Shopping on line can be easy, simple and save you lots of money. It can also take a lot of your time, frustrate you, and result in unwanted purchases. Now the same can be said for regular high street shopping, but with the vast opportunity presented by the Internet it will pay you to spend a few minutes reading this and understanding how to better optimize your Adrenaline shopping experience:
1. Compare - without doubt the biggest advantage that the Adrenaline offers shoppers today is the ability to compare thousands of Adrenaline at a time. This is a great thing, but not necessarily all the time! Too much can be daunting at times so take advantage of the great comparison sites and where possible let them do the hard work for you.
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3. Testimonials - don't know anybody that has bought a Adrenaline? Wrong! If the Adrenaline is good the internet will let you know. Use the Internet as a friend and get testimonials before you buy.
4. Questions - Got a question about Adrenaline then search the Forums, FAQ's, Blogs etc. Don't be afraid to ask .....
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6. Returns - still worried that even after all of the above your Adrenaline wont be what you want? Check out the returns policy. There is so much competition now that someone, somewhere is bound to offer the terms that you are comfortable with.
7. Feedback - happy with your Adrenaline then let people know, after all you are depending on others people input in your buying decision, so why not give a little back.
8. Security - check for the yellow padlock on the Adrenaline site before you buy, and the s after http:/ /i.e. https:// = a secure site
9. Contact - got a question about Adrenaline, or want to leave a comment then check out the sites contact page. Reputable companies have them and respond.
10. Payment - ready to pay for your Adrenaline, then use your credit card or PayPal! Be aware of companies that don't accept them, there may be genuine reasons but given the huge amount of choice you have when buying online there is no reason at all not to buy via credit card or PayPal.
{{drugbox || width = 200| image = Adrenaline_chemical_structure.png| image2 = Epinephrine-3d-CPK.png|imagename=
(R)-(−)-L-Epinephrine or
(R)-(−)-L-adrenaline|IUPAC_name =
(R)-4-(1-hydroxy-
2-(methylamino)ethyl)benzene-1,2-diol|CAS_number = 51-43-4|ATC_prefix = A01|ATC_suffix = AD01|ATC_supplemental = |PubChem = 838|DrugBank = APRD00450|C = 9 | H = 13 | N = 1 | O = 3|molecular_weight = 183.204 g/mol|bioavailability = Nil (oral)|metabolism =
synapse (Monoamine oxidase and
Catechol-O-methyl transferase)|elimination_half-life = 2 minutes|excretion = n/a|pregnancy_AU = A|pregnancy_US = C|legal_AU = S4|legal_US = Rx-only|legal_UK = POM|routes_of_administration =
intravenous,
intramuscular, endotracheal tube-->
Epinephrine (
International Nonproprietary Name) (
International Phonetic Alphabet: ) or
adrenaline (European Pharmacopoeia and British Approved Name) (
International Phonetic Alphabet: ), sometimes spelled "epinephrin" or "adrenalin" respectively, is a hormone when carried in the blood and a
neurotransmitter when it is released across a neuronal synapse. It is a
catecholamine, a sympathomimetic monoamine derived from the amino acids phenylalanine and
tyrosine. The Latin roots
ad-+
renes and the Greek language roots
epi-+
nephros both literally mean "on/to the
kidney" (referring to the adrenal gland, which sits atop the kidneys and secretes epinephrine). Epinephrine is sometimes shortened to
epi or to
EP in medical jargon.
History
In May 1886, William Horatio Bates reported the discovery of a substance produced by the
adrenal gland in the
New York Medical Journal. Epinephrine was isolated and identified in 1895 by
Napoleon Cybulski, a
Poland physiology. The discovery was repeated in 1897 by John Jacob Abel.Aronson JK (2000). " Where name and image meet" - the argument for "adrenaline".
British Medical Journal 320, 506-9.
Jokichi Takamine, a Japanese chemist, independently discovered the same hormone in 1900.
It was first artificially synthesized in 1904 by Friedrich Stolz.
Actions in the body
Epinephrine is a "Fight-or-flight response" hormone which is released from the adrenal glands when danger threatens or in an emergency. When secreted into the bloodstream, it rapidly prepares the body for action in emergency situations. The hormone boosts the supply of oxygen and glucose to the brain and muscles, while suppressing other non-emergency bodily processes (digestion in particular).
