ADRAZ

Indications

• Anaphylaxis
• Severe asthma exacerbations
• Cardiac arrest
• Bradycardia
• Hypotension during shock
• Local anesthetic adjunct
• Croup

Dosage

Adults: Refer to the BNF for specific dosing guidelines. Commonly, for anaphylaxis, 0.5 mg (0.5 mL of 1:1000 solution)

Mechanism of action

Epinephrine acts on alpha and beta-adrenergic receptors. It minimizes vasodilation and increases vascular permeability during anaphylaxis, thereby preventing hypotension. By relaxing bronchial smooth muscle and acting as a histamine antagonist, it alleviates symptoms of allergic reactions. The rise in blood pressure results from increased myocardial contractility (positive inotropic effect), increased heart rate (positive chronotropic effect), and vasoconstriction in various vascular beds.

Pharmacodynamics

Epinephrine is a sympathomimetic agent that mimics sympathetic nervous system actions, leading to increased heart rate, enhanced myocardial contractility, and bronchodilation via beta-2 receptors. It is effective in treating bronchospasm, wheezing, and dyspnea, particularly during anaphylactic reactions. It also reduces symptoms of croup when nebulized. Additional effects include alleviating pruritus and urticaria, and relaxing smooth muscle in the gastrointestinal and genitourinary tracts.

Pharmacokinetics

Epinephrine is rapidly absorbed and has a short half-life, typically requiring repeated doses in emergencies. It is metabolized primarily by monoamine oxidase and catechol-O-methyltransferase in the liver and other tissues. The onset of action is usually within minutes when administered intravenously or intramuscularly. Its effects can last from a few minutes to several hours depending on the route of administration.

Contra-indications

• Hypersensitivity to adrenaline or any of the excipients
• Narrow-angle glaucoma
• Acute pulmonary edema
• Severe organic heart disease
• Cardiovascular disorders

Adverse effects

• Tachycardia
• Hypertension
• Anxiety
• Palpitations
• Headache
• Nausea
• Vomiting
• Tremors
• Dizziness
• Respiratory difficulty
• Skin reactions

Interactions

• Beta-blockers: Unknown (increases risk of hypertension and bradycardia)
• Entacapone: Unknown (increases risk of cardiovascular adverse effects)
• Opicapone: Unknown (increases risk of cardiovascular adverse effects)
• Tolcapone: Unknown (increases effects)

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor blood pressure and heart rate during administration
• Be cautious in patients with diabetes mellitus as it may increase blood sugar levels
• Not recommended for use during labor due to potential uterine relaxation

Pregnancy

Adrenaline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Adrenaline is excreted in breast milk, use caution when administering to nursing mothers.

Storage

Store at room temperature, protect from light. Do not freeze.

Formulations

• Injection solution
• Inhalation solution
• Auto-injector

Mechanism of action

Epinephrine acts on alpha and beta-adrenergic receptors. Epinephrine acts on alpha and beta receptors and is the strongest alpha receptor activator. Through its action on alpha-adrenergic receptors, epinephrine minimizes the vasodilation and increased the vascular permeability that occurs during anaphylaxis, which can cause the loss of intravascular fluid volume as well as hypotension. Epinephrine relaxes the smooth muscle of the bronchi and iris and is a histamine antagonist, rendering it useful in treating the manifestations of allergic reactions and associated conditions. This drug also produces an increase in blood sugar and increases glycogenolysis in the liver. Through its action on beta-adrenergic receptors, epinephrine leads to bronchial smooth muscle relaxation that helps to relieve bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis. The mechanism of rise in blood pressure ... is threefold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), vasoconstriction in many vascular beds, especially in precapillary resistance vessels of skin, mucosa, and kidney, along with marked constriction of veins. ... Epinephrine affects respiration primarily by relaxing bronchial muscle. It has a powerful bronchodilator action, most evident when bronchial muscle is contracted because of disease, as in bronchial asthma, or in response to drugs or various autacoids. In such situations, epinephrine has a striking therapeutic effect as a physiological antagonist to substances that cause bronchoconstriction. The beneficial effects of epinephrine in asthma also may arise from inhibition of antigen-induced release of inflammatory mediators from mast cells, and to a lesser extent from diminution of bronchial secretions and congestion within the mucosa. Inhibition of mast cell secretion is mediated by beta2 receptors, while the effects on the mucosa are mediated by alpha receptors The electrophysiologic effects of circulating epinephrine in humans were examined in four study groups of 10 subjects each. In 10 subjects without structural heart disease (Group 1) and in 10 patients with coronary disease or dilated cardiomyopathy (Group 2) epinephrine infusion at 25 and 50 ng/kg body weight per min for 14 min resulted in an elevation of the plasma epinephrine concentration in the physiologic range. In both groups it produced a dose-dependent decrease in the effective refractory period of the atrium, atrioventricular node and ventricle and improvement in atrioventricular node conduction. Epinephrine facilitated the induction of sustained ventricular tachycardia in 3 of the 20 subjects. In Group 3, a beta-adrenergic blocking dose of propranolol was added to the infusion of 50 ng/kg per min of epinephrine. Propranolol not only reversed the effects of epinephrine, but also lengthened these variables compared with baseline values. In group 4, propranolol was administered first, followed by 50 ng/kg per min of epinephrine. Propranolol alone slowed atrioventricular node conduction and mildly prolonged the refractory periods. In the presence of beta-blockade, epinephrine had no effect on atrioventricular node properties but resulted in a lengthening of the atrial and ventricular effective refractory periods. In conclusion, epinephrine in physioloic doses shortens the effective refractory period of the atrium, atrioventricular node and ventricle, improves atrioventricular node conduction and may facilitate the induction of sustained ventricular tachycardia. The overall electrophysiologic effects of epinephrine result from stimulation of beta-receptors. Stimulation of alpha-receptors by epinephrine has no effect on the atrioventricular node but prolongs the effective refractory period of the atrium and ventricle, partially offsetting the shortening of refractory periods mediated by beta-receptor stimulation. Epinephrine

Pharmacodynamics

Epinephrine is a sympathomimetic drug. It causes an adrenergic receptive mechanism on effector cells and mimics all actions of the sympathetic nervous system except those on the facial arteries and sweat glands. Important effects of epinephrine include increased heart rate, myocardial contractility, and renin release via beta-1 receptors. Beta-2 effects produce bronchodilation which may be useful as an adjunct treatment of asthma exacerbations as well as vasodilation, tocolysis, and increased aqueous humor production. In croup, nebulized epinephrine is associated with both clinically and statistically significant transient reduction of croup symptoms 30 minutes post-treatment. Epinephrine also alleviates pruritus, urticaria, and angioedema and may be helpful in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxing effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladder.