25A09: Exam Report
Compare and contrast milrinone and dobutamine using the following headings:
- Class and indications for use (20% of marks).
- Mechanisms of action (20% of marks).
- Pharmacodynamics and adverse effects (60% of marks).
66% of candidates passed this question.
High performing answers were structured according to the headings provided and used tables.
They emphasised the shared features of milrinone and dobutamine under each heading, but also clearly pointed out the important differences and why they matter. Some candidates were unable to obtain sufficient marks as entire section/s of the answer were omitted.
Milrinone & dobutamine are both level one medications in the syllabus and thus a detailed working knowledge of all content asked in the question was expected.
G7i / 25A09: Compare and contrast milrinone and dobutamine
- Interestingly, Dobutamine is listed as a level one drug when in fact the syllabus states it is a level three drug. (as Jenny says, all drugs are Level 1 – don’t kid yourself)
- Dobutamine is a racemic mixture. The dextro (+) isomer is the potent beta1 agonist and the levo (-) is a partial alpha1 agonist. This was not included given it was not asked explicitly in the question.
a) Class and Indication for use
Milrinone
Dobutamine
Class
Milrinone
- Bipyridine molecule
- Inodilator
- Non-adrenergic inotrope
- Synthetic
Dobutamine
- Synthetic isoprenaline derivative
- Synthetic catecholamine
- Positive inotrope
Indication
Milrinone
- Acute management of severe cardiac failure
- Low cardiac output states following cardiac surgery
- Right Heart Failure
Dobutamine
Inotropic support in those with low CO secondary to:
- MI
- Post cardiac surgery
- cardiomyopathy
- septic cardiomyopathy
- cardiac stress testing
Dobutamine, which is a Beta-1 selective adrenergic agonist.
b) Mechanism of Action
Mechanism of Action
Milrinone
- Selective PDE III inhibitor in cardiac and vascular smooth muscle
- Decreased cAMP breakdown in heart → PKA activation → downstream increase in intracellular calcium → positive inotropy → increased SV → Increased CO
- Decreased cAMP breakdown in VSMC → cAMP-dependent INHIBITION of MLCK (myosin light chain kinase) → decreased phosphorylation of MLC (myosin light chain) → vaso smooth muscle relaxation → vasodilation.
Dobutamine
- Positive inotrope via β1 selective agonism
- Beta 1 agonism → Gs g protein → AC activation → cAMP (from ATP) via AC → PKA activation → increased Ca++ in cell via influx→ increased inotropy → increased SV → increased CO.
- β₁ > β₂ >>>> α
c) Pharmacodynamics and adverse effects
Pharmacodynamics
CVS
Milrinone
- Positive inotropy = increase in CO
- Decrease in pulmonary capillary wedge pressure
- Minimal effects on HR and myocardial O2 consumption
- Vasodilation = decreased SVR = decreased MAP (hence inodilator)
Dobutamine
- Increased inotropy, chronotropy, dromotropy.
- Increased MAP
- Increased myocardial O2 consumption (unlike milrinone)
- Mild effect on SVR due to alpha 1 and beta 2 agonism. Overall mild decrease in SVR.
- Decreased LVEDP and SVR improve CI in severe CHF.
Renal
Milrinone
- Increase in UO and GFR due to increase in CO and renal perfusion.
Dobutamine
- Increased UO secondary to an increase in CO
CNS
Milrinone
–
Dobutamine
- Stimulation at high doses
Metabolic / other:
Milrinone
–
Dobutamine
- Enhances NK cells
- Decreased BSL and free fatty acid concentrations
Adverse Effects
Milrinone
- Ventricular ectopics
- Arrhythmia (secondary to increased AV nodal conductance)
- Hypotension (from decreased SVR. May need to start a vasopressor like noradrenaline)
Dobutamine
- Usually above 10mcg/kg/min
- Arrythmias
- Excessive tachycardia
- HTN
- Nervousness
- Chest pain
- Allergy (rare)
- Avoid in cardiac outflow obstruction (AS, tamponade)
- Tachyphylaxis can occur in prolonged infusion.
Sources:
- Drugs in Anaesthesia and Intensive Care (Scarth, Smith)
- Katzung Pharmacology (16th Edition)
Author: Alex Fagarasan