Epinephrine plays a central role in the short-term
Stress (medicine) reaction—the physiological response to threatening, exciting, or environmental
stressor conditions such as high noise health effects levels or
over-illumination (
see Fight-or-flight response). It is secreted by the
adrenal medulla. When released into the bloodstream, epinephrine binds to multiple adrenergic receptors and has numerous effects throughout the body. It increases heart rate and
stroke volume, dilates the pupils, and constricts
arterioles in the skin and gut while dilating arterioles in leg muscles. It elevates the blood sugar level by increasing
catalysis of glycogen to
glucose in the liver, and at the same time begins the breakdown of
lipids in adipocyte. Like some other stress hormones, epinephrine has a suppressive effect on the
immune system. Epinephrine - Online Medical Dictionary
Although epinephrine does not have any psychoactive effects, stress or arousal also releases norepinephrine in the brain. Norepinephrine has similar actions in the body, but is also psychoactive.
Epinephrine is used as a
medication to treat
cardiac arrest and other
cardiac dysrhythmias resulting in diminished or absent
cardiac output; its action is to increase peripheral resistance via alpha adrenergic receptor vasoconstriction, so that blood is shunted to the body's core, and the
beta adrenergic receptor response which is increased cardiac rate and output (the speed and pronouncement of heart beats). This beneficial action comes with a significant negative consequence—increased cardiac irritability—which may lead to additional complications immediately following an otherwise successful resuscitation. Alternatives to this treatment include
vasopressin, a powerful antidiuretic which also increases peripheral vascular resistance leading to blood shunting via vasoconstriction, but without the attendant increase in myocardial irritability.
Because of its suppressive effect on the immune system, epinephrine is used to treat anaphylaxis and sepsis. Allergy patients undergoing immunotherapy may receive an epinephrine rinse before the allergen extract is administered, thus reducing the immune response to the administered allergen. It is also used as a bronchodilator for asthma if specific
beta2-adrenergic receptor agonists are unavailable or ineffective. Adverse reactions to epinephrine include palpitations,
tachycardia, anxiety, headache, tremor,
hypertension, and acute
pulmonary edema. About.com - "The Definition of Epinephrine"
Biosynthesis
in a synthetic pathway shared by all catecholamines.
Epinephrine is synthesized from norepinephrine in a synthetic pathway shared by all catecholamines, including L-dopa,
dopamine, norepinephrine, and epinephrine.
Epinephrine is synthesized via methylation of the primary distal amine of
norepinephrine by phenylethanolamine N-methyltransferase (PNMT) in the cytosol of
adrenergic neurons and cells of the adrenal medulla (so-called
chromaffin cells). PNMT is only found in the cytosol of cells of adrenal medullary cells. PNMT uses S-Adenosylmethionine (SAMe) as a cofactor to donate the
methyl group to norepinephrine, creating epinephrine.
For norepinephrine to be acted upon by PNMT in the cytosol, it must first be shipped out of chromaffin granule of the chromaffin cells. This may occur via the catecholamine-H+ exchanger VMAT1. VMAT1 is also responsible for transporting newly synthesized epinephrine from the cytosol back into chromaffin granules in preparation for release.
Regulation
Epinephrine synthesis is solely under the control of the central nervous system (CNS). Several levels of regulation dominate epinephrine synthesis.
Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of epinephrine precursors by enhancing the activity of enzymes involved in
catecholamine synthesis. The specific enzymes are
tyrosine hydroxylase in the synthesis of Levodopa and enzyme dopamine-β-hydroxylase in the synthesis of
norepinephrine.
ACTH also stimulates the
adrenal cortex to release cortisol, which increases the expression of PNMT in chromaffin cells, enhancing epinephrine synthesis.
The sympathetic nervous system, acting via
splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine.
Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing cell depolarization and an influx of
calcium through
voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream.
Unlike many other hormones, epinephrine (as with other catecholamines) does not exert any negative feedback to
down-regulate its own synthesis.
A
pheochromocytoma is a tumor of the adrenal gland (or, rarely, the ganglia of the sympathetic nervous system), which results in the uncontrolled secretion of catecholamines, usually epinephrine.
In liver cells, epinephrine binds to the β-Adrenergic receptor which changes conformation and helps Gs, a G protein, exchange GDP to GTP. This trimeric G protein dissociates to Gs alpha and Gs beta/gamma subunits. Ga alpha binds to adenyl cyclase thus converting ATP into Cyclic AMP. Cyclic AMP binds to the regulatory subunit of Protein Kinase A: Protein kinase A phosphorylates Phosphorylase Kinase. Meanwhile, Gs beta/gamma binds to the calcium channel and allows calcium ions to enter the cytoplasm. Calcium ions bind to calmodulin proteins, a protein present in all eukaryotic cells, which then binds to Phosphorylase Kinase and finishes its activation. Phosphorylase Kinase phosphorylates Phosphorylase which then phosphorylates glycogen and converts it to glucose-6-phosphate.
