Adrenaline

Adrenaline

This article is about the natural hormone. For the medication, see Epinephrine (medication). For other uses, see Adrenaline (disambiguation).

Adrenaline, also known as epinephrine, is a hormone and medication[7][8] which is involved in regulating visceral functions (e.g., respiration).[7][9] Adrenaline is normally produced both by the adrenal glands and by a small number of neurons in the medulla oblongata. It plays an important role in the fight-or-flight response by increasing blood flow to muscles, output of the heart by acting on the SA node,[10] pupil dilation response and blood sugar level.[11][12] It does this by binding to alpha and beta receptors.[12] It is found in many animals and some single-celled organisms.[13][14] Polish physiologist Napoleon Cybulski first isolated adrenaline in 1895.[15]

Medical uses

Main article: Epinephrine (medication)

As a medication, it is used to treat a number of conditions including anaphylaxis, cardiac arrest, and superficial bleeding.[5] Inhaled adrenaline may be used to improve the symptoms of croup.[16] It may also be used for asthma when other treatments are not effective. It is given intravenously, by injection into a muscle, by inhalation, or by injection just under the skin.[5] Common side effects include shakiness, anxiety, and sweating. A fast heart rate and high blood pressure may occur. Occasionally it may result in an abnormal heart rhythm. While the safety of its use during pregnancy and breastfeeding is unclear, the benefits to the mother must be taken into account.[5]

A case has been made for the use of adrenaline infusion in place of the widely accepted treatment of inotropes for preterm infants with clinical cardiovascular compromise. Although there is sufficient data which strongly recommends adrenaline infusions as a viable treatment, more trials are needed in order to conclusively determine that these infusions will successfully reduce morbidity and mortality rates among preterm, cardiovascularly compromised infants.[17]

Physiological effects

The adrenal medulla is a minor contributor to total circulating catecholamines (L-DOPA is at a higher concentration in the plasma),[18] though it contributes over 90% of circulating adrenaline. Little adrenaline is found in other tissues, mostly in scattered chromaffin cells, and in a small number of neurons which use adrenaline as a neurotransmitter.[19] Following adrenalectomy, adrenaline disappears below the detection limit in the blood stream.[20]

Pharmacological doses of adrenaline stimulate α1, α2, β1, β2, and β3 adrenoceptors of the sympathetic nervous system. Sympathetic nerve receptors are classified as adrenergic, based on their responsiveness to adrenaline.[21] The term "adrenergic" is often misinterpreted in that the main sympathetic neurotransmitter is noradrenaline, rather than adrenaline, as discovered by Ulf von Euler in 1946.[22][23] Adrenaline does have a β2 adrenoceptor-mediated effect on metabolism and the airway, there being no direct neural connection from the sympathetic ganglia to the airway.[24][25][26]

The concept of the adrenal medulla and the sympathetic nervous system being involved in the flight, fight and fright response was originally proposed by Walter Bradford Cannon.[27] But the adrenal medulla, in contrast to the adrenal cortex, is not required for survival. In adrenalectomized patients hemodynamic and metabolic responses to stimuli such as hypoglycemia and exercise remain normal.[28][29]

Exercise

One physiological stimulus to adrenaline secretion is exercise. This was first demonstrated by measuring the dilation of a (denervated) pupil of a cat on a treadmill,[30] later confirmed using a biological assay on urine samples.[31] Biochemical methods for measuring catecholamines in plasma were published from 1950 onwards.[32] Although much valuable work has been published using fluorimetric assays to measure total catecholamine concentrations, the method is too non-specific and insensitive to accurately determine the very small quantities of adrenaline in plasma. The development of extraction methods and enzyme-isotope derivate radio-enzymatic assays (REA) transformed the analysis down to a sensitivity of 1 pg for adrenaline.[33] Early REA plasma assays indicated that adrenaline and total catecholamines rise late in exercise, mostly when anaerobic metabolism commences.[34][35][36]

During exercise, the adrenaline blood concentration rises partially from the increased secretion of the adrenal medulla and partly from the decreased metabolism of adrenaline due to reduced blood flow to the liver.[37] Infusion of adrenaline to reproduce exercise circulating concentrations of adrenaline in subjects at rest has little haemodynamic effect, other than a small β2-mediated fall in diastolic blood pressure.[38][39] Infusion of adrenaline well within the physiological range suppresses human airway hyper-reactivity sufficiently to antagonize the constrictor effects of inhaled histamine.[40]

