Inotropes

Inotropes increase the force of contraction of cardiac muscle and thereby increase cardiac output. In general, they are used to prevent anaerobic metabolism by improving oxygen delivery to the tissues. Inotropic agents have varying pharmacological profiles; drug selection according to the clinical circumstance enables benefits to be maximized while minimizing side effects. Most inotropes act to increase intracellular calcium levels. Adrenoceptor agonists (e.g. epinephrine) achieve this by activating adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) levels and protein kinase activity, which potentiates the opening of voltage-gated calcium channels and increases the amount of calcium released from the sarcoplasmic reticulum. Phosphodiesterase inhibitors (e.g. milrinone) block the degradation of cAMP, thereby increasing protein kinase activity and calcium levels. Raised intracellular calcium is, however, associated with arrhythmias and cell death, leading to the development of newer agents that act by different mechanisms. Levosimendan improves the sensitivity of the contractile apparatus to calcium, thereby increasing inotropy. Epinephrine remains the drug of choice in emergencies (cardiac arrest, anaphylaxis). Inotropes are commonly administered by controlled infusion in the critical care environment, to allow close monitoring and careful titration. The combined use of several inotropes in lower doses may confer a benefit over single agents used at high doses.