Norepinephrine in Pregnancy and Breastfeeding
Risk Factor: C
Class: Autonomics
/ Sympathomimetics (adrenergics)
Fetal Risk Summary
Norepinephrine (noradrenaline; levarterenol) is a direct-acting adrenergic agent that is used for acute hypotension and as an adjunct in the treatment of cardiac arrest. It is a mixture of the racemic stereoisomer and is given by IV infusion. Norepinephrine readily crosses the placenta (1), consistent with its relatively low molecular weight (about 169).
In animal reproduction studies, norepinephrine has caused situs inversus (rat embryos) (l-isomer only; no effect from d-form) (2), cataract (rat embryos) (3), hemorrhages of cephalic, skin, and extremity structures (chick embryo) (4), and microscopic liver abnormalities and delayed skeletal ossification (hamsters) (5).
In a 1995 study in pregnant ewes (123137 days' gestation), a high maternal dose (40 g/minute) of norepinephrine given by IV infusion caused a significant decrease in maternal placental blood flow (6). Although fetal arterial pressure did not change, transient (2.5 hours) but statistically significant decreases in fetal oxygenation, fetal urine flow, and lung liquid flow were observed. Because the average human maintenance dose is much less (about 24 g/minute), the clinical significance of these changes to a human fetus is unknown.
Uterine vessels are normally maximally dilated, and they have only a-adrenergic receptors (7). Use of the a- and b-adrenergic stimulant norepinephrine could cause constriction of these vessels and reduce uterine blood flow, thereby producing fetal hypoxia (bradycardia). Norepinephrine may also interact with oxytocics or ergot derivatives to produce severe persistent maternal hypertension (7). Rupture of a cerebral vessel is possible. If a pressor agent is indicated, other drugs, such as ephedrine, should be considered.
Breast Feeding Summary
No reports describing the use of norepinephrine in lactation have been located. Use of the agent during breast feeding would not be expected because of the indications for use.
References
- Morgan CD, Sandler M, Panigel M. Placental transfer of catecholamines in vitro and in vivo. Am J Obstet Gynecol 1972;112:106875.
- Fujinaga M, Maze M, Hoffman BB, Baden JM. Activation of a-1 adrenergic receptors modulates the control of left/right sidedness in rat embryos. Development Biology 1992;150:41921. As cited in Shepard TH. Catalog of Teratogenic Agents. 9th ed. Baltimore, MD: The Johns Hopkins University Press, 1998:340.
- Pitel M, Lerman S. Studies on the fetal rat lens. Effects of intrauterine adrenalin and noradrenalin. Invest Ophthalmol 1962;1:40612. As cited in Shepard TH. Catalog of Teratogenic Agents. 9th ed. Baltimore, MD: The Johns Hopkins University Press, 1998:340.
- Gatling RR. The effect of sympathomimetic agents on the chick embryo. Am J Pathol 1962;40:11327.
- Hirsch KS, Fritz HI. A comparison of mescaline with epinephrine and norepinephrine in the hamster. Teratology 1974;9:A19A20. As cited in Schardein TH. Chemically Induced Birth Defects. 3rd ed. New York, NY: Marcel Dekker, 2000:360, 364.
- Stevens AD, Lumbers ER. Effects of intravenous infusions of noradrenaline into the pregnant ewe on uterine blood flow, fetal renal function, and lung liquid flow. Can J Physiol Pharmacol 1995;73:2028.
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Smith NT, Corbascio AN. The use and misuse of pressor agents. Anesthesiology 1970;33:58101.
Questions and Answers
Norepinephrine?, What other types of interations (two, if possible), other than Van der Waals or hydrophobic forces, could cause a neurotransmitter (norepinephrine) to bind to the nerve receptors?
Hydrogen bonding
Covalent bond
Covalent isn't likely because of the rapid on-off rates for norepi at both the alpha and beta receptors, but you asked for 2, so I threw that one in.
What happens to Noradrenaline/Norepinephrine in the synaptic cleft?, Am I right in thinking that Noradrenaline/Norepinephrine released in the synaptic cleft gets removed by been broken down to small inactive componets which then get abosorbed back into the pre-synaptic cleft to be resynthesised to Noradrenaline/Norepinephrine? If I am right, any further detail would be great. Thanks alot.
Details are not known. But norepinephrine and noradrenaline are deaminated,methylated and products released to tissue fluids whence they are detoxicated. These hormones are not recycled.
What is Norepinephrine - is it natural is it involved in increasing the heart rate?, I was readin the web site for Hydroxycut Hardcore and saw this word - i cant even say it let alone understand what Wikipedia was trying to say when i look it up - apparently Hydroxycut Hardcore raises Norepinephrine by 40% what does this mean?