A link between the sympathetic nervous system and the lungs was shown in 1887 when Grossman showed that stimulation of cardiac accelerator nerves reversed muscarine-induced airway constriction.[41] In experiments in the dog, where the sympathetic chain was cut at the level of the diaphragm, Jackson showed that there was no direct sympathetic innervation to the lung, but that bronchoconstriction was reversed by release of adrenaline from the adrenal medulla.[42] An increased incidence of asthma has not been reported for adrenalectomized patients; those with a predisposition to asthma will have some protection from airway hyper-reactivity from their corticosteroid replacement therapy. Exercise induces progressive airway dilation in normal subjects that correlates with work load and is not prevented by beta blockade.[43] The progressive dilation of the airway with increasing exercise is mediated by a progressive reduction in resting vagal tone. Beta blockade with propranolol causes a rebound in airway resistance after exercise in normal subjects over the same time course as the bronchoconstriction seen with exercise induced asthma.[44] The reduction in airway resistance during exercise reduces the work of breathing.[45]

Emotional response

Every emotional response has a behavioral component, an autonomic component, and a hormonal component. The hormonal component includes the release of adrenaline, an adrenomedullary response that occurs in response to stress and that is controlled by the sympathetic nervous system. The major emotion studied in relation to adrenaline is fear. In an experiment, subjects who were injected with adrenaline expressed more negative and fewer positive facial expressions to fear films compared to a control group. These subjects also reported a more intense fear from the films and greater mean intensity of negative memories than control subjects.[46] The findings from this study demonstrate that there are learned associations between negative feelings and levels of adrenaline. Overall, the greater amount of adrenaline is positively correlated with an aroused state of negative feelings. These findings can be an effect in part that adrenaline elicits physiological sympathetic responses including an increased heart rate and knee shaking, which can be attributed to the feeling of fear regardless of the actual level of fear elicited from the video. Although studies have found a definite relation between adrenaline and fear, other emotions have not had such results. In the same study, subjects did not express a greater amusement to an amusement film nor greater anger to an anger film.[46] Similar findings were also supported in a study that involved rodent subjects that either were able or unable to produce adrenaline. Findings support the idea that adrenaline does have a role in facilitating the encoding of emotionally arousing events, contributing to higher levels of arousal due to fear.[47]

Memory

It has been found that adrenergic hormones, such as adrenaline, can produce retrograde enhancement of long-term memory in humans. The release of adrenaline due to emotionally stressful events, which is endogenous adrenaline, can modulate memory consolidation of the events, ensuring memory strength that is proportional to memory importance. Post-learning adrenaline activity also interacts with the degree of arousal associated with the initial coding.[48] There is evidence that suggests adrenaline does have a role in long-term stress adaptation and emotional memory encoding specifically. Adrenaline may also play a role in elevating arousal and fear memory under particular pathological conditions including post-traumatic stress disorder.[47] Overall, "Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects.”[49] Studies have also found that recognition memory involving adrenaline depends on a mechanism that depends on β adrenoceptors.[49] Adrenaline does not readily cross the blood–brain barrier, so its effects on memory consolidation are at least partly initiated by β adrenoceptors in the periphery. Studies have found that sotalol, a β adrenoceptor antagonist that also does not readily enter the brain, blocks the enhancing effects of peripherally administered adrenaline on memory.[50] These findings suggest that β adrenoceptors are necessary for adrenaline to have an effect on memory consolidation.

Pathology

Increased adrenaline secretion is observed in pheochromocytoma, hypoglycemia, myocardial infarction and to a lesser degree in essential tremor (also known as benign, familial or idiopathic tremor). A general increase in sympathetic neural activity is usually accompanied by increased adrenaline secretion, but there is selectivity during hypoxia and hypoglycaemia, when the ratio of adrenaline to noradrenaline is considerably increased.[51][52][53] Therefore, there must be some autonomy of the adrenal medulla from the rest of the sympathetic system.

Myocardial infarction is associated with high levels of circulating adrenaline and noradrenaline, particularly in cardiogenic shock.[54][55]

Benign familial tremor (BFT) is responsive to peripheral β adrenergic blockers and β2-stimulation is known to cause tremor. Patients with BFT were found to have increased plasma adrenaline, but not noradrenaline.[56][57]

Low, or absent, concentrations of adrenaline can be seen in autonomic neuropathy or following adrenalectomy. Failure of the adrenal cortex, as with Addison's disease, can suppress adrenaline secretion as the activity of the synthesing enzyme, phenylethanolamine-N-methyltransferase, depends on the high concentration of cortisol that drains from the cortex to the medulla.[58][59][60]

Terminology

In 1901, Jōkichi Takamine patented a purified extract from the adrenal glands which was trademarked by Parke, Davis & Co in the US.[61] The British Approved Name and European Pharmacopoeia term for this drug is hence adrenaline.[62]

However, the pharmacologist John Abel had already prepared an extract from adrenal glands as early as 1897, and coined the name epinephrine to describe it (from the Greek epi and nephros, "on top of the kidneys").[61] In the belief that Abel's extract was the same as Takamine's (a belief since disputed), epinephrine became[when?] the generic name in the US,[61] and remains the pharmaceutical's United States Adopted Name and International Nonproprietary Name (though the name adrenaline is frequently used[63]).

