Adrenaline is a naturally occurring sympathomimetic hormone and neurotransmitter which acts on nearly all body tissues. Its actions vary by tissue type and tissue expression of adrenergic receptors. For example, high levels of adrenaline cause 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 subtype’s α1, α2, β1, β2, and β3.
Adrenaline binds to the adrenergic receptors that effects various tissues dependant on the types and expression of specific forms of adrenergic receptors.
- Binding to the receptor α2 inhibits insulin secretion, stimulating glycogenesis in the liver and muscles.
- Binding to the receptor β1 triggers glucagon secretion in the pancreas increasing blood glucose levels and fatty acids.
Adrenaline stimulates glycogenosis in the liver as well as having significant effects of cardiovascular system; it increases heart rate, contractility and conduction across the AV node.
- Transient and minor side effects including anxiety, headache, fear, and palpitations may occur with therapeutic doses of adrenaline, especially in hyperthyroid individuals.
- Repeated local injections may result in necrosis at sites of injection due to vascular constriction.
- May inadvertently induce high arterial blood pressure, resulting in angina pectoris (especially when coronary insufficiency is present), cardiac ischemia, or aortic rupture. Adrenaline may cause serious cardiac arrhythmias in patients not suffering from heart disease and patients with organic heart disease receiving drugs that sensitize the cardiac muscle. With the injection of Adrenaline 1:1,000, a paradoxical but transient lowering of blood pressure, bradycardia and apnoea may occur immediately post-injection.
- Overdosage or accidental IV administration may lead to cerebrovascular hemorrhage resulting from the sharp rise in blood pressure
Parenterally administered Adrenaline initially may produce constriction of renal blood vessels and decrease urine formation. High doses may cause complete renal shutdown.
Since Adrenaline is a strong vasoconstrictor, accidental injection into the digits, hands or feet may lead to the loss of blood flow to the affected area.
- Ischaemic heart disease
- Do not walk patient post adrenaline administration
- If indicated, adrenaline is not withheld because of concerns regarding drug interactions.
- Transient bradycardia followed by tachycardia
- Cardiac arrhythmias
- Kidney failure
- Metabolic acidosis
Pharmacokinetics
- Parenteral administration (IV, IM, SC) generally results in rapid absorption. However, IV delivery is for obvious reasons the quickest method of delivery, resulting in immediate effects.
- IM absorption is less rapid, but is much faster than subcutaneous injection, which tends to result in vasoconstriction at the site and therefore a reduction in blood flow.
- Following IV administration, adrenaline disappears rapidly from the blood stream. Subcutaneously or IM administration results in a rapid onset and short duration of action with effects noticable within 5 to 10 minutes, and maximal effects observable within 20 minutes.
- Adrenaline is rapidly metabolised by an enzyme called Catechol-O-methyltransferase (COMT) which is one of several enzymes that degrade catecholamines such as adrenaline. It is then taken up into extra neuronal tissue in the liver and further metabolised into vanillylmandelic acid (VMA).
- VMA is the major urinary metabolite excreted by the kidneys.
Pharmacodynamics
- Increased cardiac contraction (positive inotropic effects), resulting in more complete emptying of the ventricles. In Ventricular fibrillation, adrenaline increases fibrillation vigour and helps to promote successful defibrillation.
- Increased cardiac rate (positive chronotropic effects) due to increased rate of membrane depolarisation
- Improved Atrioventricular conduction (positive dromatropic effect)
- In large doses adrenaline activates the alpha receptors in the peripheral vascular system and which increases peripheral resistance and therefore increases blood pressure
- Relaxation of smooth muscle
- Powerful bronchodilator relieving respiratory distress due to bronchospasm
- Adrenaline has a plasma half-life of around 2 minutes and duration of action of around 5-10 minutes.
- IV effects are very rapid, approximately 30 seconds, with peak effect within 3-5 minutes.
- Nebulised administration (croup) can see an onset of 1-5 minutes
- IM onset is variable and can be delayed due to local vasoconstriction but is generally within 30-90 seconds
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