Question 1

Classify commonly used inotropic agents. (40% of marks) Outline four different mechanisms of action for inotropic agents. (60% of marks) 

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College Answer

This question was generally well answered. The poorer answers suffered for want of a useful 
classification system that enabled them to separate the various drug classes.


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Classification of inotropes
Class Mechanism
Direct sympathomimetics
  • Endogenous
    • Adrenaline
    • Noradrenaline
    • Dopamine
  • Synthetic
    • Dobutamine 
  • Bind to beta-1 receptors
  • Activate G-protein coupled adenylyl cyclase
  • Increase cAMP production
  • This leads to increased calcium availability inside the cardiac myocytes, and therefore increased contractility and pacemaker automaticity
Indirect sympathomimetics
  • Ephedrine
  • Act as "false neurotransmitters"; displace catecholamines from presynaptic storage vesicles
  • The resulting catecholamine release produces direct catecholamine effects
Phosphodiesterase inhibitors
  • Milrinone
  • Inamrinone
  • Enoximone
  • Inhibit phosphodiesterase 3, which is responsible for cAMP catabolism.
  • Thus, increases cyclic AMP
  • Thus, increases calcium availability by increased voltage 
  • Selective for vascular smooth muscle and cardiac muscle.
Calcium sensitisers
  • Levosimendan
  • Pimobendan
  • Bind to troponin C and stabilise its open state
  • This allows muscle contraction.
  • Thus increased trop C / calcium complex stability increases contractility.
Cardiac glycosides
  • Digoxin
  • Inhibits Na+/K+ ATPase
  • Thus, increases intracellular sodium
  • This increases sodium-calcium exchange by the Na+/Ca2+ exchanger (INCX) during Phase 1 of the cardiac action potential.
  • The resulting increase in intracellular calcium promotes inotropy. 


Palmer, Kenneth, and Stephen H. Pennefather. "Inotropes." Anaesthesia & Intensive Care Medicine 10.8 (2009): 362-366.

Feldman, Arthur M. "Classification of positive inotropic agents." Journal of the American College of Cardiology 22.4 (1993): 1223-1227.

Jentzer, Jacob C., et al. "Pharmacotherapy update on the use of vasopressors and inotropes in the intensive care unit." Journal of cardiovascular pharmacology and therapeutics 20.3 (2015): 249-260.