The terminology is now one of the few differences between the INN and BAN systems of names.[64] Although European health professionals and scientists preferentially use the term adrenaline, the converse is true among American health professionals and scientists. Nevertheless, even among the latter, receptors for this substance are called adrenergic receptors or adrenoceptors, and pharmaceuticals that mimic its effects are often called adrenergics. The history of adrenaline and epinephrine is reviewed by Rao.[65]

Mechanism of action

See also: Adrenergic receptor

7x speed timelapse video of fish melanophores responding to 200µM adrenaline

As a hormone, adrenaline acts on nearly all body tissues by binding to adrenergic receptors. Its effects on various tissues depend of the type of tissue and expression of specific forms of adrenergic receptors. For example, high levels of adrenaline causes smooth muscle relaxation in the airways but causes contraction of the smooth muscle that lines most arterioles.

Adrenaline is a nonselective agonist of all adrenergic receptors, including the major subtypes α1, α2, β1, β2, and β3.[66] Adrenaline's binding to these receptors triggers a number of metabolic changes. Binding to α-adrenergic receptors inhibits insulin secretion by the pancreas, stimulates glycogenolysis in the liver and muscle,[67] and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle.[68][69] β adrenergic receptor binding triggers glucagon secretion in the pancreas, increased adrenocorticotropic hormone (ACTH) secretion by the pituitary gland, and increased lipolysis by adipose tissue. Together, these effects lead to increased blood glucose and fatty acids, providing substrates for energy production within cells throughout the body.[69]

Adrenaline causes liver cells to release glucose into the blood, acting through both alpha and beta adrenergic receptors to stimulate glycogenolysis. Adrenaline binds to β2 receptors on liver cells, which changes conformation and helps Gs, a heterotrimeric G protein, exchange GDP to GTP. This trimeric G protein dissociates to Gs alpha and Gs beta/gamma subunits. Gs alpha stimulates adenylyl cyclase, thus converting adenosine triphosphate into cyclic adenosine monophosphate (AMP). Cyclic AMP activates protein kinase A. Protein kinase A phosphorylates and partially activates phosphorylase kinase. Adrenaline also binds to α1 adrenergic receptors, causing an increase in inositol trisphosphate, inducing calcium ions to enter the cytoplasm. Calcium ions bind to calmodulin, which leads to further activation of phosphorylase kinase. Phosphorylase kinase phosphorylates glycogen phosphorylase, which then breaks down glycogen leading to the production of glucose.[70]

Adrenaline also has significant effects on the cardiovascular system. It increases peripheral resistance via α1 receptor-dependent vasoconstriction and increases cardiac output by binding to β1 receptors. The goal of reducing peripheral circulation is to increase coronary and cerebral perfusion pressures and therefore increase oxygen exchange at the cellular level. While adrenaline does increase aortic, cerebral, and carotid circulation pressure, it lowers carotid blood flow and end-tidal CO2 or ETCO2 levels. It appears that adrenaline may be improving macrocirculation at the expense of the capillary beds where actual perfusion is taking place.[73]

Measurement in biological fluids

Adrenaline may be quantified in blood, plasma or serum as a diagnostic aid, to monitor therapeutic administration, or to identify the causative agent in a potential poisoning victim. Endogenous plasma adrenaline concentrations in resting adults are normally less than 10 ng/L, but may increase by 10-fold during exercise and by 50-fold or more during times of stress. Pheochromocytoma patients often have plasma adrenaline levels of 1000–10,000 ng/L. Parenteral administration of adrenaline to acute-care cardiac patients can produce plasma concentrations of 10,000 to 100,000 ng/L.[74][75]

Biosynthesis and regulation

The biosynthesis of adrenaline involves a series of enzymatic reactions.

In chemical terms, adrenaline is one of a group of monoamines called the catecholamines. Adrenaline is synthesized in the chromaffin cells of the adrenal medulla of the adrenal gland and a small number of neurons in the medulla oblongata in the brain through a metabolic pathway that converts the amino acids phenylalanine and tyrosine into a series of metabolic intermediates and, ultimately, adrenaline.[7][9][76] Tyrosine is first oxidized to L-DOPA by tyrosine hydroxylase, this is the rate-limiting step. Then it is subsequently decarboxylated to give dopamine by DOPA decarboxylase (aromatic L-amino acid decarboxylase). Dopamine is then converted to noradrenaline by dopamine beta-hydroxylase which utilizes ascorbic acid (vitamin C) and copper. The final step in adrenaline biosynthesis is the methylation of the primary amine of noradrenaline. This reaction is catalyzed by the enzyme phenylethanolamine N-methyltransferase (PNMT) which utilizes S-adenosyl methionine (SAMe) as the methyl donor.[77] While PNMT is found primarily in the cytosol of the endocrine cells of the adrenal medulla (also known as chromaffin cells), it has been detected at low levels in both the heart and brain.[78]

