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:

1. A stressor is perceived
2. This stimulates signals to the brain
3. The brain sends signals to the chromaffin cells of the adrenal glands
4. 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