Pharmacology
Epinephrine's actions are mediated through adrenergic receptors:
- Epinephrine also activates β-adrenergic receptors of the liver and muscle cells, thereby activating the adenylate cyclase signaling pathway, which will in turn increase glycogenolysis.
β2 receptors are found primarily in
skeletal muscle blood vessels where they trigger vasodilation. However, α-adrenergic receptors are found in most
smooth muscles and
splanchnic vessels, and epinephrine triggers vasoconstriction in those vessels.
Thus, depending on the patient, administration of epinephrine may
raise or
lower blood pressure, depending whether or not the net increase or decrease in peripheral resistance can balance the positive
inotropic and
chronotropic effects of epinephrine on the heart, effects which respectively increase the
contractility and heart rate of the heart.
Terminology
Although widely referred to as
adrenaline outside of the US, and the
laity worldwide, the United States Approved Name and International Nonproprietary Name for this chemical is
epinephrine because
adrenaline bore too much similarity to the Parke, Davis & Co trademark
adrenalin (without the "e") which was registered in the US. The British Approved Name and European Pharmacopoeia term for this chemical is
adrenaline, and is indeed now one of the few differences between the INN and BAN systems of names.
Amongst US health professionals, the term
epinephrine is used over
adrenaline. However, it should be noted that universally, pharmaceuticals that mimic the effects of epinephrine are called
adrenergics, and receptors for epinephrine are called
adrenoceptors.
Isomers
Natural epinephrine is the
(R)-(−)-L-epinephrine stereoisomer.
Autoinjectors
Epinephrine is now also used in
EpiPens and
Twinjects.
EpiPens are long narrow auto-injectors that administer epinephrine,
Twinjects are similar but contain two doses of epinephrine.
Though both
EpiPen and
Twinject are trademark names, common usage of the terms are drifting toward the
Genericized trademark of any epinephrine autoinjector.
See also
References
Notes
General references
{{drugbox || width = 200| image = Adrenaline_chemical_structure.png| image2 = Epinephrine-3d-CPK.png|imagename=
(R)-(−)-L-Epinephrine or
(R)-(−)-L-adrenaline|IUPAC_name =
(R)-4-(1-hydroxy-
2-(methylamino)ethyl)benzene-1,2-diol|CAS_number = 51-43-4|ATC_prefix = A01|ATC_suffix = AD01|ATC_supplemental = |PubChem = 838|DrugBank = APRD00450|C = 9 | H = 13 | N = 1 | O = 3|molecular_weight = 183.204 g/mol|bioavailability = Nil (oral)|metabolism =
synapse (
Monoamine oxidase and
Catechol-O-methyl transferase)|elimination_half-life = 2 minutes|excretion = n/a|pregnancy_AU = A|pregnancy_US = C|legal_AU = S4|legal_US = Rx-only|legal_UK = POM|routes_of_administration =
intravenous, intramuscular,
endotracheal tube-->
Epinephrine (International Nonproprietary Name) (
International Phonetic Alphabet: ) or
adrenaline (European Pharmacopoeia and British Approved Name) (International Phonetic Alphabet: ), sometimes spelled "epinephrin" or "adrenalin" respectively, is a
hormone when carried in the blood and a neurotransmitter when it is released across a neuronal synapse. It is a catecholamine, a sympathomimetic monoamine derived from the
amino acids
phenylalanine and
tyrosine. The
Latin roots
ad-+
renes and the
Greek language roots
epi-+
nephros both literally mean "on/to the
kidney" (referring to the
adrenal gland, which sits atop the kidneys and secretes epinephrine). Epinephrine is sometimes shortened to
epi or to
EP in medical jargon.
History
In May 1886,
William Horatio Bates reported the discovery of a substance produced by the
adrenal gland in the
New York Medical Journal. Epinephrine was isolated and identified in 1895 by Napoleon Cybulski, a
Poland physiology. The discovery was repeated in 1897 by John Jacob Abel.Aronson JK (2000). " Where name and image meet" - the argument for "adrenaline".
British Medical Journal 320, 506-9.