Regulation

The major physiologic triggers of adrenaline release center upon stresses, such as physical threat, excitement, noise, bright lights, and high or low ambient temperature. All of these stimuli are processed in the central nervous system.[82]

Adrenocorticotropic hormone (ACTH) and the sympathetic nervous system stimulate the synthesis of adrenaline precursors by enhancing the activity of tyrosine hydroxylase and dopamine β-hydroxylase, two key enzymes involved in catecholamine synthesis. ACTH also stimulates the adrenal cortex to release cortisol, which increases the expression of PNMT in chromaffin cells, enhancing adrenaline synthesis. This is most often done in response to stress. The sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of adrenaline. 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 adrenaline (and noradrenaline) into the bloodstream. For noradrenaline to be acted upon by PNMT in the cytosol, it must first be shipped out of granules of the chromaffin cells. This may occur via the catecholamine-H+ exchanger VMAT1. VMAT1 is also responsible for transporting newly synthesized adrenaline from the cytosol back into chromaffin granules in preparation for release.[83]

Unlike many other hormones adrenaline (as with other catecholamines) does not exert negative feedback to down-regulate its own synthesis.[84] Abnormally elevated levels of adrenaline can occur in a variety of conditions, such as surreptitious adrenaline administration, pheochromocytoma, and other tumors of the sympathetic ganglia.

Its action is terminated with reuptake into nerve terminal endings, some minute dilution, and metabolism by monoamine oxidase[85] and catechol-O-methyl transferase.

History

Main article: History of catecholamine research

Extracts of the adrenal gland were first obtained by Polish physiologist Napoleon Cybulski in 1895. These extracts, which he called nadnerczyna ("adrenalin"), contained adrenaline and other catecholamines.[86] American ophthalmologist William H. Bates discovered adrenaline's usage for eye surgeries prior to 20 April 1896.[87] In 1897, John Jacob Abel (1857-1938), the father of modern pharmacology, finds a natural substance produced by the adrenal glands that he names epinephrine. The first hormone to be identified, it remains a crucial, first line treatment for cardiac arrests, severe allergic reactions and other conditions. Japanese chemist Jōkichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900.[88][89] In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen.[90] Adrenaline was first synthesized in the laboratory by Friedrich Stolz and Henry Drysdale Dakin, independently, in 1904.[89]

Even though secretin is mentioned as the first hormone, adrenaline is the actual first hormone since the discovery of activity of adrenal extract on blood pressure was observed in 1895 before that of secretin in 1902.[91] In 1895, George Oliver (1841-1915), a general practitioner in North Yorkshire and Edward Albert Schäfer (1850-1935), a physiologist at University College of London published a paper about the active component of adrenal gland extract causing the increase in blood pressure and heart rate was from medulla, but not the cortex of the adrenal gland.[92] In 1897, John Jacob Abel (1857-1938) of Johns Hopkins University, the first chairman of the first U.S department of pharmacology, found a compound called epinephrine with the molecular formula of C17H15NO4.[91] Abel claimed his principle from adrenal gland extract was active. In 1900, Jōkichi Takamine (1854-1922), a Japanese chemist worked with his assistant, Keizo Uenaka [ja] (1876-1960) to purified a 2000 times more active principle than epinephrine from adrenal gland, named adrenaline with the molecular formula C10H15NO3.[91][92] In addition, in 1900 Thomas Aldrich of Parke-Davis Scientific Laboratory also purified adrenaline independently. Takamine and Parke-Davis later in 1901 both got the patent for adrenaline. The fight for terminology between adrenaline and epinephrine was not ended until the first adrenaline structural discovery of Hermann Pauly (1870-1950) in 1903, and the first adrenaline synthesis of Friedrich Stolz (1860-1936), a German chemist in 1904. They both believed that Takamine's compound was the active principle while Abel's compound was the inactive one.

Society and culture

Adrenaline junkie

See also: Novelty seeking

An adrenaline junkie is somebody who engages in sensation-seeking behavior through "the pursuit of novel and intense experiences without regard for physical, social, legal or financial risk".[93] Such activities include extreme and risky sports, substance abuse, unsafe sex, and crime. The term relates to the increase in circulating levels of adrenaline during physiological stress.[94] Such an increase in the circulating concentration of adrenaline is secondary to activation of the sympathetic nerves innervating the adrenal medulla, as it is rapid and not present in animals where the adrenal gland has been removed.[95] Although such stress triggers adrenaline release, it also activates many other responses within the central nervous system reward system which drives behavioral responses, so while the circulating adrenaline concentration is present, it may not drive behavior. Nevertheless, adrenaline infusion alone does increase alertness[96] and has roles in the brain including the augmentation of memory consolidation.[94]

Strength

Main article: Hysterical strength

Adrenaline has been implicated in feats of great strength, often occurring in times of crisis. For example, there are stories of a parent lifting part of a car when their child is trapped underneath.[97][98]

What is Adrenaline?

