Adrenaline, also known as Epinephrine, is a hormone secreted by the medulla of the adrenal glands and was the first hormone to be discovered and obtained in pure form. A hormone is a substance produced by the cells of the body that circulates in the blood; It continues to circulate until it reaches a part of the body where it influences the activity of the cells in that part of the body. Epinephrine is continuously produced in small amounts by the medulla of the adrenal glands. In times of danger, excitement or emotional stress, the brain sends a message to the adrenal glands to increase the rate of epinephrine produced. This increase in epinephrine leads to an increase in heart rate and blood pressure, constriction of small blood vessels, release of sugar stored in the liver and relaxation of certain involuntary muscles while others contract. These responses to the increase of epinephrine prepare the body for the “fight or flight” response. This means the body is physically stronger, more alert and has a greater amount of energy. Therefore, the person is now more prepared to face the danger (fight) or to escape from the danger or stress (flight). In this essay, I will be discussing the history and discovery of epinephrine, the structure and applications in more detail as well as look at what the advantages and disadvantages of epinephrine are. I will finish off my report with discussing the importance of epinephrine in the world today.
History and Discovery
Physicians began to experiment with the adrenal glands in the 1800s. George Oliver, in 1893, experimented on his own son to study the impact glycerol extracts had on the arteries. His son swallowed the adrenal gland of a sheep and results showed that his vessels had constricted. George went to Edward Schäferhad in London where they injected some of the suprarenal extract into a vein of a cat where they also observed a change in diameter. They discovered that the blood pressure increased when extractions of the secretion of the adrenal glands were injected into the cat. Both George Oliver and Edward Schäferhad attempted to isolate and, thus, understand the nature of the substance present in their extract better. in 1897, John Jacob Abel and Albert C. Crawford, had thought they were successful in extracting epinephrine. However, they later discovered that they had extracted a benzoyl derivative instead rather than the pure hormone. It was Jokichi Takamine who was successful in isolating and purifying epinephrine from animal glands; this made epinephrine the first hormone to be extracted in it’s pure state., The chemical formula of epinephrine was correctly discovered by Thomas Aldrich. John Jacob Abel felt deceived about the fact that Takamine had isolated epinephrine. Abel was acceptant of the fact that Takamine had indeed isolated a crystalline product, however, he refused to believe that the product was pure and that the chemical formula proposed by Aldrich was correct. Abel was wrong about the chemical formula of epinephrine but was correct about the fact that Takamine’s epinephrine was impure. Taking the chemistry of that time into consideration, it was difficult to demonstrate that the product was impure. The contaminant was found to be norepinephrine; the product that was sold under the trade name of adrenaline was in fact a mixture of epinephrine and norepinephrine.
Structure
Epinephrine is a hormone as well as a phenethylamine (an amine, that is naturally occurring, which contains one amino group that is connected to an aromatic ring by a two-carbon chain.) Epinephrine falls under the category of a class of compounds called catecholamine, these are water soluble and so circulate in the bloodstream.
Structure of epinephrine
Epinephrine as well as dopamine are the most abundant catecholamines. The action and response that epinephrine can give depends on which adrenergic receptor it binds to.
If epinephrine binds to the 1 receptors of the liver cells, then this will signal the phosphorylation of insulin which will lead to the reduced ability of insulin binding to its receptors. If epinephrine activated the -adrenergic receptors of the muscle and liver cells, then this will increase the process of glycogenolysis. Therefore, epinephrine can lower or raise the blood pressure.
Uses
Epinephrine has many medical uses which includes treating conditions such as a cardiac arrest, Anaphylaxis and superficial bleeding.
In regards to treating a cardiac arrest, epinephrine helps to concentrate the blood around vital organs, the brain and the heart to be specific, by vasoconstriction. To increase the chance of survival, these are the organs that must continue to receive blood. Epinephrine stimulates the cardiac muscle and so strengthens cardiac contractions. This helps to further increase the circulation of blood to the vital organs; this helps to increase the chance of the heart returning to its normal rhythm.
