Epinephrine

Epinephrine (Adrenalin): Uses, Side Effects, Dosage, and Mechanism of Action

What is Epinephrine?

Epinephrine, also known as adrenaline, is produced by the medulla of the adrenal glands. It is released into the bloodstream in response to strong emotions like fear or anger, causing increased heart rate, blood pressure, muscle strength, and sugar metabolism. Epinephrine has been classified as a sympathomimetic (Adrenergic agonist) catecholamine that uses a G protein-linked second messenger pathway to exert its pharmacologic effects on both alpha-adreno-receptors and beta-adrenoceptors.

What are the main functions of Epinephrine / Adrenaline?

Produced from tyrosine in the medulla of adrenal glands, epinephrine is released with small quantities of norepinephrine into the blood circulation. It causes vasodilation at low doses and at high doses it causes vasoconstriction. The “Flight or Fight Response,” as it is known, prepares the body for vigorous activity. Epinephrine is a stimulant in cardiac arrest, a vasoconstrictor in case of shock, and a bronchodilator and an antispasmodic drug in bronchial asthma.

Mechanism of Action / What does epinephrine do?

In small quantities, it shows a great affinity for beta-adrenoceptors. In large doses, it shows selective affinity towards alpha receptors.

Alpha-1 effects

  • Increase in vascular smooth muscle contraction
  • Contraction of pupillary dilator muscles
  • Contraction of intestinal sphincter muscles

Beta-1 and Beta-2 effects

  • Contraction of the myocardium (beta-1 action, positive inotropic effect)
  • Increase in heart rate
  • Increased renin release
  • Bronchodilation (beta-2 action)
  • Vasodilation (beta-2 action)
  • Production of aqueous humor

Pharmacokinetics of Adrenaline / Epinephrine

How to administer it into the body?

It degrades rapidly, so it has a small duration of action, and the onset of its action is very rapid. To attain the most rapid onset, during emergencies, adrenaline is given via the IV (intravenous) route. Other routes of administration of epinephrine involve the subcutaneous route, intramuscular route, inhalational route, by endotracheal tube, neonatal resuscitation, and topically in the eye.

Can Adrenaline / Epinephrine be given orally?

It is not given orally because its oral administration is ineffective. Intestinal enzymes degrade the drug following an oral administration thus making it useless.

Metabolism

Just like other catecholamines, the metabolism of epinephrine involves two enzymatic pathways:

  1. Monoamine oxidase (MAO)
  2. Catechol-O-Methyl transferase (COMT)

How does it excrete out of the body?

Metabolites of epinephrine are excreted out of the body by urine.

Adrenaline / Epinephrine Uses

Following are the indications for use of epinephrine

  • Anaphylaxis
  • Cardiac arrest (used to bring back cardiac rhythm)
  • To treat open-angle glaucoma (used topically in the form of 2% epinephrine eye drops)
  • Local anesthetic
  • Acute asthma
  • Emergency treatment of type 1 hypersensitivity reactions
  • Hypotension because of septic shock
  • To induce and maintain mydriasis during ocular surgery

Use of Epinephrine in Pregnancy / Is it safe during Pregnancy?

Epinephrine can be used during pregnancy only if the possible benefit outweighs the danger to the fetus. It lies in pregnancy category C drugs. It crosses the placenta. No well-controlled human studies are available for the use of epinephrine. Animal studies have shown some teratogenic effects. Its use in pregnancy requires caution if the patient has high blood pressure i.e. 130/80mmHg or more.

According to American Dental Association, for diagnostic, preventive, and dental treatments, local anesthetics which are available in combination with epinephrine such as Bupivacaine, Lidocaine, and Mepivacaine can be used during pregnancy.

Adrenaline Contraindication

It is contraindicated in patients who have hypersensitivity to adrenergic agonists. Other contraindications of epinephrine may include:

  • Closed-angle glaucoma
  • Anesthesia with Halothane
  • Catecholamine polymorphic ventricular tachycardia
  • Peripheral arterial occlusive vascular disease with thrombosis
  • Ergot poisoning
  • Ventricular fibrillation

Toxicity

Epinephrine toxicity can be potentially lethal in some cases. The overall treatment of toxicity with adrenaline is primarily supportive. Many researchers have reported the use of Labetalol as an antidote to treat epinephrine overdose in certain cases.

Some specific conditions of epinephrine toxicity are given below

Increased beta-1 adrenergic effect

Treatment: Beta adreno-receptor blocking drugs such as Metoprolol

Presser effects

Treatment: Alpha adreno-receptor blocking drugs with respiratory support

Interactions with Other Drugs

Epinephrine shows interaction with the following drugs.

  • Cocaine and cyclic antidepressants
  • Monoamine oxidase inhibitors
  • Beta-blockers
  • Inhalational anesthetics
  • Digitalis
  • Halogenated general anesthetics and cyclopropane
  • Chloral hydrate
  • Catechol-O-Methyl transferase inhibitors
  • Diuretics
  • Anti-hypertensive drugs
  • Vasodilators

Epinephrine Side Effects

It produces the following side effects on various systems in the body:

  • Side effects related to the central nervous system include fear, tension, anxiety, Parkinson’s disease exacerbation, agitation, and tremors.
  • Because of an increase in blood pressure, the drug may cause a hemorrhage.
  • It may induce cardiac arrhythmias, tachycardia, palpitations, and chest pain.
  • The drug can trigger pulmonary edema.
  • Side effects related to the gastrointestinal tract include nausea and vomiting.
  • The drug may cause decreased renal perfusion
  • At the site of injection, epinephrine may result in necrosis on the skin.

Brand Name:

Auvi-Q brand name containing Epinephrine.

References

https://www1.udel.edu/chem/C465/senior/fall00/Performance1/epinephrine.htm.html

Lippincott’s illustrated reviews Pharmacology 4th edition

https://www.ncbi.nlm.nih.gov/books/NBK482160/
https://www.ada.org/en/member-center/oral-health-topics/pregnancy#:~:text=Preventive%2C%20diagnostic%2C%20and%20restorative%20dental,may%20be%20used%20during%20pregnancy.
https://www.drugs.com/pregnancy/epinephrine.html
https://pubmed.ncbi.nlm.nih.gov/2344087/
https://www.rxlist.com/adrenalin-drug.htm
https://accessmedicine.mhmedical.com/content.aspx?bookid=391&sectionid=42070000

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