When a stressful situation occurs and your heart begins to race, your hands begin to sweat, and you start looking for an escape, you have experienced a textbook case of fight-or-flight response. This response stems from the hormone adrenaline. Also called epinephrine, this hormone is a crucial part of the body's fight-or-flight response, but over-exposure can be damaging to health. Because of this, adrenaline is a hormone worth understanding.

Adrenaline is produced in the medulla in the adrenal glands as well as some of the central nervous system's neurons. Within a couple of minutes during a stressful situation, adrenaline is quickly released into the blood, sending impulses to organs to create a specific response.

What is the function of adrenaline?

Adrenaline triggers the body's fight-or-flight response. This reaction causes air passages to dilate to provide the muscles with the oxygen they need to either fight danger or flee. Adrenaline also triggers the blood vessels to contract to re-direct blood toward major muscle groups, including the heart and lungs. The body's ability to feel pain also decreases as a result of adrenaline, which is why you can continue running from or fighting danger even when injured. Adrenaline causes a noticeable increase in strength and performance, as well as heightened awareness, in stressful times. After the stress has subsided, adrenaline’s effect can last for up to an hour.

Problems associated with adrenaline

Adrenaline is an important part of your body's ability to survive, but sometimes the body will release the hormone when it is under stress but not facing real danger. This can create feelings of dizziness, light-headedness, and vision changes. Also, adrenaline causes a release of glucose, which a fight-or-flight response would use. When no danger is present, that extra energy has no use, and this can leave the person feeling restless and irritable. Excessively high levels of the hormone due to stress without real danger can cause heart damage, insomnia, and a jittery, nervous feeling.

Medical conditions that cause an overproduction of adrenaline are rare, but can happen. If an individual has tumors on the adrenal glands, for example, he/she may produce too much adrenaline; leading to anxiety, weight loss, palpitations, rapid heartbeat, and high blood pressure. Too little adrenaline rarely occurs, but if it did it would limit the body's ability to respond properly in stressful situations.

Questions for your doctor

Adrenaline rarely causes problems, but ongoing stress can cause complications associated with adrenaline. Addressing these problems starts with finding healthy ways to deal with stress. Consider asking your doctor:

How can I tell if I am dealing with excessive adrenaline?

How can I reduce stress in my life?

Could adrenaline be causing my symptoms?

What affect is adrenaline function and stress having on my overall health?

Adrenaline Rush: Everything You Should Know

What is adrenaline?

Adrenaline, also called epinephrine, is a hormone released by your adrenal glands and some neurons.

The adrenal glands are located at the top of each kidney. They are responsible for producing many hormones, including aldosterone, cortisol, adrenaline, and noradrenaline. Adrenal glands are controlled by another gland called the pituitary gland.

The adrenal glands are divided into two parts: outer glands (adrenal cortex) and inner glands (adrenal medulla). The inner glands produce adrenaline.

Adrenaline is also known as the “fight-or-flight hormone.” It’s released in response to a stressful, exciting, dangerous, or threatening situation. Adrenaline helps your body react more quickly. It makes the heart beat faster, increases blood flow to the brain and muscles, and stimulates the body to make sugar to use for fuel.

When adrenaline is released suddenly, it’s often referred to as an adrenaline rush.

What happens in the body when you experience a rush of adrenaline?

An adrenaline rush begins in the brain. When you perceive a dangerous or stressful situation, that information is sent to a part of the brain called the amygdala. This area of the brain plays a role in emotional processing.

If danger is perceived by the amygdala, it sends a signal to another region of the brain called the hypothalamus. The hypothalamus is the command center of the brain. It communicates with the rest of the body through the sympathetic nervous system.

The hypothalamus transmits a signal through autonomic nerves to the adrenal medulla. When the adrenal glands receive the signal, they respond by releasing adrenaline into the bloodstream.

Once in the bloodstream, adrenaline:

binds to receptors on liver cells to break down larger sugar molecules, called glycogen, into a smaller, more readily usable sugar called glucose; this gives your muscles a boost of energy

binds to receptors on muscle cells in the lungs, causing you to breath faster

stimulates cells of the heart to beat faster

triggers the blood vessels to contract and direct blood toward major muscle groups

contracts muscle cells below the surface of the skin to stimulate perspiration

binds to receptors on the pancreas to inhibit the production of insulin

The bodily changes that occur as adrenaline circulates throughout the blood is commonly called an adrenaline rush because these changes happen rapidly. In fact, they happen so fast that you might not even fully process what is happening.

The rush of adrenaline is what gives you the ability to dodge out of the way of an oncoming car before you’ve had a chance to even think about it.