Epinephrine is widely prescribed for anaphylaxis and is considered as the first choice of medication in anaphylaxis; It is an essential medication in the treatment of anaphylaxis as considered by World Health Organization and the World Allergy Organization. In the 1960s, there were several cases of people with anaphylaxis triggered by medications, stinging insects and food. This introduced syringes prefilled with epinephrine to help those without medical training to be able to inject epinephrine readily themselves when in the absence of a healthcare professional. Epinephrine can be administered through various routes, the pros and cons of each of these methods is given in the tables below:
Intramuscular injection
PROS
CONS
- Epinephrine has a vasodilation effect in skeletal muscles
- There are no auto-injector needle lengths favourable for intramuscular injection in obese people.
- The skeletal muscle is vascular (provided with vessels) which leads to rapid absorption
- This is not an effective method if the muscle perfusion (the process of the body delivering blood to a capillary bed) is poor or absent
- Prompt achievement of peak pharmacologic effects
- This is the most commonly recommended route worldwide
Subcutaneous injection
PROS
CONS
- There are readily accessible sites of injection
- Even when epinephrine is diluted it still leads to vasoconstriction of subcutaneous tissue.
- Subcutaneous tissue is poorly vascularized compared to skeletal muscle therefore not as much of a rapid absorption
- The vasoconstrictor effect of epinephrine into subcutaneous tissue slows its own absorption from subcutaneous tissue
Intravenous injection
PROS
CONS
- This is the favourable route of administration for patients who have severe anaphylaxis and have not responded to intramuscular injection of epinephrine. It is also favourable for those who are experiencing hypertension or shock
- To establish a peripheral intravenous route may for the administration of epinephrine may be difficult for the patients whom this method is favourable for.
- Narrower benefit-to-risk ratio than epinephrine administered via other routes.
Pharmacology of epinephrine
Beneficial effects:
- Via the alpha-1 adrenergic receptors there is vasoconstriction, increased blood pressure, relief of shock and hypotension and increased peripheral vascular resistance.
- Decreased insulin release through the alpha-2 adrenergic receptors
- Increased heart rate via the beta-1 adrenergic receptors
- Vasodilation, bronchodilations and decreased release of mediators (histamine, tryptase etc.) through the beta-2 adrenergic receptors
Adverse effects:
- Headaches and pallor through the alpha-1 adrenergic receptors
- Palpitations through the beta-1 adrenergic receptors
- Anxiety via the central nervous system
Intrinsic limitations:
- Epinephrine cannot be taken orally; this is because swallowed epinephrine is metabolized in the wall of the gastrointestinal tract
- Epinephrine has a short duration of action regardless of the route of administration.
- Epinephrine also has a narrow therapeutic index. This means that its benefits cannot be separated from its adverse effects
- Epinephrine also has biphasic pharmacologic effects; a low dose may have the opposite effect than what is intended and may lead to vasodilation and increased release of mediators.
- Solutions of epinephrine have a short shelf-life. Epinephrine in solution breaks down to inactive substances over time.
Epinephrine affects several receptors in the body. Some of the effects that epinephrine has on the body receptors are:
- Vasoconstriction occurs; this increases the blood pressure and, also, helps to decrease swelling.
- The heart rate and the contraction of the heart increases; this can help to prevent cardiovascular collapse or even reverse it.
- The muscles around the airways in the lungs relax, this helps to open the airways up.
- Epinephrine also helps to prevent the release of any additional chemicals that may be allergic. This helps to aid in prevention of further progression of the reaction.
The main reason epinephrine is the number one choice for the medication in the treatment of anaphylaxis is because no other medicine acts on as many body systems as epinephrine does.
There are no new medications available for the treatment of acute anaphylaxis. The World Allergy Organization and The World Health Organization state that the injection on epinephrine is fundamentally important in the treatment of anaphylaxis. It is not possible to conduct randomized placebo-controlled trials of epinephrine in anaphylaxis due to ethical reasons.
