Epinephrine, also known as adrenalin or adrenaline, is a hormone, neurotransmitter and medication. It is generally produced by both the adrenal glands and certain neurons. It plays an important role in the fight-or-fight response by growing blood flow to muscles, output of the heart, pupil dilation and blood sugar.

EpinephrineJokichi Takamine first isolated epinephrine in 1901. As a medication, it is used to treat a number of conditions, including anaphylaxis, cardiac arrest and superficial bleeding. Inhaled epinephrine may be used to improve the symptoms of croup. 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. 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. The adrenals contribute about 7% of circulating norepinephrine, most of which is a spillover from neurotransmission with little activity as a hormone.

USES OF EPINEPHRINE

Epinephrine during exercise

One physiological stimulus to epinephrine secretion is exercise. This was first demonstrated using the enervated pupil of a cat as an assay, later confirmed using a biological assay on urine samples. Biochemical methods for measuring catecholamine in plasma were published from 1950 onwards. Although much valuable work has been published using fluorimetric assays to measure total catecholamine concentrations, the method is too nonspecific and insensitive to accurately determine the very small quantities of epinephrine 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 epinephrine. Early REA plasma assays indicated that epinephrine and total catecholamine rise late in exercise, mostly when anaerobic metabolism commences. During exercise the epinephrine blood concentration rises partially from increased secretion from the adrenal medulla and partly from decreased metabolism because of reduced hepatic blood flow. Infusion of epinephrine to reproduce exercise circulating concentrations of epinephrine in subjects at rest has little hemodynamic effect, other than a small ß²-mediated fall in diastolic blood pressure. Infusion of epinephrine well within the physiological range suppresses human airway hyper-reactivity sufficiently to antagonize the constrictor effects of inhaled histamine.

Emotional Response

Epinephrine and effects on emotion and fearEvery emotional response has a behavioral component, an autonomic component, and a hormonal component. The hormonal component includes the release of epinephrine, 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 epinephrine is fear. In an experiment, subjects who were injected with epinephrine 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. The findings from this study demonstrate that there are learned associations between negative feelings and levels of epinephrine. Overall, the greater amount of epinephrine is positively correlated with an arousal state of negative feelings. These findings can be an effect in part that epinephrine 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 epinephrine 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’ similar findings were also supported in a study that involved rodent subjects that either were able or unable to produce epinephrine. Findings support the idea that epinephrine does have a role in facilitating the encoding of emotionally arousing events, contributing to higher levels of arousal due to fear.

Memory

It has been found that adrenergic hormones, such as epinephrine, can produce retrograde enhancement of long-term memory in humans. The release of epinephrine due to emotionally stressful events, which is endogenous epinephrine, can modulate memory consolidation of the events, ensuring memory strength that is proportional to memory importance. Post-learning epinephrine activity also interacts with the degree of arousal associated with the initial coding. There is evidence that suggests epinephrine does have a role in long-term stress adaptation and emotional memory encoding specifically. Epinephrine may also play a role in elevating arousal and fear memory under particular pathological conditions including post-traumatic stress disorder. Overall, “Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects.” Studies have also found that recognition memory involving epinephrine depends on a mechanism that depends on p adrenoceptors. Epinephrine does not readily cross the blood-brain barrier, so its effects on memory consolidation are at least partly initiated by ß adrenoceptors in the periphery.

Pathology

Increased epinephrine secretion is observed in phaeochromocytoma, hypoglycaemia, myocardial infarction and to a lesser degree in benign essential familial 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. Therefore, there must be some autonomy of the adrenal medulla from the rest of the sympathetic system.

Measurement in biological fluids

Epinephrine 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 epinephrine concentrations in resting adults are normally less than 10 ng/1, but may increase by 10-fold during exercise and by SO-fold or more during times of stress.

RACEMIC EPINEPHRINE

Breathing is a necessary function in order to stay alive. Racemic epinephrine is commonly used in small children that have severe respiratory conditions. When children have respiratory illness or conditions, it can be serious. The symptoms of conditions racemic epinephrine is used for include chest tightening, wheezing, and severe shortness of breath. Racemic epinephrine can help to open up the airways and restore more normal breathing quickly. Racemic epinephrine is an inhaled bronchodilator that is made from both a bronchodilator and epinephrine mixed together. It is most often used for respiratory conditions that cause the lungs to become tight and closed up. The bronchodilator opens up the airways and the epinephrine helps to keep them open. The epinephrine is also a powerful anti-histamine that helps reduce reactions to certain chemicals in the body that produce the inflammation in the lungs.

