Which enzyme metabolizes dobutamine

The response of dobutamine concentration to an infusion of dobutamine is rather predictable, even in patients with severe heart failure. The rate of clearance is non-saturable, and so as you increase the infusion rate, so the concentration increases. Furthermore, the onset of its effect is so rapid that no loading dose is necessary, and an infusion reaches its plateau effect within 10 minutes or so. As for the metabolic pathway Dog data again?

Oh well. It seems in the puppies, the major circulating end-product is the glucouronide of 3-O-methyldobutamine. The glucouronide is predictably inactive; however, there is good in-vitro evidence that while it waits to be conjugated, the 3-O-methyldobutamine actually has a potent alpha-antagonist effect at least in vitro , which sounds pretty counterproductive.

This, of course, complicates the already complex relationship of dobutamine to its effects: not only must we deal with two stereoisomers which have different sympathetic effects, and inhibit each other , but there is a potentially active metabolite with a longer halflife. Beta-1 activity can be summarized as the activation of cyclic AMP in the myocytes, resulting in increased L-type voltage gated calcium channel availability at the membrane.

This means, every depolarization is met with more intracellular calcium, and thus increased contractility. However, this is the beta-1 effect alone. But we recognise that dobutamine is a dirty racemic whore, with many sly effects; all adrenoceptors are somehow tickled by this molecule. The alpha-1 receptor pathways already receive sufficient attention in the discussion of noradrenaline, and will not be revisited here.

In order to get one's head around the effects of dobutamine as a racemic mixture, one ought to consider the effects of each stereoisomer independently. One article , sadly without a full-text option, discusses these effects in exhausting detail. The below table summarises the effects of the stereoisomers and their racemate. Rober R Ruffolo seems to have sacrificed more rats to the study of dobutamine than any other investigator, and I take my hat off to his many works on this subject.

Let us reap their reward. However, by binding to and not activating the alpha-1 receptors, it acts as a full alpha-1 antagonist. Used in isolation, it reduces peripheral vascular resistance and increases heart rate - but, curiously, it does not do much for the stroke volume.

The increase in cardiac output is modest, and mediated purely by the increase in heart rate. The - stereoisomer possesses mainly alpha-1 activity, but it is only a partial agonist. Used in isolation, it barely touches heart rate - but it increases mean arterial pressure, and causes a nice increase in stroke volume, which is generally thought to be mediated by myocardial alpha-1 receptor stimulation. Enraged by biochemical pedantry, the pragmatic intensivist will bellow "Who cares about this bullshit!

What are the haemodynamic effects of the racemate? No company makes available an isolated stereoisomer. This is because apart they are feeble, but together they create a potent inotrope.

In combination, the vasoconstricting and vasodilating effects cancel each other out, and what one is left with is the alpha-1 mediated increase in stroke volume, and beta-1 mediated increase in heart rate, with the resulting increase in cardiac output. Let us examine the seminal paper on dobutamine , to witness its dose-response relationship.

This helpfully free-to-read article from presents beautiful graphs to illustrate the effects of increasing dobutamine doses on blood pressure, heart rate and myocardial contractility. However, because there is such a wide variability in response among the critically ill patients, some titration does occur; however it is a slow process, because the real titrated variable is cardiac output, which is not a conveniently available parameter; furthermore one's endpoints are not a numerical value of the cardiac index, but rather the improvement in end-organ perfusion, which takes a little while to manifest.

For this reason, one's rate of infusion tends to remain fixed for periods. Note that no marked vasopressor or vasodilator activity occurs. The mean arterial pressure does not vary greatly over the range of doses. This is also observed in a realistic setting, when dobutamine is used in cardiogenic shock.

The BMJ published a nice study in , where the haemodynamic effects of dobutamine were compared to those of salbutamol weirdly, the two drugs have very similar haemodynamic effects, which suggests that one can "cheat" with nebulised salbutamol. In spite of a rather dramatic fall in systemic vascular resistance, the investigators found that the MAP remained much unchanged with these patients, as the heart rate and stroke volume maintained cardiac output. This, though encouraging, is obviously dependent on how much contractility one can wring out of a struggling infarcted myocardium.

Let us say there is a point - some arbitrary point in the dose range, different for each patient- at which the contractility improvement will plateau. Beyond such a point, one's cardiac index will no longer improve with increasing dobutamine doses. The K i for dopamine as an inhibitor of dobutamine methylation was 1.

Dopamine but not dobutamine was a substrate for MAO. It is a beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery.

Belongs to the class of organic compounds known as catecholamines and derivatives. Catecholamines and derivatives are compounds containing 4- 2-Aminoethyl pyrocatechol [4- 2-aminoethyl benzene-1,2-diol] or a derivative thereof formed by substitution. Organic compounds. Catecholamines and derivatives. Phenethylamines Aralkylamines 1-hydroxyunsubstituted benzenoids 1-hydroxyunsubstituted benzenoids Dialkylamines Organopnictogen compounds Organooxygen compounds Hydrocarbon derivatives.

Catecholamine Phenethylamine 1-hydroxyunsubstituted benzenoid 1-hydroxyunsubstituted benzenoid Aralkylamine Monocyclic benzene moiety Secondary aliphatic amine Secondary amine Organopnictogen compound Organooxygen compound Organonitrogen compound Amine Organic oxygen compound Organic nitrogen compound Hydrocarbon derivative Aromatic homomonocyclic compound.

Naturally occurring process Biological process Biochemical pathway Drug action pathway Dobutamine action pathway. Calcium handling is an important determinant of myocardial oxygen consumption. Therefore, we hypothesized that this phenomenon was due to reduced myofilament responsiveness to calcium, related to protein kinase C activation.