Epinephrine can also be injected along with emergency medical treatment in the treatment of life-threatening allergic reactions. These allergic reactions can be caused by stings or insect bites, medications, food, latex etc. Epinephrine works by constricting the blood vessels and causing the relaxing of the muscles in the airways. These effects can reverse extreme low blood pressure, severe skin itching, wheezing or other symptoms of an allergic reaction.
The injection of epinephrine can cause side effects; these can be:
- Redness of the skin, swelling, warmth or tenderness at the site of injection
- Irregular or fast heartbeat
- Nausea and vomiting
- Dizziness
- Anxiety or nervousness
- Pale skin
- Headaches
- Weakness
- Uncontrollable shaking of part of your body
Historically, epinephrine was also used to treat Bronchial asthma and hypoglycemia. However, other drugs are now preferred over epinephrine.
Study comparing epipen (Epinephrine) as an alternative to glucagon in the treatment of hypoglycemia in children with diabetes
Parenteral glucagon is an effective treatment method for hypoglycemia, however, it is difficult to use. One of the side effects of using glucagon is severe nausea. It is also no adapted for use in the school environment as glucagon can be administered only by a licensed health professional.
Ten children who had type 1 diabetes were studied. The average age of the children was 11.7 ± 2.4 years. The average duration of having diabetes was 46 ± 22 months. The study had the approval of the Yale Human Investigation Committee and all the children had the written consent of their parents to carry out the study.
Each child was studied on two occasions with an interval of at least 4 weeks in between the two occasions. On the night before the study, the patient was at the Yale Children’s Clinical Research Centre at 8 pm, had eaten dinner and had also received a bolus of lispro insulin for the meal. An intravenous cannula was inserted for blood sampling; blood glucose levels were measured overnight on an hourly basis and were maintained between the 3.9 and 8.3 mmol/l. If the levels were below 3.9 mmol/l then an intravenous bolus of 20 % dextrose was given. If the levels were greater than 8.3 mmol/l then there was an increase in insulin.
At 7 am the following morning, blood samples were taken. The blood glucose concentration was decreased to 2.8 mmol/l and either 1.0 mg of glucagon or 0.3 mg of epinephrine, via epipen, was given intramuscularly. The patients were then studied for an hour with blood glucose levels being measured in 10 minute intervals. Symptoms of hypoglycemia were also assessed at intervals of 15 minutes by the means of a questionnaire where the patients were asked to give their symptoms a ranking on a scale of 0 to 6. Neither the investigator nor the patient were aware of the drug that was given to them to keep the study random.
Results from the study carried out showed that:
- The time taken to induce hypoglycemia was similar in both studies.
- The plasma glucagon levels were similar with both glucagon and epinephrine.
- Both groups (epinephrine and glucagon) had experienced mild symptoms of hypoglycemia. However, those who had received epinephrine had a higher score for experiencing the symptoms of hypoglycemia. In regards to severe nausea, none of the patients experienced it immediately after receiving glucagon. 9 of the 10 patients did complain of severe nausea 2-6 hours after receiving the glucagon. 9 out of 10 patients also complained that the nausea lasted up to 12 hours.
This led to the conclusion that:
Epinephrine that was injected intramuscularly via Epipen was tolerated better by the children that intramuscular injection of glucagon. Only mild symptoms of hypoglycemia were reported with epinephrine. However, the epinephrine injection was less effective than the glucagon injection in regards to reversing hypoglycemia. The epinephrine injection did decrease the glucose levels but did not reverse hypoglycemia. This shows that a single dose of the epipen is not an adequate alternative to glucagon in treatment of hypoglycemia.
Conclusion
To conclude my report, epinephrine is an important drug in the world today. It is used in the treatment of many conditions; Cardiac arrest, anaphylaxis, severe allergies and superficial bleeding to name a few. Epinephrine has also been compared with other drugs to be used as alternatives for treatment of conditions such as hypoglycemia. Although, epinephrine may not be as effective in these cases in comparison to other drugs it is still worthwhile having that alternative. Not only is epinephrine important as a drug as an extract but also to help prepare our bodies for ‘fight or flight’ situations.