Racemic epinephrine is used for the following conditions:

  • Cough in children (moderate to severe cases)
  • Asthma in both adults and children
  • Respiratory Syncytial Virus (RSV)
  • After exudation of a ventilator tube to reduce irritation and stridor

Racemic epinephrine works right away to lower histamines in the body and constrict blood vessels. This eases the blood in an out of the lungs and sends oxygenated blood to the heart and body. It also relaxes the bronchial tubes, opening them up to help the air move through the lungs. This medication is used for relieving the symptoms of bronchial asthma, croup, and respiratory syncytial virus. It may be used for other conditions as directed by your physician.

Nebulized racemic epinephrine can have the following side-effects nervousness, shakiness, tremors, headache, reduced appetite, insomnia, nausea, nervous feelings, dizziness, anxiety, and muscle tension. These side-effects are very common and normal with this medication. Contact the doctor if they are bothersome usually, if one uses this medication less often or smaller dosages the side-effects resolve on their own.

The following are severe side-effects and need immediate medical attention:

  • Signs of allergic reaction – hives, rash, trouble breathing, swelling of face or lips
  • Chest Pain
  • Increased heart rate (over 120)
  • Increased wheezing
  • Increased blood pressure (over 140/90)
  • Mental changes – Hallucinations, agitation, disorientation, or aggressive behavior
  • Complications of these side-effects include cardiac arrhythmia, brain hemorrhage, stroke, and heart attack.

Caution for this medication are:

  • Use care when giving to children less than 12 years old
  • Be careful in people that are sensitive to bronchodilators
  • Use caution with people who are hypertensive or have cardiac disease
  • Do not use if you are taking an MAO inhibitor
  • Do not use with other bronchodilators or space them 4 hours apart
  • Do not take more than the recommended dosage
  • Get medical help right away if breathing issues persist!
  • Do not use if the solution does not look right (discoloration)

There have been instances that people have a reverse effect from this medication and experience worsened symptoms. Also, if the medication is used too often, airways may become more inflamed. If reverse effects or symptoms worsen, discontinue use of the medication and seek medical attention right away. The excessive use of any bronchodilator and adverse effects have caused respiratory failure, cardiac arrest and death in some cases.

EPINEPHRINE PEN (EPIPEN)

EpinephrineUse EpiPen (epinephrine injection, USP) 0.3 mg or EpiPen Jr. (epinephrine injection, USP) 0.15 mg Auto-Injectors immediately when an allergic emergency (anaphylaxis) occurs. Only a healthcare professional should give additional doses of the medication if one needs more than two injections for a single anaphylactic episode. EpiPen® or EpiPen Jr® should only be injected into the middle of one’s outer thigh (upper leg), through clothing if necessary. Do not inject into veins, buttocks, fingers, toes, hands or feet. Hold the leg of young children firmly in place before and during injection to prevent injuries. In case of accidental injection, seek immediate medical treatment.

Rarely, patients who have used EpiPen® or EpiPen Jr® may develop an infection at the injection site within a few days. Some of these infections can be serious. Call the healthcare professional right away if one has any of the following at an injection site: redness that does not go away, swelling, tenderness, or the area feels warm to the touch. Inform healthcare professional about all of medical conditions, especially if one has asthma, a history of depression, thyroid problems, Parkinson’s disease, diabetes, high blood pressure or heart problems, have any other medical conditions, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Be sure to also tell healthcare professional all the medicines taken, especially medicines for asthma. If one has certain medical conditions, or take certain medicines, condition may get worse or one may have longer lasting side effects when one uses EpiPen® or EpiPen Jr®. Common side effects include fast, irregular or “pounding” heartbeat, sweating, nausea or vomiting, breathing problems, paleness, dizziness, weakness, shakiness, headache, feelings of over excitement, nervousness or anxiety. These side effects usually go away quickly if one lies down and rest. Let the healthcare professional know if there is any side effect that bothers or that does not go away.