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.

  • Question 13 from the second paper of 2008 (Levosimendan vs dobutamine)
  • Question 18 from the second paper of 2005 (noradrenaline, vasopressin and phenylephrine)
  • Question 9 from the first paper of 2004 (noradrenaline, vasopressin and phenylephrine)
  • Question 8 from the second paper of 2000 (dopamine and dobutamine.)

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.

A Comparison of Selected Inotropes

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; 
Half-life ~ 5 minutes
No active metabolites

Excreted into the small intestine
Slowly eliminated metabolites (half life ~ 80 hours)

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 chronotropy
Peripheral vasodilation (beta-2 effect of one of the enantimers)

Increased inotropy
Increased chronotropy
Increased lusitropy
Pulmonary vasodilation
Peripheral vasodilation (by action on ATP-sensitive potassium channels in vascular smooth muscle)

increases heart rate and contractility by increasing the intracellular levels of cAMP, thus increasing the availablility of intracellular calcium.

  • Low dose: increases renal blood flow
  • Medium dose: inotrope and chronotrope (beta
  • High dose: vasopressor
  • Beta1 effects: 2-10 mcg/kg/min
  • Alpha effects: >10 mcg/kg/min
  • Dopaminergic effects: 0.5-2 mcg/kg/min

Adverse effects

Arrhythmia
Hypotension
Increased cardiac metabolic demand, thus potentially exacerbating ischaemia   

Ventricular arrhythmias              

Arrhythmia
Hypotension

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

 

A Comparison of Selected Vasopressors

Features

Noradrenaline

Phenylephrine

Vasopressin

Class

Endogenous catecholamine

Phenylethylamine

Endocrine nonapeptide

Pharmacokinetics

Half-life 2-3minutes
Metabolised by MAO and COMT

Half-life 5-10 minutes

0.002 units /kg/min;

or, 2-2.4 units/hr

Receptor activity

Predominantly alpha-1 agonist activity;
Some beta-1 and beta-2 effects at high doses

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).
Some crossover with oxytocin with respect to uterine contraction.
Affinity for receptors is unchanged by acidosis

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.
V2 effect is via Gs-protein coupled receptors, and cAMP.

Clinical effects

Arterial and venous vasoconstriction
Reflex bradycardia 
Increased afterload and preload

Arterial and venous vasoconstriction
Reflex bradycardia 
Increased afterload and preload

Arterial and venous vasoconstriction
Reflex bradycardia 
Increased afterload and preload 
Increased resoprtion of water in the cortical collecting duct

 

References

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.