Jokichi Takamine, a Japanese chemist, independently discovered the same hormone in 1900.
It was first artificially synthesized in 1904 by
Friedrich Stolz.
Actions in the body
Epinephrine is a "Fight-or-flight response" hormone which is released from the adrenal glands when danger threatens or in an emergency. When secreted into the bloodstream, it rapidly prepares the body for action in emergency situations. The hormone boosts the supply of oxygen and glucose to the brain and muscles, while suppressing other non-emergency bodily processes (digestion in particular).
Epinephrine plays a central role in the short-term Stress (medicine) reaction—the physiological response to threatening, exciting, or environmental
stressor conditions such as high
noise health effects levels or
over-illumination (
see Fight-or-flight response). It is secreted by the adrenal medulla. When released into the bloodstream, epinephrine binds to multiple adrenergic receptors and has numerous effects throughout the body. It increases
heart rate and
stroke volume, dilates the
pupils, and constricts arterioles in the skin and gut while dilating arterioles in leg muscles. It elevates the blood sugar level by increasing
catalysis of glycogen to
glucose in the liver, and at the same time begins the breakdown of
lipids in
adipocyte. Like some other stress hormones, epinephrine has a suppressive effect on the
immune system. Epinephrine - Online Medical Dictionary
Although epinephrine does not have any psychoactive effects, stress or arousal also releases
norepinephrine in the brain. Norepinephrine has similar actions in the body, but is also psychoactive.
Epinephrine is used as a
medication to treat cardiac arrest and other cardiac dysrhythmias resulting in diminished or absent
cardiac output; its action is to increase peripheral resistance via alpha adrenergic receptor vasoconstriction, so that blood is shunted to the body's core, and the beta adrenergic receptor response which is increased cardiac rate and output (the speed and pronouncement of heart beats). This beneficial action comes with a significant negative consequence—increased cardiac irritability—which may lead to additional complications immediately following an otherwise successful resuscitation. Alternatives to this treatment include vasopressin, a powerful
antidiuretic which also increases peripheral vascular resistance leading to blood shunting via vasoconstriction, but without the attendant increase in myocardial irritability.
Because of its suppressive effect on the immune system, epinephrine is used to treat
anaphylaxis and sepsis. Allergy patients undergoing
immunotherapy may receive an epinephrine rinse before the allergen extract is administered, thus reducing the immune response to the administered allergen. It is also used as a
bronchodilator for asthma if specific
beta2-adrenergic receptor agonists are unavailable or ineffective. Adverse reactions to epinephrine include
palpitations,
tachycardia, anxiety, headache, tremor, hypertension, and acute
pulmonary edema. About.com - "The Definition of Epinephrine"
Biosynthesis
in a synthetic pathway shared by all catecholamines.
Epinephrine is synthesized from norepinephrine in a synthetic pathway shared by all catecholamines, including L-dopa, dopamine, norepinephrine, and epinephrine.
Epinephrine is synthesized via methylation of the primary distal amine of
norepinephrine by phenylethanolamine N-methyltransferase (PNMT) in the cytosol of
adrenergic neurons and cells of the
adrenal medulla (so-called chromaffin cells). PNMT is only found in the cytosol of cells of adrenal medullary cells. PNMT uses S-Adenosylmethionine (SAMe) as a cofactor to donate the methyl group to norepinephrine, creating epinephrine.
For norepinephrine to be acted upon by PNMT in the cytosol, it must first be shipped out of
chromaffin granule of the chromaffin cells. This may occur via the catecholamine-H+ exchanger
VMAT1. VMAT1 is also responsible for transporting newly synthesized epinephrine from the cytosol back into chromaffin granules in preparation for release.
Regulation
Epinephrine synthesis is solely under the control of the
central nervous system (CNS). Several levels of regulation dominate epinephrine synthesis.
Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of epinephrine precursors by enhancing the activity of enzymes involved in catecholamine synthesis. The specific enzymes are
tyrosine hydroxylase in the synthesis of
Levodopa and enzyme
dopamine-β-hydroxylase in the synthesis of norepinephrine.
ACTH also stimulates the
adrenal cortex to release cortisol, which increases the expression of PNMT in chromaffin cells, enhancing epinephrine synthesis.
The sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine.
Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on
nicotinic acetylcholine receptors, causing cell depolarization and an influx of
calcium through
voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream.
Unlike many other hormones, epinephrine (as with other catecholamines) does not exert any negative feedback to
down-regulate its own synthesis.
