Catecholamine

Catecholamines, and catecholamines or Brenzcatechinamine, are a biologically and medically important group of substances, the 2 - includes (3,4- dihydroxyphenyl ) ethylamine = dopamine and its derivatives. The name is a common name and comes from the the substances common constituent of the molecule 1,2- dihydroxybenzene = catechol = English catechol and their common amino ago. Catecholamines occur in nature, but are also produced artificially. The most important natural substances are dopamine, norepinephrine and epinephrine. They are a part, hormones, neurotransmitters other hand, in the central nervous system and the autonomic nervous system. They are also used as drugs. Therapeutically important are also the artificially produced catecholamines isoprenaline, dobutamine, dopexamine and α -methyl noradrenaline. All catecholamines act via G- protein - coupled receptors, either adrenoceptors or dopamine receptors.

History of Research

The catecholamines are attributable to a number of priorities in research. Adrenaline was the first hormone that is extracted from its endocrine, purely illustrated, clarified in its structure including the stereochemistry and was artificially synthesized. It was also next to the acetylcholine neurotransmitter erstentdeckte ( in amphibians ). Catecholamines were the first neurotransmitter in the central nervous system, the webs were visualized for example by immunohistochemistry. In research on the effect of adrenaline ( and glucagon ), the cyclic adenosine monophosphate was discovered as a second messenger. This was followed by the detection of the G- proteins. A adrenergic receptor, namely, the β2 - adrenergic receptor, was the first neurotransmitter or hormone receptor, its gene was cloned.

Physiology

Biosynthesis

The biosynthesis of endogenous catecholamines was elucidated in 1939 by the German pharmacologist Peter Holtz and the German -British pharmacologist Hermann Blaschko. It takes place in the adrenal medulla and the " catecholaminergic " nerve cells instead. It starts from the amino acid tyrosine, which is first converted to levodopa by the enzyme tyrosine hydroxylase. The next step is formed of levodopa by using the aromatic -L- amino acid decarboxylase dopamine. This can be hydroxylated by the dopamine -beta- hydroxylase to noradrenaline. The optional final step, the methylation of norepinephrine to epinephrine, catalyzes the phenylethanolamine N- methyltransferase. Released catecholamines are inactivated by uptake into cells and subsequent re- storage or degradation by monoamine oxidase or catechol-O- methyltransferase.

Effects

• Rough classification in the low and mid dose range: adrenaline increases blood pressure and heart rate.

• Increases, especially blood pressure, not so much the heart rate.

• Increases especially the heart rate, not so much the blood pressure.

• Positive inotropic

• Positive inotropic

Side effects

• All are arrhythmogenic in higher dose;

Catecholamines in the diagnosis

The released from the adrenal medulla and sympathetic nerves from the catecholamines norepinephrine and epinephrine are secreted to about 1% unchanged in the urine. 80-85% of the catecholamine done as vanillylmandelic acid and about 15% as metanephrines.

In cases of suspected pheochromocytoma the determination of free metanephrines in the urine is necessary, since these tumors usually produce large amounts of noradrenaline. Determining the Metanephrine takes place in the urine was collected over 24 hours. In addition, usually a determination is made in the blood serum.

Catecholamines in therapy

Catecholamines are also available as medications available as epinephrine, norepinephrine, dobutamine. They are administered in the intensive care and emergency medicine. Indications include cardiopulmonary resuscitation ( CPR ), shock states and severe allergic reactions.

Catecholamines are highly effective and are usually given intravenously. An alternative form of administration during resuscitation, the endotracheal administration of epinephrine dar. This is useful when an endotracheal tube, but no intravenous access is available. The rate of absorption is comparable, but the dose should be adjusted. Endotracheal application is clearly inferior to intravenous. Thus, the rate of absorption can not be reliably determined, it can come to Depot formations that lead to the return of spontaneous circulation or cardiac arrhythmia. In the 2005 guidelines of the ERC therefore endobronchial administration was recommended only in exceptional cases (and not as in the past as a control measure). Since the Guidelines 2010, the endotracheal administration in the current guidelines is no longer recommended. The onset of action is indeed comparable to the venous administration, however, duration of action and effective dose are difficult to control. Studies have shown that the intraosseous vascular access is effective in handling simple and often to establish without complications. All common emergency drugs can be administered via an intraosseous access.

When Katecholaminanwendung for hemodynamic stabilization in the ICU is to pay attention to a very uniform supply in the body, as otherwise considerable pressure and heart rate spikes, or ( in case of interruption of supply ) can blood pressure and heart rate drops occur. The uniformly slow feed is usually carried out with syringe pumps. An invasive blood pressure measurement via an arterial access and ECG monitoring is essential, since these materials have a significant arrhythmogenic potential ( ie can cause heart rhythm disorders and even ventricular fibrillation). In the application may lead to heart attacks and cerebral hemorrhage due to high blood pressure.

The effectiveness of the catecholamines in cardiogenic shock is not clearly documented until now. Even otherwise, the use of catecholamines in critical care is usually based on empirical experience. Randomized comparative studies are scarce because the catecholamines were faced with the widespread acceptance of the criteria of "evidence based medicine " are available and their use is often the only way to maintain compatible with the survival of circulatory situation so that prohibit comparative studies with placebo for ethical reasons.