVATING AGENTS

The immediate effect of increasing intracellular cAMP levels is an increase in contractility. This has been ob-served repeatedly in acutely ill patients in the intensive care unit with the intravenous infusion of either β-adrenergic agonists (e.g., dobutamine) or the phos-phodiesterase inhibitors milrinone (Corotrope) and am-rinone (Inocor). Binding of dobutamine to cardiac myo-cyte adrenoceptors results in G-protein coupling, activation of adenylyl cyclase, and the conversion of ATP to cAMP.

Administration of either milrinone or amrinone in-creases cAMP levels by preventing its degradation by cardiac myocyte phosphodiesterases. Both classes of cAMP-elevating agents have been shown to be helpful for the acute short-term management of the decompen-sated patient. Unfortunately, the long-term continuous use of either of these classes of agents in the outpatient setting has been associated with an increase in mortal-ity in CHF. However, the use of these drugs in appro-priately selected patients is highly effective for sympto-matic relief.