A pheochromocytoma is a tumor of the adrenal gland (or, rarely, the ganglia of the sympathetic nervous system), which results in the uncontrolled secretion of catecholamines, usually epinephrine.
In liver cells, epinephrine binds to the β-Adrenergic receptor which changes conformation and helps Gs, a G protein, exchange GDP to GTP. This trimeric G protein dissociates to Gs alpha and Gs beta/gamma subunits. Ga alpha binds to adenyl cyclase thus converting ATP into Cyclic AMP. Cyclic AMP binds to the regulatory subunit of Protein Kinase A: Protein kinase A phosphorylates Phosphorylase Kinase. Meanwhile, Gs beta/gamma binds to the calcium channel and allows calcium ions to enter the cytoplasm. Calcium ions bind to calmodulin proteins, a protein present in all eukaryotic cells, which then binds to Phosphorylase Kinase and finishes its activation. Phosphorylase Kinase phosphorylates Phosphorylase which then phosphorylates glycogen and converts it to glucose-6-phosphate.
Pharmacology
Epinephrine's actions are mediated through
adrenergic receptors:
- It binds to α1 receptors of liver cells, which activate inositol-phospholipid signaling pathway, signaling the phosphorylation of insulin, leading to reduced ability of insulin to bind to its receptors.
- Epinephrine also activates β-adrenergic receptors of the liver and muscle cells, thereby activating the adenylate cyclase signaling pathway, which will in turn increase glycogenolysis.
β2 receptors are found primarily in
skeletal muscle blood vessels where they trigger
vasodilation. However, α-adrenergic receptors are found in most
smooth muscles and splanchnic vessels, and epinephrine triggers
vasoconstriction in those vessels.
Thus, depending on the patient, administration of epinephrine may
raise or
lower blood pressure, depending whether or not the net increase or decrease in peripheral resistance can balance the positive
inotropic and chronotropic effects of epinephrine on the heart, effects which respectively increase the contractility and
heart rate of the heart.
Terminology
Although widely referred to as
adrenaline outside of the US, and the laity worldwide, the United States Approved Name and International Nonproprietary Name for this chemical is
epinephrine because
adrenaline bore too much similarity to the Parke, Davis & Co trademark
adrenalin (without the "e") which was registered in the US. The
British Approved Name and European Pharmacopoeia term for this chemical is
adrenaline, and is indeed now one of the few differences between the INN and BAN systems of names.
Amongst US health professionals, the term
epinephrine is used over
adrenaline. However, it should be noted that universally, pharmaceuticals that mimic the effects of epinephrine are called
adrenergics, and receptors for epinephrine are called
adrenoceptors.
Isomers
Natural epinephrine is the
(R)-(−)-L-epinephrine
stereoisomer.
Autoinjectors
Epinephrine is now also used in
EpiPens and
Twinjects.
EpiPens are long narrow auto-injectors that administer epinephrine,
Twinjects are similar but contain two doses of epinephrine.
Though both
EpiPen and
Twinject are trademark names, common usage of the terms are drifting toward the Genericized trademark of any epinephrine
autoinjector.
See also
References
Notes
General references
Adrenaline Alley
www.flickr.com/photos/guyglover and see some great pics of the faces and action at The Alley. Check out the new pics on Our Gallery - Training clubs
Definition: adrenaline from Online Medical Dictionary
The Online Medical Dictionary is a searchable dictionary of definitions from medicine, science and technology.
Adrenaline
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Zorbing is the original adrenaline craze from New Zealand - the ultimate thrill!
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Operate a RYA sailing school offering motor and sailing yachts for charter from Gosport. Vessel listings, course details, services offered and an online chandlery.
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Italian Rock and Metal label. Artists include Evil Wings, Moon of Steel, and Seasons of the Wolf. MP3s, tour schedule, online store, news, and links.
Adrenaline Alley
We would like to thank all our sponsors for all their support and dedication, we couldn't not progress Adrenaline Alley without them.
VIP Adrenaline Events Management, Gift Experiences, Corporate Events ...
Event management firm based in Lincolnshire. They supply team building days, corporate activity events and staff reward days.
Welcome to Adrenaline Creative, Cambridge-based design and marketing ...
Welcome to Adrenaline Creative, a Cambridge-based design and marketing<br /> agency with an infectious passion for branding, web design and graphic design
Adrenaline
Adrenaline - the front line treatment The treatment for a serious allergic reaction is adrenaline (also known as epinephrine).
