Dopamine
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Dopamine

Dopamine is a chemical naturally produced in the body. In the brain, dopamine functions as a neurotransmitter, activating dopamine receptors. Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary. more...

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Dopamine can be supplied as a medication that acts on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. However, since dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. To increase the amount of dopamine in the brain of patients with diseases such as Parkinson's disease and Dopa-Responsive Dystonia, a synthetic precursor to dopamine such as L-DOPA can be given, since this will cross the blood-brain barrier.

Biochemistry

Dopamine has the chemical formula (C6H3(OH)2-CH2-CH2-NH2). Its chemical name is 4-(2-aminoethyl)benzene-1,2-diol and it is abbreviated "DA."

As a member of the catecholamine family, dopamine is a precursor to epinephrine (adrenaline) and norepinephrine (noradrenaline) in the biosynthetic pathways for these neurotransmitters. Arvid Carlsson won a share of the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not just a precursor to these, but a neurotransmitter as well.

Dopamine is synthesized in the body (mainly by nervous tissue and adrenal glands) first by the dehydration of the amino acid tyrosine to DOPA by tyrosine hydroxylase and then by the decarboxylation of DOPA by aromatic-L-amino-acid decarboxylase. In neurons, dopamine is packaged after synthesis into vesicles, which are then released in response to the presynaptic action potential. The inactivation mechanism of neurotransmission are 1) uptake via a specific transporter; 2) enzymatic breakdown; and 3) diffusion. Uptake back to the presynaptic neuron via the dopamine transporter is the major role in the inactivation of dopamine neurotransmission. The recycled dopamine will face either breakdown by an enzyme or be re-packaged into vesicles and reused.

Functions of dopamine in the brain

Role in movement

Dopamine is critical to the way the brain controls our movements and is a crucial part of the basal ganglia motor loop. Shortage of dopamine, particularly the death of dopamine neurons in the nigrostriatal pathway, causes Parkinson's disease, in which a person loses the ability to execute smooth, controlled movements.

Role in cognition and frontal cortex function

In the frontal lobes, dopamine controls the flow of information from other areas of the brain. Dopamine disorders in this region of the brain can cause a decline in neurocognitive functions, especially memory, attention and problem-solving. Reduced dopamine concentrations in the prefrontal cortex are thought to contribute to attention deficit disorder and negative schizophrenia.

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The safety of dopamine versus norepinephrine as vasopressor therapy in septic shock
From CHEST, 10/1/05 by Jaime J. Simon Grahe

PURPOSE: We evaluated a strategy of dopamine (DA) vs norepinephrine (NE) as the primary vasopressor support in patients with septic shock. Concern for potential adverse events or a significant improvement in outcome prompted an interim safety analysis after approximately 50% of the target subjects were enrolled.

METHODS: MICU patients with septic shock were prospectively randomized to receive either DA or NE as the first-line vasopressor. All patients were treated with early-goal directed medical therapy including luid resuscitation, antibiotics, tight glycemic control and management of adrenal insufficiency, as appropriate. A protocol governed the titration of vasopressors to achieve a mean arterial pressure (MAP) of > 60mmHg or systolic blood pressure (SBP) > 90mmHg. After the maximum dose of either DA or NE was reached, patients received vasopressin at a fixed dose of 0.04 units/minute, followed by titration of phenylephrine to maintain the bloodpressure goal. An interim analysis was performed to evaluate safety and efficacy of each vasopressor.

RESULTS: Sixty-six patients, 35 DA and 31 NE, have been enrolled in the study. APACHE II scores, gender, and age were all similar at baseline between the two groups. There was no significant difference in mortality comparing the two groups (DA 40%, NE 41.8%). Cardiac dysrhythmias occurred in 31.4% of the DA group compared to 3.2% for NE (p=0.003). All cardiac dysrhythmias required an intervention.

CONCLUSION: There was a significant increase in cardiac dysrhythmias associated with DA treatment in comparison to NE treatment of septic shock.

CLINICAL IMPLICATIONS: While there was no significant difference in mortality between the two vasopressor regimens, the significant increase in dysrhythmias associated with DA administration raises significant safety concerns. Further testing is needed to confirm the safety of dopamine and ensure that it is not detrimental to septic shock patients.

DISCLOSURE: Jaime Simon Grahe, None.

Jaime J. Simon Grahe DO * Gourang P. Patel PharmD Ellen Elpern RN Robert A. Balk MD Rush University Medical Center, Chicago, IL

COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group

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