Pharmacology of Adrenaline

Adrenaline, also known as epinephrine, is a vital hormone and neurotransmitter released by the adrenal medulla, primarily in response to stressful scenarios. Its crucial role in the “fight-or-flight” response prepares the body to confront or flee from potential threats. Below is an in-depth exploration of the pharmacology of adrenaline:

Mechanism of Action

Adrenaline is an alpha and beta-adrenergic agonist, exerting most of its effects through beta receptor agonistic action. It increases heart rate (positive chronotropic effect), the force of each contraction (positive inotropic effect), and cardiac output, besides improving coronary blood flow. It also dilates bronchioles, aiding respiration, especially in distress situations. Moreover, it acts on alpha receptors in the skin, mucous membranes, and viscera to cause vasoconstriction which can enhance the effects of local anaesthetics by reducing their absorption, localizing, and prolonging anesthesia duration​¹​.

Pharmacokinetics

Upon subcutaneous or intramuscular administration, adrenaline is well-absorbed with its action onset ranging from immediate to 15 minutes based on the administration route. It is distributed throughout the body and metabolized into inactive metabolites in sympathetic nerve endings, liver, and other tissues by enzymes like Monoamine Oxidase (MAO) and Catechol-O-Methyl Transferase (COMT). The metabolites and conjugates are then excreted through the urine. Adrenaline has a short half-life of about 5 minutes, with its action duration ranging from a few minutes to several hours depending on the administration route​¹​.

Pharmacological Actions

Cardiac Effects: Adrenaline increases heart rate by stimulating cardiac beta1 receptors. It’s a positive inotropic (increases heart muscle contractility) and chronotropic (increases heart rate) agent, which results in increased stroke volume, cardiac output, and improved coronary blood flow​¹​.

Respiratory Effects: It dilates the bronchioles by stimulating beta2 receptors, which can be crucial during respiratory distress​²​.

Vascular Effects: It can increase systolic and mean blood pressure​¹​.

Pharmacodynamics

Adrenaline’s effects include positive inotropy and chronotropy (via Beta-1 receptor stimulation), vasoconstriction (via Alpha-1 receptor stimulation), and skeletal muscle vasodilation (via Beta-2 receptor stimulation). It also increases glycogenolysis, allowing for a rapid energy release. The drug’s effects can be influenced by factors like body weight; higher body weight has been associated with higher plasma adrenaline clearance and a lower concentration plateau​​​³​.

Therapeutic Uses and Administration

Adrenaline finds extensive application in various medical settings like treating anaphylaxis, bronchospasm, and cardiac arrest. The dosage and administration vary based on the condition being treated. For instance, in bronchospasm, an initial dose of 0.1 to 0.5mg may be administered subcutaneously or intramuscularly, with repeated dosing as required at intervals of 10 to 15 minutes​¹​.

Adverse Effects and Contraindications

Adverse effects include palpitations, hypertension, tachycardia, ventricular fibrillation, shock, among others. It’s contraindicated in certain conditions like hypersensitivity to the drug, shock (other than anaphylactic shock), angle-closure glaucoma, and during labor, among others​¹​.

Drug Interactions

Adrenaline can interact with several medications, potentially causing adverse effects. For instance, beta-blockers may block the beta-adrenergic effects of adrenaline, leading to hypertension, while cardiac glycosides might make cardiac arrhythmias more likely​¹​.

Medical Applications

Adrenaline is a first-line treatment for anaphylactic reactions, treats bronchospasm and asthma by dilating bronchioles, restores cardiac rhythm in cardiac arrest cases, controls bleeding by causing local vasoconstriction, enhances the effects of local anesthetics, alleviates nasal congestion as a decongestant, treats open-angle glaucoma, and manages other hypersensitivity reactions besides anaphylaxis​^4, ​​¹​.

The administration, dosage, and drug interactions of adrenaline should be meticulously managed under healthcare professionals’ guidance due to its potent effects on various body systems.