Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties
MIOZAC solution is a direct-acting inotropic agent whose primary activity consists of stimulation of the ß1 receptors of the heart, while it has relatively modest chronotropic, hypertensive, arrhythmogenic and vasodilatory effects.
Unlike dopamine, it does not induce endogenous norepinephrine secretion.
In laboratory animals, for a given inotropic effect, dobutamine causes a lower increase in heart rate and a lower decrease in peripheral vascular resistance than isoproterenol.

In patients with depressed cardiac function, both dobutamine and isoproterenol induce the same increase in cardiac output. The dobutamine increases the systolic output without significantly increasing heart rate (however, tachycardia has occasionally been observed). On the contrary, isoproterenol increases cardiac output essentially with an increase in heart rate, while systolic output varies little or decreases.

The differential pressure increases with dobutamine as a consequence of the increase in systolic output.
Dobutamine has a minimal effect on mean arterial pressure in normotensive patients, while in patients with low output syndrome the mean arterial pressure increases with the increasing of a cardiac output.

A facilitation of atrioventricular conduction has been observed in human electrophysiology studies and in patients with atrial fibrillation.

The systemic vascular resistance, after the administration of dobutamine, generally decreases. In some cases, it is possible to observe a minimal degree of vasoconstriction. Most dobutamine experiences have been carried out in a short term, up to a few hours.

In the limited number of patients who were studied for 24, 48 and 72 hours, in some of them the increase in cardiac output persisted, while in others it returned to baseline values.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

The start of the activity of MIOZAC solution occurs in one or two minutes: to obtain the maximum effect at a certain infusion frequency, on the other hand, it can take up to ten minutes. The plasma half-life of dobutamine in humans is two minutes. The main metabolic pathways are methylation and conjugation of the catechol group.

In human urine, the main excreted products consist of dobutamine and 3-0-methyldobutamine conjugates.
the 3-0-methyl derivative of dobutamine is inactive.

Changes in the synaptic concentrations of catecholamines using reserpine or tricyclic antidepressants do not alter the effects of dobutamine in animals, this indicates that the effects of dobutamine are not dependent on pre-synaptic mechanisms.