The college has historically asked a series of questions comparing vasopressors and inotropes to one another, presumably to see who among the trainees could explain why they use vasopressin and not phenylephrine (for example). So far, the drugs discussed in such question have been limited to levosimendan, dobutamine, noradrenaline, phenylephrine, vasopressin and dopamine. Of these questions, none have been repeated since 2008, suggesting that the college have decided to stop putting them into the fellowship papers. Some might argue that pharmacokinetics and pharmacodynamics belong in the primary exam, and the fellows should be busy analysing the published evidence of efficacy, clinical trials and suchlike. Other might point out that most of the evidence generated by ICU studies is negative or inconclusive, and that the application of basic sciences still determines much of what happens with ICU drugs.
In each of the above, a tabulated comparison is available. In order to simplify revision, all those tables were concocted into the summary offered below. Additionally, detailed monographs on some of these drugs are available in the "Fluid Resuscitation, Vasopressors and Inotropes" section of this site.
In the context of pre-exam revision, these probably represent a pointless digression.
Features |
Dobutamine |
Levosimendan |
Dopamine |
Class of drug |
Synthetic catecholamine |
Calcium sensitizer |
Endogenous catecholamine |
Administration |
IV infusion 5-15mcg/kg/min |
IV infusion 0.05-0.2mcg/kg/min |
1-5 mcg/kg/min IV (low dose) 5-15 mcg/kg/min IV (medium dose) 20-50 mcg/kg/min IV (high dose) |
Pharmacokinetics |
Rapidly metabolised by COMT; |
Excreted into the small intestine |
Half-life 2-3minutes Metabolised by MAO and COMT |
Mechanism of action |
Activates beta-1 adrencoeptors and increases heart rate and contractility by increasing the intracellular levels of cAMP, thus increasing the availablility of intracellular calcium. |
Enhances the affinity of contractile proteins (partiularly cardiac troponin C) for calcium, thereby increasing contractility without incurring additional ATP cost |
Predominantly beta-1 receptor agonist at low doses, with more alpha-effects as dose escalates D-1 receptor agonist at low doses |
Clinical effects |
Increased inotoropy |
Increased inotropy |
increases heart rate and contractility by increasing the intracellular levels of cAMP, thus increasing the availablility of intracellular calcium.
|
Adverse effects |
Arrhythmia Ventricular arrhythmias |
Arrhythmia Ventricular arrhythmias |
Arrhythmogenic at the high doses required for treatment of severe sepsis Increased cardiac oxygen demand due to increased contractility and heart rate may cause ischaemic phenomena No evidence for any renal protective effects |
Features |
Noradrenaline |
Phenylephrine |
Vasopressin |
Class |
Endogenous catecholamine |
Phenylethylamine |
Endocrine nonapeptide |
Pharmacokinetics |
Half-life 2-3minutes |
Half-life 5-10 minutes |
0.002 units /kg/min; or, 2-2.4 units/hr |
Receptor activity |
Predominantly alpha-1 agonist activity; Affinity for receptors decreases in acidosis |
Strongly selective for alpha-1 receptors Affinity for receptors decreases in acidosis |
Acts on V1 receptors (for vasopressor activity) and on V2 receptors (for antidiuretic activity). |
Mechanism |
Increases intracellular IP3, which in turn increases the availablility of intracellualr calcium to smooth muscle contractile proteins |
Increases intracellular IP3, which in turn increases the availablility of intracellualr calcium to smooth muscle contractile proteins |
V1 effect is by Gq-protein coupled receptors, which also increases intracellular IP3. |
Clinical effects |
Arterial and venous vasoconstriction |
Arterial and venous vasoconstriction |
Arterial and venous vasoconstriction |
Goldberg, L. L. "Dopamine: Clinical uses of an endogenous catecholamine." New England Journal of Medicine 291.11 (1974): 707-10.
Holmes, Cheryl L., Donald W. Landry, and John T. Granton. "Science review: Vasopressin and the cardiovascular system part 1–receptor physiology." Critical care 7.6 (2003): 427.
Holmes, Cheryl L., Donald W. Landry, and John T. Granton. "Science Review: Vasopressin and the cardiovascular system part 2-clinical physiology." CRITICAL CARE-LONDON- 8.1 (2004): 15-24.