Activities that cause adrenaline rush

Although adrenaline has an evolutionary purpose, some people take part in certain activities just for the adrenaline rush. Activities that can cause an adrenaline rush include:

watching a horror movie

skydiving

cliff jumping

bungee jumping

cage diving with sharks

zip lining

white water rafting

What are the symptoms of an adrenaline rush?

An adrenaline rush is sometimes described as a boost of energy. Other symptoms include:

rapid heart rate

sweating

heightened senses

rapid breathing

decreased ability to feel pain

increased strength and performance

dilated pupils

feeling jittery or nervous

After the stress or danger is gone, the effect of adrenaline can last up to an hour.

Adrenaline rush at night

While the fight-or-flight response is very useful when it comes to avoiding a car accident or running away from a rabid dog, it can be a problem when it’s activated in response to everyday stress.

A mind full of thoughts, anxiety, and worry also stimulates your body to release adrenaline and other stress-related hormones, like cortisol (known as the stress hormone).

This is especially true at night when you lie in bed. In a quiet and dark room, some people can’t stop focusing about a conflict that happened that day or worrying about what’s going to happen tomorrow.

While your brain perceives this as stress, real danger isn’t actually present. So this extra boost of energy you get from the adrenaline rush has no use. This can leave you feeling restless and irritable and make it impossible to fall asleep.

Adrenaline may also be released as a response to loud noises, bright lights, and high temperatures. Watching television, using your cellphone or computer, or listening to loud music before bedtime can also contribute to a surge of adrenaline at night.

How to control adrenaline

It’s important to learn techniques to counter your body’s stress response. Experiencing some stress is normal, and sometimes even beneficial for your health.

But over time, persistent surges of adrenaline can damage your blood vessels, increase your blood pressure, and elevate your risk of heart attacks or stroke. It can also result in anxiety, weight gain, headaches, and insomnia.

To help control adrenaline, you’ll need to activate your parasympathetic nervous system, also known as the “rest-and-digest system.” The rest-and-digest response is the opposite of the fight-or-flight response. It helps promote equilibrium in the body, and allows your body to rest and repair itself.

Try the following:

deep breathing exercises

meditation

yoga or tai chi exercises, which combine movements with deep breathing

talk to friends or family about stressful situations so you’re less likely to dwell on them at night; similarly, you can keep a diary of your feelings or thoughts

eat a balanced, healthy diet

exercise regularly

limit caffeine and alcohol consumption

avoid cellphones, bright lights, computers, loud music, and TV right before bedtime

When to see a doctor

If you have chronic stress or anxiety and it’s preventing you from getting rest at night, speak with your doctor or psychologist about anti-anxiety medications, such as selective serotonin reuptake inhibitors (SSRIs).

Medical conditions that cause an overproduction of adrenaline are very rare, but possible. A tumor of the adrenal glands, for example, can overstimulate the production of adrenaline and cause adrenaline rushes.

Additionally, for people with post-traumatic stress disorder (PTSD), memories of the trauma may elevate adrenaline levels after the traumatic event.

What Is Adrenaline?

Adrenaline is a stress hormone known as epinephrine. Produced by the adrenal glands and released into the bloodstream, adrenaline is part of the “fight or flight” response. When facing a perceived stressor or threat, this hormone stimulates the nervous system.

Imagine you’re riding your bike, and a person appears suddenly, causing you to swerve. Your body will produce adrenaline, which leads to an immediate physical reaction. You may sweat, feel your heart racing, or your body shaking. This is a healthy, natural response. When you’re in a dangerous, unsafe, or problematic situation, this adrenaline can help you react quickly.

However, you can experience an adrenaline rush when taking the stage at a crowded stadium, before a competitive sporting event, when you’re on a roller coaster, or if you’re in the middle of an argument, among other situations.

Characteristics

Produced alongside cortisol and aldosterone, adrenaline releases when you’re in a crisis or experiencing a strong emotion like excitement or fear. It happens automatically. When adrenaline is released, messages are sent to different organs in your body, such as the heart and lungs.

When adrenaline is released, you may experience:

Elevated blood pressure

Increased heart rate

Heightened senses

Decreased sensitivity to pain

Enlarged pupils

Shaky limbs

Excessive sweating

When you’re in a “fight-or-flight” situation, you may run faster than you normally would, or you may not feel pain, even if you’ve been injured. This can happen when your body shifts to survival mode.

When you’re in dangerous, unsafe situations, this reaction can help keep you safe. Once the situation has changed and you’re no longer facing a threat or stressor, your body will start to calm down, and the symptoms will subside.

Effects on Body and Mind

Some people love to experience the spike of adrenaline. Bungee jumpers, car racers, and athletes may chase this feeling, pushing themselves beyond their boundaries. For thrill-seekers, adrenaline is addictive.

Too much adrenaline can become a problem, especially if you’re experiencing chronic stress. If you’re perpetually in “fight-or-flight” mode, you're going to experience prolonged symptoms, which can harm your mind and body.

