Catecholamines

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Natural catecholamines
Adrenalin - Adrenaline.svg
adrenaline
Noradrenaline - Noradrenaline.svg
Norepinephrine
Dopamine - Dopamine.svg
Dopamine

Catecholamines (also catecholamines or pyrocatecholamines ) are a biologically and medically important group of chemical substances which includes dopamine and its derivatives . The name is a trivial name and is derived from the common molecular component pyrocatechol (1,2-dihydroxybenzene) and the amino group common to them . Catecholamines occur naturally, but are also produced artificially. The main natural catecholamines are dopamine, norepinephrine, and adrenaline . They act as transmitters of nerve impulses ( neurotransmitters ) in the central nervous system and vegetative nervous system and, among other things, contribute to the body's fight-or-flight response . Noradrenaline and adrenaline are also hormones . All three are also used as drugs . The artificially produced catecholamines isoprenaline , dobutamine , dopexamine and α-methylnoradrenaline are also therapeutically important . All catecholamines work through G-protein coupled receptors , either through adrenoceptors or dopamine receptors .

Research history

Catecholamines have a number of priorities in research. Adrenaline was the first hormone extracted from its endocrine gland , presented in its pure form, clarified in its structure including stereochemistry , and artificially synthesized. Besides acetylcholine, it was the first neurotransmitter to be discovered (in amphibians ). The catecholamines were the first neurotransmitters in the central nervous system whose pathways were made visible, for example by immunohistochemistry . During research on the effects of adrenaline (and glucagon ), cyclic adenosine monophosphate was discovered as a second messenger . The discovery of the G proteins followed . One adrenoceptor, namely the β 2 -adrenoceptor, was the first hormone or neurotransmitter receptor whose gene was cloned .

physiology

biosynthesis

Biosynthesis of catecholamines from L - tyrosine .

The biosynthesis of the body's own 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. It starts from the amino acid tyrosine , which is first converted to levodopa by means of the enzyme tyrosine hydroxylase . In the next step, levodopa is converted into dopamine with the help of the aromatic L-amino acid decarboxylase . This can be hydroxylated to noradrenaline by dopamine beta-hydroxylase . The optional final step, the methylation of noradrenaline to adrenaline, is catalyzed by phenylethanolamine-N-methyltransferase . Released catecholamines are inactivated by uptake in cells and subsequent re-storage or degradation by monoamine oxidase or catechol-O-methyltransferase , and presumably also by renalase .

Effects

Rough classification in the low and medium dose range:

adrenaline
increases blood pressure and heart rate .
Norepinephrine
mainly increases blood pressure, not so much heart rate.
Isoprenaline
mainly increases the heart rate, not so much the blood pressure.
Dopamine
increases muscle cramping ability (positive inotropic ).
Dobutamine
increases muscle cramping ability (positive inotropic).

Side effects

  • All of them lead to cardiac arrhythmias ( arrhythmogenic ) in higher doses .
  • All of them are toxic to the cardiovascular system in high doses (cardiotoxic).
  • In high doses, norepinephrine has a centralizing effect on the circulation.

Catecholamines in diagnostics

About 1% of the catecholamines noradrenaline and adrenaline released from the adrenal medulla and the sympathetic nerves are excreted unchanged in the urine . 80–85% of the catecholamine excretion takes place as vanillin-mandelic acid and approx. 15% as metanephrine .

If pheochromocytoma is suspected , the determination of free metanephrines in the urine is necessary, as these tumors usually produce large amounts of noradrenaline. The metanephrine is determined in the urine , which was collected over 24 hours. In addition, a determination is usually made in the blood serum .

Catecholamines in therapy

The catecholamines adrenaline , noradrenaline and dobutamine are also available as drugs. They are administered in intensive care and emergency medicine . Indications include cardiopulmonary resuscitation (reanimation), states of shock and severe allergic reactions .

Catecholamines are highly effective and are usually given intravenously . An alternative form of administration for resuscitation is the endotracheal administration of adrenaline . This is useful if an endotracheal tube but no intravenous access is available. The rate of absorption is comparable, but the dose must be adjusted. Endotracheal application is clearly inferior to intravenous application. The rate of resorption cannot be reliably determined, and deposits can form which, after spontaneous blood circulation has returned, lead to cardiac arrhythmias. In the 2005 guidelines of the ERC , endobronchial administration was therefore only recommended in exceptional cases (and not as a regular measure, as was previously the case). Since the Guidelines 2010, endotracheal administration is no longer recommended in the current guidelines. The onset of action is comparable to venous administration, but the duration and effective dose are difficult to control. Studies have shown that intraosseous vascular access is effective, easy to use and can often be established without complications. All common emergency medication can be applied via an intraosseous access.

When using catecholamines for circulatory stabilization in intensive care medicine, a very even supply into the body must be ensured, as otherwise considerable pressure and heart rate peaks or (if supply is interrupted) drops in blood pressure and heart rate can occur. The uniformly slow supply is usually carried out with syringe pumps . An invasive blood pressure measurement via an arterial access and ECG monitoring is essential, since these substances have a considerable arrhythmogenic potential (i.e. can trigger cardiac arrhythmias up to and including ventricular fibrillation ). Use can cause heart attacks and cerebral hemorrhage due to high blood pressure.

The effectiveness of catecholamines in cardiogenic shock has not yet been clearly proven. Otherwise, the use of catecholamines in intensive care medicine is mostly based on experience . There are no randomized comparative studies because the catecholamines were available before the criteria of scientific, evidence-based medicine were widely accepted and their use often appears to be the only way to ensure survival, which is why many types of studies are prohibited for ethical reasons .

Individual evidence

  1. Uni Heidelberg emergency script, p. 42 (PDF file; 750 kB).

literature

  • JW Daly, B. Witkop: Newer studies on centrally acting endogenous amines . In: Angewandte Chemie . tape 75 , no. 12 , 1963, pp. 552-572 , doi : 10.1002 / anie.19630751207 .

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