It is a fat burning hormone and neurotransmitter in the brain. It means that it increases the fat burning hormone to help you lose weight faster. Yes it does increase the heart rate as it does the following:
"Norepinephrine is similar to adrenaline. It works by constricting (narrowing) the blood vessels and increasing blood pressure and blood glucose (sugar) levels."
Michelle
What affect does prozac have on neurotransmitters such as norepinephrine and dopamine?, I suffer with depression, but also anxiety and paranoia. I take prozac which helps the depression but seem to make the anxiety and paranoia worse. I understand these issues are caused by high levels of norepinephrine and dopamine in the brain.
Prozac have very little effect on norepinephrine and dopamine in the brain, taking a low dose of a typical antipsychotic will help with the anxiety and paranoia.
What happenes when the brain has too much norepinephrine?, My doctor prescribed me cymbalta and i read that it increase serotonin and norepinephrine. I need the drug for my anxiety, and not really depression. If im not mistaken, norepinephrine increases your heart rate and is what causes you to 'fight or flight'. Im just curious to why he would prescribe something that increases an anxiety related neurotransmitter? Im always skeptical before taking medications, but Im willing to try...
Norepinephrine and dopamine are responsible for alertness and excitement. Low levels of norepinephrine and dopamine may make one feel anxious.
A change in diet would probably work better than drugs. Since you're a recovering alcoholic, you have a different brain chemistry than other people. It's hereditary. There are proven ways to heal your neurotransmitters and increase your serotonin, (etc.) with food.
What's the difference between Epinephrine and Norepinephrine?, My textbook vaguely says that epinephrine (adrenaline) and norepinephrine (noradrenalin) are hormones by the adrenal medulla that has similar effects (i.e. increase heart rate....)
But I'm wondering if anyone know the difference between the two. They can't be exactly the same...
Appreciate your response.
Well actually their functions are the same except ephinephrine is stronger or is more prominent compared to norephinephrine.
But for sure and for more info...check the links :)
How many milliliters are in one mole of norepinephrine?, Norepinephrine has a MM of approx. 167 grams per mole.
22400 milliliters
Why?
Because 1 mol of any particles contains 22.4 liters, and since you're asking for 1 mol of norepinephrine, then simply multiply 22.4•1000 to get your milliliters value.
If a patient dies from Norepinephrine or Epinephrine overdose, can you identify which compound is the culprit?, my professor asked how you would look at the urine to tell if the patient died from a epinephrine or norepinephrine overdose. This is for my pharm chem class. thx if u know the answer.
Well, epinephrine is synthesized from norepinephrine.
If the overdose were from norepinephrine (norepi), then one would expect high levels of normetanephrine and VMA and epinephrine in the urine. If it were epinephrine overdose you would see more metanephrine and VMA and less epinephrine in the urine.
Both catacholamines are metabolized in similar pathways.
Since dopamine is also a precursor to these two neurotransmitters hormones, then a urine result which had high homovanillic acid (HVA) levels would be indicative of dopamine overdose.
An drug that blocks the effect or norepinephrine on alpha-1 receptor sites would be expected to have what effe, An drug that blocks the effect or norepinephrine on alpha-1 receptor sites would be expected to have what effect on blood pressure?
obviously would result in a decreased b/p!
what are the differences between epinephrine and norepinephrine?, are they the same? if not can you tell me the difference and give me an example if you can...thanks!
hello,
both Norepinephrine & Epinephrine have sympathatic action.
and boths are hormons released from the adrenal medulla and neurotrasmitters in the nervous system.
here are THE DIFFERENCES:
1.BOISYNTHESIS : their biosynthetic pathway :
The amino acid L-tyrosin --->L-Dopa --->Dopamine---> Norepinephrine---> Epinephrine.
so, even in thier chemical structure there is slight difference.
2.THE ADRENERGIC RECEPTORS :
both of them are agonists for Alpha (1,2) , and Beta receptors (But Epinephrine has higher affinity for Beta-2 adrenergic receptor than Norepinephrine),and this is very important in the clinical use, and i will give you examples after i will tell you the effect of both Alpha and Beta receptors(specifically Beta-2)
ALPHA : Vasoconstriction (both arteries and viens , eg. in skin and GI system) to shift the perfusion of blood to the organs needed during Fight-or-Flight (eg.Heart,skeletal muscles).
BETA-2 : 1.Smooth muscle relaxation (eg. Bronchi)
2.Vasodilatation (eg.Coronary arteries,Arteries for skeletal muscles) so, to increase the perfusion of organ needed during Fight-or-Flight.
So,Norepinephrine (Vasoconstriction) ,Epinephrine (Vasoconstriction & Vasodilatation)
3.EXAMPLES :
ASTHMATIC ATTACK--->epinephrine is the one.
HYPOTENSION--->norepinephrine or dopamin.
Good luck.