A frequent overload of adrenaline can lead to:

Digestive problems

Headaches

Muscle tension

Insomnia

Weight gain

Anxiety

Depression

High blood pressure

Heart disease

Stroke

Adrenal gland disorders can also occur if you don’t produce enough hormones or produce too many. Pheochromocytoma, for instance, is a tumor that can result from too much adrenaline. This can lead to high blood pressure and other symptoms.

Adjusting Adrenaline Levels

Maybe you work in a high-stress environment, such as a hospital or a school, or you’re dealing with personal stressors, like marital problems, which can cause an overload of adrenaline.

To limit the frequency of adrenaline rushes, you want to address the stressors in your life and practice healthy coping strategies. These could include:

Daily exercise

Meditation

Deep breathing

Mindful rest

Healthy eating

Limiting caffeine or alcohol intake

Prolonged stress is detrimental to your health and well-being, but it can be addressed. If you’re having trouble minimizing the stress in your life, we recommend speaking to a mental health professional who can offer coping strategies or treatment options.

Effective Stress Relievers

Treatment for Anaphylaxis

Adrenaline is used in emergencies to treat a serious allergic reaction, known as anaphylaxis. It can stimulate the heart, relax the muscles in the airways, raise blood pressure, and improve breathing, preventing the progression of life-threatening respiratory or cardiovascular symptoms.1

If you’re allergic to bees and get stung or if you’re allergic to peanuts and eat peanut butter, then you need to inject adrenaline quickly to combat hives, throat swelling, shortness of breath, or other symptoms of anaphylaxis.

Epinephrine Auto-Injector, commonly called an EpiPen, reverses symptoms. However, if it’s not used immediately following an allergic reaction and the individual doesn’t receive medical attention, anaphylaxis can lead to death, so it’s important to keep an EpiPen accessible if you have known allergies.

A Word From Verywell

You may or may not enjoy the feeling of adrenaline, but it’s a natural, human reaction. You shouldn’t avoid certain activities, like public speaking, for the sake of avoiding the anxious feeling of an adrenaline rush, but engaging in risk-taking behaviors can also be problematic.

If you’re an adrenaline junkie, take precautions to protect yourself and those around you. If you’re experiencing too much adrenaline on a frequent basis or you need more coping strategies to deal with an anxiety disorder or other psychological stressors, consider speaking to a therapist.

An adrenaline rush can be life-saving. It can also be overwhelming. If you’re unable to manage your stress or are feeling.

Adrenaline

What is adrenaline?

Adrenaline is a hormone that helps you react very quickly if you are faced with an exciting, stressful or dangerous situation. This is known as the ‘fight-or-flight response’. In this type of situation, your brain sends messages to your adrenal glands (located just above the kidneys) to start releasing the hormone into the blood. You will feel the effects of the adrenaline within 2 or 3 minutes.

Adrenaline is also a medication used to treat a severe allergic reaction (anaphylaxis) in an emergency. It may also be used during cardiac arrest, croup and asthma when other treatments are not effective.

When the situation becomes calmer, the glands stop producing adrenaline. You might still feel the effects of it though, for up to 1 hour.

The dose can be given using an autoinjector, and you can read about how to use an adrenaline autoinjector here. If someone is having an anaphylaxis, give the adrenaline first then call triple zero (000) and ask for an ambulance.

What is the role of adrenaline?

Adrenaline makes your heart beat faster and your lungs breathe more efficiently. It causes the blood vessels to send more blood to the brain and muscles, increases your blood pressure, makes your brain more alert, and raises sugar levels in the blood to give you energy. Your pupils grow larger and you sweat.

When you have a lot of adrenaline in your blood, you don’t feel as much pain, so you can keep running or fighting, even if you are injured. It makes you stronger and allows you to perform better.

The body also produces a similar chemical called noradrenaline (or norepinephrine). It is made in the nervous system and released into the blood continuously. Unlike adrenaline, which affects several parts of the body, noradrenaline’s main role is to control blood pressure.

Noradrenaline is also used to treat people whose hearts have stopped beating (cardiac arrest). It can be used along with other medicines to control pain before or during surgery.

Is having too much or too little adrenaline a problem?

If you have too much adrenaline, it can lead to symptoms including:

dizziness

changes to your vision

a quick heartbeat

feeling irritable and jittery

insomnia

Being stressed can lead to someone having too much adrenaline. Some rare medical conditions, such as a tumour on the adrenal glands, can also cause someone to have too much adrenaline.

Over time, high levels of adrenaline can increase your risk of a heart attack or stroke, and cause heart palpitations, high blood pressure, anxiety and weight loss.

Having too little adrenaline is very rare, but people who don’t have enough of the hormone cannot react properly to stressful situations.

How can I adjust my adrenaline levels?

If you are stressed, you can lower the adrenaline level in your body by:

breathing deeply

meditating

practising yoga or tai chi

It also helps to eat a healthy diet, exercise regularly and limit caffeine and alcohol.

Adrenaline injections

An adrenaline injection, such as EpiPen or Adrenaline Mylan, is used as a treatment for a severe allergic reaction (anaphylaxis). It works by quickly reducing swelling in the throat, opening up the airways and preventing the blood pressure from falling too low. It is sometimes used for people who have serious breathing problems including asthma with associated anaphylaxis, croup and cardiac arrest.

The adrenaline is injected into the large muscle in the thigh and can save someone’s life. If in doubt, always use the adrenaline autoinjector first, then use asthma reliever medicine and call triple zero (000) for an ambulance.

There are 2 doses of adrenaline autoinjector available in Australia and New Zealand:

0.3mg adrenaline, for adults and children over 20kg

0.15mg adrenaline, for children 7.5 to 20kg

For more information on adrenaline autoinjectors, including videos on how to use them, visit the ASCIA website.

If you are at risk of anaphylaxis, it is a good idea to discuss an 'anaphylaxis action plan' with your doctor or pharmacist.

The physiology and pharmacology of adrenaline

Physiology of adrenaline

What is adrenaline/epinephrine and how does it differ from noradrenaline/norepinephrine?

Adrenaline is a hormone derived from tyrosine, an amino acid. Adrenaline is also spelt adrenalin, and in North America is known by the name epinephrine. Adrenaline/epinephrine, noradrenaline/norepinephrine and dopamine are classified as catecholamines.

Adrenaline has a methyl group attached to its nitrogen.

Noradrenaline has a hydrogen atom attached to the nitrogen.

Epinephrine and norepinephrine are stress hormones and function as part of the 'fight or flight' response.

Where and how is adrenaline produced and released in the body?

Adrenaline is produced by the chromaffin cells in the medulla of the adrenal glands and is released in response to a stressor or perceived threat. This stressor can be emotional, physical or environmental.

The steps to the adrenaline response and release are as follows:

A stressor is perceived

This stimulates signals to the brain

The brain sends signals to the chromaffin cells of the adrenal glands

Adrenaline is released

What happens to the body when adrenaline is released?

The release of adrenaline activates specific physiological reactions, which are intended to prepare the body to respond to the perceived stressor or threat.

The responses include:

Stimulation of the liver to break down glycogen into glucose (to provide quick energy to the body)

Relaxation of the smooth muscles in the lungs and respiratory tract to enhance inspiration and lung capacity

Stimulation of the beta-adrenergic receptors in the myocardium to increase cardiac contractility and heart rate

Contraction of the arteries in the skin to divert blood flow

Contraction of the smooth muscles in the skin, causing the hairs to raise on the skin surface (goosebumps)

Pharmacology of adrenaline

What is adrenaline used for pharmacologically?

Adrenaline is a first-line treatment for anaphylaxis, an IgE-mediated, severe allergic reaction caused by the release of mediators from mast cells that have been previously sensitised to a specific allergen. Anaphylaxis is characterised by:

Respiratory difficulty due to airway constriction

Urticaria (hives)

Angioedema: usually facial swelling (may also occur in hands and feet)

Hypotension (low blood pressure leading to collapse)

Nausea and vomiting

Due to its physiological effects, adrenaline is able to reverse anaphylaxis by:

Increase of blood pressure through increasing resistance in the peripheral vascular system

Bronchodilation—opening the airways

Decreasing angioedema

Other uses of adrenaline include its use in local anaesthetic to enhance the duration of anaesthesia and to reduce the chance of haemorrhage. It is also used as an adrenergic receptor stimulant during cardiopulmonary resuscitation (CPR).

What are the risks of use of adrenaline?

While adrenaline is considered to be a life-saving medication, there are risk involves with its use, especially if it is administered intravenously or in high dosages. These risks are of particular concern in the following circumstances:

Elderly patients

Patients with a history of ischaemic heart disease, arteriopathies or hypertension (high blood pressure)

Patients on medications such as tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs) and beta-blockers

Prolonged or repeated use of adrenaline has the potential to cause cardiac hypertrophy due to stimulation of mitogen-activated proteins and an increase in myocardial cells.

Adrenaline self-treatment for anaphylaxis

Knowledge of self-administration of adrenaline to treat anaphylactic shock is critical for those with a history of severe allergic reactions. The procedure of self-administering adrenaline using the Epipen® device is as follows:

Open and cap and remove Epipen from its carrier tube

Grip pen so that orange tip is facing downwards and, holding firmly, remove the safety release

Place tip against outer thigh, then push against it at a 90-degree angle. There will be an audible click.

Hold in place for 10 seconds to allow the medication to be delivered.

Remove the EpiPen and massage injection site for an additional 10 seconds.

Seek further emergency care due to the short duration of the adrenaline